Publications by authors named "Kazım Şahin"

160 Publications

Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice.

Neurotox Res 2021 Jun 15. Epub 2021 Jun 15.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

Previous studies revealed that oxidative stress and inflammation are the main contributors to secondary injury after traumatic brain injury (TBI). In an earlier study, we reported that lutein/zeaxanthin isomers (L/Zi) exert antioxidative and anti-inflammatory effects by activating the nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, its precise role and underlying mechanisms were largely unknown after TBI. This study was conducted to investigate the potential mechanism of L/Zi isomers in a TBI model induced by a cold injury model in mice. To investigate the effects of L/Zi, male C57BL/6j mice-induced brain injury using the cold trauma model was allocated into two groups (n = 7): (i) TBI + vehicle group and (ii) TBI + L/Zi group (20 mg/kg BW). Brain samples were collected 24 h later for analyses. L/Zi given immediately after the injury decreased infarct volume and blood-brain barrier (BBB) permeability; L/Zi treatment also significantly reduced proinflammatory cytokines, including interleukin1 beta (IL-1β), interleukin 6 (IL-6), and NF-κB levels and increased growth-associated protein 43 (GAP-43), neural cell adhesion molecule (NCAM), brain-derived neurotrophic factor (BDNF), and Nrf2 levels compared with vehicle control. These data suggest that L/Zi improves mitochondrial function in TBI models, possibly decreasing inflammation and activating the Nrf2 pathway.
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http://dx.doi.org/10.1007/s12640-021-00385-3DOI Listing
June 2021

Wnt signaling pathway activities may be altered in primary Sjogren's syndrome.

Turk J Med Sci 2021 Jun 1. Epub 2021 Jun 1.

Background/aim: Sjögren?s syndrome (SS) is an autoimmune disease and its pathogenesis is still not completely clear. The Wingless (Wnt) / ß - catenin pathway has recently been shown to play an important role in inflammation. This study aims to determine the serum and saliva levels of Dickkopf (DKK)1 and sclerostin and evaluate Wnt-1 and Wnt-3a expression in the salivary gland in patients with primary SS Materials and methods:. This study included 30 patients diagnosed with SS, 30 patients diagnosed with systemic lupus erythematosus (SLE), and 29 healthy controls. Serum and saliva levels of DKK1 and sclerostin were measured and the expressions of Wnt1 and Wnt3a in the salivary gland were measured immunohistochemically.

Results: Serum DKK1 and sclerostin levels were lower in the SS and SLE groups compared to the control group (both p < 0.001). Saliva DKK1 levels were higher in the SS group compared to the control and SLE groups (p = 0.004 and p = 0.009, respectively). Wnt1 and Wnt3a expression were found in salivary gland tissue samples in 71.4% of primary SS patients and relatively frequent than control group.

Conclusions: Serum DKK1 and sclerostin levels in primary SS and SLE were decreased. Moreover, levels of Wnt1 and Wnt3a expression in the salivary gland were also elevated in primary SS. Therefore, it can be concluded that the Wnt / ß - catenin pathway activities may be altered in case of glandular inflammation.
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http://dx.doi.org/10.3906/sag-2102-367DOI Listing
June 2021

L-Carnitine Tartrate Downregulates the ACE2 Receptor and Limits SARS-CoV-2 Infection.

Nutrients 2021 Apr 14;13(4). Epub 2021 Apr 14.

Institut de Recherche Clinique de Montreal, Montreal, QC H2W1R7, Canada.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for one of the worst pandemics in modern history. Several prevention and treatment strategies have been designed and evaluated in recent months either through the repurposing of existing treatments or the development of new drugs and vaccines. In this study, we show that L-carnitine tartrate supplementation in humans and rodents led to significant decreases of key host dependency factors, notably angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), and Furin, which are responsible for viral attachment, viral spike S-protein cleavage, and priming for viral fusion and entry. Interestingly, pre-treatment of Calu-3, human lung epithelial cells, with L-carnitine tartrate led to a significant and dose-dependent inhibition of the infection by SARS-CoV-2. Infection inhibition coincided with a significant decrease in ACE2 mRNA expression levels. These data suggest that L-carnitine tartrate should be tested with appropriate trials in humans for the possibility to limit SARS-CoV-2 infection.
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http://dx.doi.org/10.3390/nu13041297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071056PMC
April 2021

Marine phytoplankton improves recovery and sustains immune function in humans and lowers proinflammatory immunoregulatory cytokines in a rat model.

Phys Act Nutr 2021 Mar 31;25(1):42-55. Epub 2021 Mar 31.

Department of Animal Nutrition, Firat University, Elazig, Turkey.

Purpose: This study investigated the effects of marine phytoplankton supplementation (Oceanix®, Tetraselmis chuii) on 1) maximal isometric strength and immune function in healthy humans following a oneweek high-intensity resistance-training program and 2) the proinflammatory cytokine response to exercise in a rat model.

Methods: In the human trial, 22 healthy male and female participants were randomly divided into marine phytoplankton and placebo groups. Following baseline testing, participants underwent a 14-day supplement loading phase before completing five consecutive days of intense resistance training. In the rat model, rats were randomly divided into four groups (n=7 per condition): (i) control, (ii) exercise, (iii) exercise + marine phytoplankton (2.55 mg/kg/day), or (iv) exercise + marine phytoplankton (5.1 mg/kg/day). Rats in the exercising groups performed treadmill exercise 5 days per week for 6 weeks.

Results: In the human model, marine phytoplankton prevented significant declines in the isometric peak rate of force development compared to placebo. Additionally, salivary immunoglobulin A concentration was significantly lower following the resistance training protocol in the placebo group but not in the marine phytoplankton group. Marine phytoplankton in exercising rats decreased intramuscular levels and serum concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) and intramuscular concentrations of malondialdehyde.

Conclusion: Marine phytoplankton prevented decrements in indices of functional exercise recovery and immune function. Mechanistically, these outcomes could be prompted by modulating the oxidative stress and proinflammatory cytokine response to exercise.
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http://dx.doi.org/10.20463/pan.2021.0007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076584PMC
March 2021

Lutein/zeaxanthin isomers regulate neurotrophic factors and synaptic plasticity in trained rats.

Turk J Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Background/aim: This study was conducted to elucidate the effects of lutein/zeaxanthin isomers (L/Zi) on lipid metabolism on lipid metabolism, oxidative stress, NF-?B/Nrf2 pathways, and synaptic plasticity proteins in trained rats.

Materials And Methods: Wistar rats were distributed into four groups: 1) Control; 2) L/Zi: Rats received L/Zi at the dose of 100 mg/kg by oral gavage; 3) Exercise: 4) Exercise+L/Zi: Rats exercised and received L/Zi (100 mg/kg) by oral gavage. The duration of the study was eight weeks.

Results: Exercise combined with L/Zi reduced lipid peroxidation and improved antioxidant enzyme activities of muscle and cerebral cortex in rats (P < 0.001). In the Exercise + L/ Zi group, muscle and cerebral cortex Nrf2 and HO-1 levels increased, while NF-?B levels decreased (P <0.001). Also, L/Zi improved BDNF, synapsin I, SYP, and GAP-43 levels of the cerebral cortex of trained rats (P < 0.001). The highest levels of BDNF, synapsin SYP, and GAP-43 in the cerebral cortex were determined in the Exercise+L/Zi group.

Conclusion: These results suggested that exercise combined with L/Zi supplementation might be effective to reduce neurodegeneration via improving neurotrophic factors and synaptic proteins, and oxidative capacity in the cerebral cortex.
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http://dx.doi.org/10.3906/sag-2101-264DOI Listing
April 2021

Effects of Exercise Combined with Undenatured Type II Collagen on Endurance Capacity, Antioxidant Status, Muscle Lipogenic Genes and E3 Ubiquitin Ligases in Rats.

Animals (Basel) 2021 Mar 17;11(3). Epub 2021 Mar 17.

Animal Nutrition Department, Veterinary Faculty, University of Firat, 23119 Elazig, Turkey.

The current study aimed to investigate the effect of exercise combined with undenatured type II collagen (UCII) administration on endurance capacity, lipid metabolism, inflammation, and antioxidant status in rats. Twenty-one male Wistar albino rats were divided into three groups as follows: (1) Sedentary control, (2) Exercise (E), (3) Exercise + UCII (4 mg/kg BW/day; E + UCII). The findings showed that the exhaustive running time in the UCII group was significantly prolonged compared to that of the non-supplemented group ( < 0.001). When compared to the control group, total serum cholesterol (TC, < 0.05) and triglyceride (TG, < 0.05) levels decreased, while creatinine kinase (CK) levels increased in the E group ( < 0.001). Serum creatinine kinase levels were reduced in the E + UCII group compared to the E group ( < 0.01). Serum lactate, myoglobin ( < 0.01), and osteocalcin levels ( < 0.01) increased significantly in exercised rats compared to sedentary control rats, while serum lactate ( < 0.01) and myoglobin ( < 0.0001) levels decreased in the E + UCII group compared to control. Additionally, UCII supplementation caused significant increases in antioxidant enzyme activities [SOD ( < 0.01) and GSH-Px ( < 0.05)] and decreases in malondialdehyde (MDA) and tumor necrosis factor (TNF-α) levels ( < 0.001). Muscle lipogenic protein (SREBP-1c, ACLY, LXR, and FAS) levels were lower in the E + UCII group than in other groups. In addition, UCII supplementation decreased muscle MAFbx, MuRF-1, myostatin and increased MyoD levels in exercised rats. Moreover, the E + UCII group had lower muscle inflammatory markers [TNF-α ( < 0.0001) and IL-1β ( < 0.01)] than the control group. These results suggest exercise combined with UCII (4 mg/kg BW/day) modulates lipid, muscle, and antioxidant status in rats.
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http://dx.doi.org/10.3390/ani11030851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002679PMC
March 2021

A Next Generation Formulation of Curcumin Ameliorates Experimentally Induced Osteoarthritis in Rats Regulation of Inflammatory Mediators.

Front Immunol 2021 12;12:609629. Epub 2021 Mar 12.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

Osteoarthritis (OA) is a chronic and debilitating disease of the knee joint. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by an exaggerated inflammation leading to cartilage damage. Currently, no effective and safe therapeutic option capable of restoring articular cartilage tissue and joint architecture is available. We here report a novel and highly bioavailable formulation of curcumin, labeled as Next Generation Ultrasol Curcumin (NGUC), which was 64.7 times more bioavailable than natural 95% curcumin extract as demonstrated in rat bioavailability studies. We further investigated the protective effect of NGUC against monosodium iodoacetate (MIA)-induced knee OA in rats. Analysis of X-ray and histopathological images revealed that NGUC supplementation restored joint architecture and reduced swelling of joints induced by MIA. NGUC treatment caused a significant reduction in the levels of inflammatory mediators such as TNF-α, IL-1β, IL-6, COMP, and CRP, and expressions of MMP-3, 5-LOX, COX-2, and NFκB in synovial tissue of rats with MIA-induced OA. NGUC also decreased serum MDA level and increased the levels of antioxidant enzymes SOD, CAT, and GPX. Thus, our results indicate that a novel formulation of curcumin with enhanced bioavailability effectively ameliorates the pathophysiology of OA.
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http://dx.doi.org/10.3389/fimmu.2021.609629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994281PMC
March 2021

Undenatured Type II Collagen Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rat Model of Osteoarthritis.

Front Vet Sci 2021 4;8:617789. Epub 2021 Mar 4.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group ( < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL ( < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats ( < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.
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http://dx.doi.org/10.3389/fvets.2021.617789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970046PMC
March 2021

Different Doses of -Cryptoxanthin May Secure the Retina from Photooxidative Injury Resulted from Common LED Sources.

Oxid Med Cell Longev 2021 10;2021:6672525. Epub 2021 Feb 10.

Department of Animal Nutrition, Faculty of Veterinary Science, Firat University, Elazig 23119, Turkey.

Retinal damage associated with loss of photoreceptors is a hallmark of eye diseases such as age-related macular degeneration (AMD) and diabetic retinopathy. Potent nutritional antioxidants were previously shown to abate the degenerative process in AMD. -Cryptoxanthin (BCX) is an essential dietary carotenoid with antioxidant, anti-inflammatory, and provitamin A activity. It is a potential candidate for developing intervention strategies to delay the development/progression of AMD. In the current study, the effect of a novel, highly purified BCX oral formulation on the rat retinal damage model was evaluated. Rats were fed with BCX for four weeks at the doses of 2 and 4 mg/kg body weight in the form of highly bioavailable oil suspension, followed by retinal damage by exposing to the bright light-emitting diode (LED) light (750 lux) for 48 hrs. Animals were sacrificed after 48 hours, and eyes and blood samples were collected and analyzed. BCX supplementations (2 and 4 mg/kg) showed improvements in the visual condition as demonstrated by histopathology of the retina and measured parameters such as total retinal thickness and outer nuclear layer thickness. BCX supplementation helped reduce the burden of oxidative stress as seen by decreased serum and retinal tissue levels of malondialdehyde (MDA) and restored the antioxidant enzyme activities in BCX groups. Further, BCX supplementation modulated inflammatory markers (IL-1, IL-6, and NF-B), apoptotic proteins (Bax, Bcl-2, caspase 3), growth proteins and factors (GAP43, VEGF), glial and neuronal proteins (GFAP, NCAM), and heme oxygenase-1 (HO-1), along with the mitochondrial stress markers (ATF4, ATF6, Grp78, Grp94) in the rat retinal tissue. This study indicates that oral supplementation of BCX exerts a protective effect on light-induced retinal damage in the rats via reducing oxidative stress and inflammation, also protected against mitochondrial DNA damage and cellular death.
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http://dx.doi.org/10.1155/2021/6672525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895591PMC
February 2021

Effects of a Novel Magnesium Complex on Metabolic and Cognitive Functions and the Expression of Synapse-Associated Proteins in Rats Fed a High-Fat Diet.

Biol Trace Elem Res 2021 Feb 16. Epub 2021 Feb 16.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, 23119, Elazig, Turkey.

This study was conducted to compare the effects of a novel form of magnesium, Mg picolinate (MgPic), to magnesium oxide (MgO) on metabolic and cognitive functions and the expression of genes associated with these functions in rats fed a high-fat diet (HFD). Forty-two Wistar rats were divided into six groups: control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was supplemented at 500 mg of elemental Mg/kg diet for 8 weeks. MgPic and MgO supplementation decreased visceral fat, serum glucose, insulin, leptin, TC, TG, FFA, testosterone, FSH, LH, SHBG, IGF-1, and MDA levels, but increased brain SOD, CAT, and GSH-Px activities in HFD rats. Inflammation and cognitive-related markers (presynaptic synapsin PSD95, postsynaptic PSD93, postsynaptic GluR1, and GluR2) were improved in HFD rats administered Mg, with more significant effects seen in the MgPic group. MgPic also decreased brain NF-κB but elevated brain Nrf2 levels, compared with the HFD group. The phosphorylation levels of Akt (Thr308), Akt (Ser473), PI3K try 458/199, and Ser9-GSK-3 in the brain were improved after Mg treatment in HFD rats, with more potent effects seen from MgPic supplementation. MgPic has a higher bioavailability and is more effective in improving metabolic parameters and enhancing memory than MgO. The pro-cognitive effects of MgO and MgPic could be mediated via modulation of the AMPA-type glutamate receptor and activation of the PI3K-Akt-GSK-3β signaling pathway. These findings further support the use of MgPic in the management of metabolic and cognitive disorders.
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http://dx.doi.org/10.1007/s12011-021-02619-zDOI Listing
February 2021

Genistein suppresses the inflammation and GSK-3 pathway in an animal model of spontaneous ovarian cancer.

Turk J Med Sci 2021 Feb 8. Epub 2021 Feb 8.

Background/aim: Numerous studies show that cancer risk is reduced by consumption of soy-based foods containing genistein, but its effects on the glycogen synthase kinase-3 pathway (GSK-3) in ovarian cancer is unknown. Therefore, we tested the properties of genistein on inflammatory biomarkers and GSK-3 signaling pathways in the ovaries of old laying hens with ovarian cancer.

Materials And Methods: A total of 300 laying hens were distributed into 3 groups as follows: group 1, animals fed a standard diet (comprising 22.39 mg of genistein/kg of diet); groups 2 and 3, animals fed a standard diet reconstituted with supplementation of 400 mg or 800 mg of genistein/kg of diet, respectively.

Results: Genistein modulated the inflammatory biomarkers by decreasing serum tumor necrosis factor-? (TNF-?), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) compared with control (P < 0.001). Moreover, genistein up-regulated insulin receptor substrate-1 (p-IRS-1) and protein kinase B (p-AKT), but down-regulated GSK-3? and ß after treatment. Genistein acts in a dose-dependent manner.

Conclusion: Genistein exhibited an anticancer effect by reducing pro-inflammatory biomarkers levels and inhibiting GSK-3 expression in the ovaries of old laying hens. Genistein is a potential candidate in the chemoprevention and/or treatment of ovarian cancer.
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http://dx.doi.org/10.3906/sag-2007-254DOI Listing
February 2021

Effects of supplementing different chromium histidinate complexes on glucose and lipid metabolism and related protein expressions in rats fed a high-fat diet.

J Trace Elem Med Biol 2021 May 23;65:126723. Epub 2021 Jan 23.

Research and Development, Nutrition 21, LLC, NY, United States.

Background: The objective of this study was to investigate the effects of different chromium histidinate (CrHis) complexes added to the diet of rats fed a high-fat diet (HFD) on body weight changes, glucose and lipid metabolism parameters, and changes in biomarkers such as PPAR-γ, IRS-1, GLUTs, and NF-κB proteins.

Methods: Forty-two Sprague-Dawley rats were divided equally into six groups and fed either a control, an HFD, or an HFD supplemented with either CrHis1, CrHis2, CrHis3, or a combination of the CrHis complexes as CrHisM.

Results: Feeding an HFD to rats increased body weights, HOMA-IR values, fasting serum glucose, insulin, leptin, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and MDA concentrations as well as AST activities, and decreased serum and brain serotonin concentrations compared with rats fed a control diet (P <  0.0001). The levels of the PPAR-γ, IRS-1, and GLUTs in the liver and brain decreased, while NF-κB level increased, with feeding an HFD (P <  0.05). Although all the CrHis supplements reversed the negative effects of feeding an HFD (P <  0.05), the CrHis1 complex was most effective in changing the protein levels, while CrHisM was most effective in influencing certain parameters such as body weight and serum metabolites.

Conclusion: The results of the present work suggest that the CrHis1 complex is most potent for alleviating the negative effects of feeding an HFD. The efficacy of CrHisM is likely due to the presence of the CrHis1 complex.
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http://dx.doi.org/10.1016/j.jtemb.2021.126723DOI Listing
May 2021

Different Sources of Dietary Magnesium Supplementation Reduces Oxidative Stress by Regulation Nrf2 and NF-κB Signaling Pathways in High-Fat Diet Rats.

Biol Trace Elem Res 2021 Jan 6. Epub 2021 Jan 6.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, 23119, Elazig, Turkey.

Magnesium (Mg) is an essential mineral required for many physiological processes, including ionic balances in ocular tissues. We compared the effects of different Mg-chelates (Mg oxide, MgO vs. Mg picolinate, MgPic) on retinal function in a high-fat diet (HFD) rats. Forty-two rats were divided into six groups and treated orally for 8 weeks as follows: Control, MgO, MgPic, HFD, HFD + MgO, and HFD + MgPic. Mg was administered at 500 mg of elemental Mg/kg of diet. HFD intake increased the levels of retinal MDA and NF-κB, INOS, ICAM, and VEGF but downregulated Nrf2. However, in rats supplemented with MgO and MgPic, the retinal MDA level was decreased, compared with the control and HFD rats. Activities of antioxidant enzymes (SOD, CAT, and GPx) were increased in HFD animals given Mg-chelates (p < 0.001), MgPic being the most effective. Mg supplementation significantly decreased the expression levels of NF-κB, INOS, ICAM, and VEGF in HFD rats while increasing the level of Nrf2 (p < 0.001). Mg supplementation significantly decreased the levels of NF-κB, INOS, ICAM, and VEGF and increased Nrf2 level in HFD rats (p < 0.001), with stronger effects seen from MgPic. Mg attenuated retinal oxidative stress and neuronal inflammation and could be considered as an effective treatment for ocular diseases.
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http://dx.doi.org/10.1007/s12011-020-02526-9DOI Listing
January 2021

Marine Phytoplankton Improves Exercise Recovery in Humans and Activates Repair Mechanisms in Rats.

Int J Sports Med 2020 Dec 22. Epub 2020 Dec 22.

Research Department, Applied Science & Performance Institute, Tampa, United States.

This study investigated the effects of marine phytoplankton supplementation on 1) perceived recovery and ground reaction forces in humans following a non-functional overreaching resistance-training program and 2) myogenic molecular markers associated with muscle cell recovery in a rat model. In the human trial, a 5-week resistance-training program with intentional overreaching on weeks 2 and 5 was implemented. Results indicate that marine phytoplankton prompted positive changes in perceived recovery at post-testing and, while both marine phytoplankton and placebo conditions demonstrated decreased peak and mean rate of force development following the overreaching weeks, placebo remained decreased at post-testing while marine phytoplankton returned to baseline levels. In the rat model, rats were divided into four conditions: (i) control, (ii) exercise, (iii) exercise + marine phytoplankton 2.55 mg·d, or (iv) exercise+marine phytoplankton 5.1 mg·d. Rats in exercising conditions performed treadmill exercise 5 d·wk for 6 weeks. Marine phytoplankton in exercising rats increased positive and decrease negative myogenic factors regulating satellite cell proliferation. Taken together, marine phytoplankton improved perceptual and functional indices of exercise recovery in an overreaching human model and, mechanistically, this could be driven through cell cycle regulation and a potential to improve protein turnover.
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http://dx.doi.org/10.1055/a-1320-1061DOI Listing
December 2020

Status of Novel Coronavirus Disease 2019 (COVID-19) and Animal Production.

Front Vet Sci 2020 5;7:586919. Epub 2020 Nov 5.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

In December 2019, a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that caused severe disease clusters was first reported in Wuhan, the capital of China's Hubei province. This viral disease, which is reported to originate from a seafood market where wild animals are illegally sold, has been transmitted among humans worldwide through close contact. Given the growing number of infected people worldwide and the disastrous consequences in all aspects of life, COVID-19 is a serious public health issue that requires special attention. In some countries, the epidemic curve of infection which was in the plateau phase or decreasing phase during the lockdown period increases day by day since the reopening, indicating the second phase of contamination. Therefore, the preventive measures recommended by the World Health Organization (WHO) must be respected to stop the spread of the disease. The international crisis due to the COVID-19 pandemic negatively affects many sectors, including animal production and its related industries. Indeed, with the cessation of imports and exports between countries, it is not possible to provide feeds that are considered as basic raw materials in livestock raising. This situation impairs animal movements, decreases production inputs availability, and negatively affects the economy. The sustainability of animal production is also affected by a shortage of workers due to the lockdown/curfew, the strong decrease in the purchasing power of the consumer, and the intensification of health care tasks. To prevent contamination of animal products and the spread of the disease with food, the U.S. Centers for Disease Control and Prevention (CDC) recommends frequent disinfection of food and human contact surfaces at production sites using an appropriate antiseptic. The purpose of this review article is to describe the current status of COVID-19 and investigate its effects on animal production. We propose potential approaches to keep animal products processing units and staff safe from SARS-CoV-2 infection and some strategies to improve animal production quantity and economy.
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http://dx.doi.org/10.3389/fvets.2020.586919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676906PMC
November 2020

Rejuveinix Shows a Favorable Clinical Safety Profile in Human Subjects and Exhibits Potent Preclinical Protective Activity in the Lipopolysaccharide-Galactosamine Mouse Model of Acute Respiratory Distress Syndrome and Multi-Organ Failure.

Front Pharmacol 2020 10;11:594321. Epub 2020 Nov 10.

Department of Animal Nutrition, Faculty of Veterinary, Firat University, Elazig, Turkey.

New treatment platforms that can prevent acute respiratory distress syndrome (ARDS) or reduce its mortality rate in high-risk coronavirus disease 2019 (COVID-19) patients, such as those with an underlying cancer, are urgently needed. Rejuveinix (RJX) is an intravenous formulation of anti-oxidants and anti-inflammatory agents. Its active ingredients include ascorbic acid, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate. RJX is being developed as an anti-inflammatory and anti-oxidant treatment platform for patients with sepsis, including COVID-19 patients with viral sepsis and ARDS. Here, we report its clinical safety profile in a phase 1 clinical study (ClinicalTrials.gov Identifier: NCT03680105) and its potent protective activity in the lipopolysaccharide galactosamine (LPS-GalN) mouse model of ARDS. A phase 1, double-blind, placebo-controlled, randomized, two-part, ascending dose-escalation study was performed in participating 76 healthy volunteer human subjects in compliance with the ICH (E6) good clinical practice guidelines to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RJX (Protocol No. RPI003; ClinicalTrials.gov Identifier: NCT03680105). The ability of RJX to prevent fatal shock, ARDS, and multi-organ failure was examined in the well-established LPS-GalN mouse model of sepsis and ARDS. Standard methods were employed for the statistical analysis of data in both studies. In the phase 1 clinical study, no participant developed serious adverse events (SAEs) or Grade 3-Grade 4 adverse events (AEs) or prematurely discontinued participation in the study. In the non-clinical study, RJX exhibited potent and dose-dependent protective activity, decreased the inflammatory cytokine responses (interleukin-6, tumor necrosis factor alpha, transforming growth factor beta), and improved survival in the LPS-GalN mouse model of sepsis and ARDS. Histopathological examinations showed that RJX attenuated the LPS-GalN induced acute lung injury (ALI) and pulmonary edema as well as liver damage. RJX showed a very favorable safety profile and tolerability in human subjects. It shows potential to favorably affect the clinical course of high-risk COVID-19 by preventing ARDS and its complications.
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http://dx.doi.org/10.3389/fphar.2020.594321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683794PMC
November 2020

Clinical Impact Potential of Supplemental Nutrients as Adjuncts of Therapy in High-Risk COVID-19 for Obese Patients.

Front Nutr 2020 22;7:580504. Epub 2020 Oct 22.

Department of Nutrition, School of Veterinary Medicine, Firat University, Elazig, Turkey.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) in China at the end of 2019 caused a major global pandemic and continues to be an unresolved global health crisis. The supportive care interventions for reducing the severity of symptoms along with participation in clinical trials of investigational treatments are the mainstay of COVID-19 management because there is no effective standard therapy for COVID-19. The comorbidity of COVID-19 rises in obese patients. Micronutrients may boost the host immunity against viral infections, including COVID-19. In this review, we discuss the clinical impact potential of supplemental nutrients as adjuncts of therapy in high-risk COVID-19 for obese patients.
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http://dx.doi.org/10.3389/fnut.2020.580504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642511PMC
October 2020

The effects of melatonin against atherosclerosis-induced endothelial dysfunction and inflammation in hypercholesterolemic rats.

Arch Physiol Biochem 2020 Nov 6:1-8. Epub 2020 Nov 6.

Faculty of Medicine, Department of Pharmacology, Firat University, Elazig, Turkey.

The aim of this study was to investigate the effects of melatonin on the serum asymmetric dimethylarginine (ADMA) levels and the expressions of vaspin, visfatin, dimethylarginine dimethylaminohydrolase (DDAH), and signal transducer and activator of transcription-3 (STAT-3) for evaluation of endothelial function and inflammation in the hypercholesterolemic rats. Rats were divided into 5 groups: (1) control, (2) hypercholesterolaemia, (3) melatonin administrated concurrently with cholesterol diet, (4) melatonin administrated only last 2 weeks and fed with cholesterol diet, (5) atorvastatin administered only last 2 weeks fed with cholesterol diet. Although an increase was observed in the expressions of visfatin and STAT-3 and the serum ADMA levels, the vaspin and DDAH protein expressions were found to decrease with hypercholesterolemic diets. Melatonin was determined to restore all the parameters to the normal levels. In conclusion, melatonin may have protective and therapeutic effects on hypercholesterolaemia by regulating vaspin, STAT-3, DDAH, and ADMA signalling pathways and create similar effects with atorvastatin.
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http://dx.doi.org/10.1080/13813455.2020.1838550DOI Listing
November 2020

A Novel Integrated Active Herbal Formulation Ameliorates Dry Eye Syndrome by Inhibiting Inflammation and Oxidative Stress and Enhancing Glycosylated Phosphoproteins in Rats.

Pharmaceuticals (Basel) 2020 Oct 7;13(10). Epub 2020 Oct 7.

Department of Animal Nutrition, Veterinary Medicine, Firat University, Elazig 23119, Turkey.

Dry eye syndrome (DES) is a chronic condition of the eye with insufficient production of tears leading to inadequate lubrication of eyes. Symptoms of DES are associated with discomfort and redness of the eye, blurred vision, and tear film instability which leads to the damaged ocular surface. Inflammation and oxidative stress play a significant role in the pathogenesis of the disease. In this study, the protective effect of different doses (100 or 200 mg/kg) of a novel multi-component oral formulation of lutein/zeaxanthin, curcumin, and vitamin D3 (LCD) was evaluated using a rat model with benzalkonium chloride (BAC)-induced dry eye syndrome. The formulation was administered orally to rats for 4 weeks. We observed a significant improvement in tear volume, tear breakup time, tear film integrity, and reduction in overall inflammation in rats fed with the LCD at dose 200 mg/kg performing better than 100 mg/kg. Furthermore, the formulation helped in lowering oxidative stress by increasing antioxidant levels and restored protective tear protein levels including MUC1, MUC4, and MUC5AC with 200 mg of LCD having the most significant effect. The results strongly suggest that the combination of lutein/zeaxanthin, curcumin, and vitamin-D3 is effective in alleviating the symptoms of dry eye condition with a multi-modal mechanism of action.
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http://dx.doi.org/10.3390/ph13100295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599565PMC
October 2020

Salacia chinensis exerts its antidiabetic effect by modulating glucose-regulated proteins and transcription factors in high-fat diet fed-streptozotocin-induced type 2 diabetic rats.

J Food Biochem 2020 12 5;44(12):e13513. Epub 2020 Oct 5.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

This study aimed to investigate the properties of Salacia chinensis (Celastraceae, SC) and its molecular mechanism in the type 2 diabetic rats. Forty-two Wistar rats were divided into six groups (n = 7): control, SC (100 mg/kg, per os), high-fat diet (HFD), HFD + SC (100 mg/kg), HFD + streptozotocin (STZ, 40 mg/kg, i.p.), and HFD + STZ+SC. SC decreased serum glucose, insulin, triglycerides, free fatty acid, and malondialdehyde levels, but increased serum total antioxidant capacity (0.33 ± 0.02 versus. 0.79 ± 0.03), compared with the untreated group (p < .001). Additionally, SC elevated the expression of glucose-regulated proteins GLUT2, PPAR-ɣ, p-IRS, and Nrf2, but downregulated NF-κB in the liver and kidney (p < .001). In conclusion, SC could improve insulin resistance by modulation of glucose-regulated proteins and transcription factors in diabetic rats. PRACTICAL APPLICATIONS: Present data has contributed to the current ethnomedicinal benefits of SC, through which the SC intake regulated the carbohydrate metabolism and increased the antioxidant capacity. The balance of transcription factors can mediate these efficacies partially and various key proteins involved in energy metabolism, along with oxidative stress and insulin sensitivity.
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http://dx.doi.org/10.1111/jfbc.13513DOI Listing
December 2020

Effects of taurine supplementation on productive performance, nutrient digestibility and gene expression of nutrient transporters in quails reared under heat stress.

J Therm Biol 2020 Aug 1;92:102668. Epub 2020 Aug 1.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, 23119, Turkey.

This study was conducted to examine the effects of dietary taurine supplementation on productive performance, nutrient digestibility, antioxidant status, and the gene expression of ileal nutrient transporters in laying quails reared under heat stress (HS). One hundred and eighty laying Japanese quails (Coturnix coturnix japonica) were fed a basal diet or basal diet supplemented with either 2.5 or 5 g of taurine per kg of diet, and reared at either 22 ± 2 °C for 24 h/d (thermoneutral, TN) or 34 ± 2 °C for 8 h/d (HS) for 12 weeks. The quails reared under HS consumed less feed, produced less egg, and had lower dry matter, organic matter and crude protein apparent digestibilities compared with the quails reared under the TN condition (P = 0.001). However, increasing taurine concentrations in the diet improved feed intake and egg production (P = 0.001), but also the apparent digestibilities (P ≤ 0.027) in quails reared under HS. The greater doses (5 g/kg) of taurine resulted in more responses. The quails reared under HS had greater serum and liver MDA concentrations (P = 0.0001) which decreased with dietary taurine supplementations, particularly greater doses. The gene expressions of ileal PEPT1, EAAT3, CAT1, CAT2, SGLT1, SGLT5, GLUT2, and GLUT5 decreased under HS conditions (P = 0.001). However, supplementing taurine, in a dose-dependent fashion, to the diet of quails reared under HS resulted in increases in the gene expressions of the transporters (P < 0.05) except for CAT1. The results of the present work showed that taurine supplementation, particularly with greater doses (5 g/kg), to the diet of laying quails kept under HS acts as alleviating negative effects of HS, resulting in improvements in productive performance and nutrient digestion, and also upregulation of ileal nutrient transporters.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102668DOI Listing
August 2020

Mango ginger (curcuma amada) inhibits collagen-induced arthritis by modulating inflammatory cytokine levels in rats

Turk J Med Sci 2020 12 17;50(8):2040-2047. Epub 2020 Dec 17.

Department of Animal Nutrition, Faculty of Veterinary Science, Fırat University, Elazığ, TURKEY

Background/aim: Mango ginger (MG: curcuma amada) has antioxidant and antiinflammatory activities. The aim was to evaluate the antiarthritic potential efficacy of MG on collagen-induced arthritis.

Materials And Methods: Twenty-one female Wistar-albino rats were divided into three groups. Arthritis was induced by intradermal injections of type II collagen and Freund’s adjuvant. MG extract was orally administered starting from the first collagen injection. TNF-α, IL-6, IL-17, obestatin, sclerostin, and DKK-1 serum levels were determined, and perisynovial inflammation and cartilage-bone destruction in the paws were histologically evaluated. Moreover, joint tissue TNF-α, IL-17, NF-κB, and COX-2 levels were analyzed.

Results: TNF-α, IL-17, IL-6, and DKK-1 serum levels were increased, and obestatin and sclerostin serum levels were decreased in the arthritis group compared to the control group. However, MG supplements decreased TNF-α, IL-17, IL-6, and DKK-1 serum levels and increased obestatin and sclerostin serum levels. Similarly, while collagen injection increased tissue TNF-α, IL-17, NF-κB, and COX-2 levels, MG decreased TNF-α, IL-17, and NF-κB levels. Moreover, MG ameliorated perisynovial inflammation and cartilage-bone destruction in the paws.

Conclusion: MG ameliorates arthritis via actions on inflammatory ways and wingless (Wnt) signaling pathway. These results suggest that MG may have a considerable potential efficacy for the treatment of rheumatoid arthritis.
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http://dx.doi.org/10.3906/sag-2004-105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775699PMC
December 2020

Phytoplankton Supplementation Lowers Muscle Damage and Sustains Performance across Repeated Exercise Bouts in Humans and Improves Antioxidant Capacity in a Mechanistic Animal.

Nutrients 2020 Jul 4;12(7). Epub 2020 Jul 4.

The Applied Science & Performance Institute, Research Division, Tampa, FL 33607, USA.

The purpose of this study was to investigate the impact of antioxidant-rich marine phytoplankton supplementation (Oceanix, OCX) on performance and muscle damage following a cross-training event in endurance-trained subjects. Additionally, an animal model was carried out to assess the effects of varying dosages of OCX, with exercise, on intramuscular antioxidant capacity.

Methods: In the human trial, endurance-trained subjects (average running distance = 29.5 ± 2.6 miles × week) were randomly divided into placebo (PLA) and OCX (25 mg) conditions for 14 days. The subjects were pre-tested on a one-mile uphill run, maximal isometric strength, countermovement jump (CMJ) and squat jump (SJ) power, and for muscle damage (creatine kinase (CK)). On Day 12, the subjects underwent a strenuous cross-training event. Measures were reassessed on Day 13 and 14 (24 h and 48 h Post event). In the animal model, Wistar rats were divided into four groups ( = 7): (i) Control (no exercise and placebo (CON)), (ii) Exercise (E), (iii) Exercise + OCX 1 (Oceanix, 2.55 mg/day, (iv) Exercise + OCX 2 (5.1 mg/day). The rats performed treadmill exercise five days a week for 6 weeks. Intramuscular antioxidant capacity (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px)) and muscle damage (CK and myoglobin (MYOB) were collected. The data were analyzed using repeated measures ANOVA and -test for select variables. The alpha value was set at < 0.05.

Results: For the human trial, SJ power lowered in PLA relative to OCX at 24 h Post (-15%, < 0.05). Decrements in isometric strength from Pre to 48 h Post were greater in the PLA group (-12%, < 0.05) than in the OCX. Serum CK levels were greater in the PLA compared to the OCX (+14%, < 0.05). For the animal trial, the intramuscular antioxidant capacity was increased in a general dose-dependent manner (E + Oc2 > E + Oc1 > E > CON). Additionally, CK and MYOB were lower in supplemented compared to E alone.

Conclusions: Phytoplankton supplementation (Oceanix) sustains performance and lowers muscle damage across repeated exercise bouts. The ingredient appears to operate through an elevating oxidative capacity in skeletal muscle.
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http://dx.doi.org/10.3390/nu12071990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400322PMC
July 2020

The addition of an amylopectin/chromium complex to branched-chain amino acids enhances muscle protein synthesis in rat skeletal muscle.

J Int Soc Sports Nutr 2020 May 27;17(1):26. Epub 2020 May 27.

Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Firat University, 23119, Elazig, Turkey.

Background: A previous clinical study reported that the addition of an amylopectin/chromium complex (ACr; Velositol®) to 6 g of whey protein (WP) significantly enhanced muscle protein synthesis (MPS). Branched-chain amino acids (BCAAs) are also well-known to enhance MPS. The aim of this study was to determine if the addition of ACr to BCAAs can enhance MPS and activate expression of the mammalian target of the rapamycin (mTOR) pathway compared to BCAAs and exercise alone in exercise-trained rats.

Methods: Twenty-four male Wistar rats were randomly divided into three groups (n = 8 per group): (I) Exercise control, (II) Exercise plus BCAAs (0.465 g/kg BW, a 6 g human equivalent dose (HED)), and (III) Exercise plus BCAAs (0.465 g/kg BW) and ACr (0.155 g/kg BW, a 2 g HED). All animals were trained with treadmill exercise for 10 days. On the day of the single-dose experiment, rats were exercised at 26 m/min for 2 h and then fed, via oral gavage, study product. One hour after the consumption of study product, rats were injected with a bolus dose (250 mg/kg BW, 25 g/L) of phenylalanine labeled with deuterium to measure the fractional rate of protein synthesis (FSR). Ten minutes later, muscle tissue samples were taken to determine MPS measured by FSR and the phosphorylation of proteins involved in the mTOR pathway including mTOR, S6K1, and 4E-BP1.

Results: ACr combined with BCAAs increased MPS by 71% compared to the exercise control group, while BCAAs alone increased MPS by 57% over control (p < 0.05). ACr plus BCAAs significantly enhanced phosphorylation of mTOR, S6K1 and 4E-BP1 compared to exercise control rats (p < 0.05). The addition of ACr to BCAAs enhanced insulin levels, mTOR and S6K1 phosphorylation compared to BCAAs alone (p < 0.05). Serum insulin concentration was positively correlated with the levels of mTOR, (r = 0.923), S6K1 (r = 0.814) and 4E-BP1 (r = 0.953).

Conclusions: In conclusion, the results of this study provide evidence that the addition of ACr to BCAAs significantly enhances exercise-induced MPS, and the phosphorylation of mTOR signaling proteins, compared to BCAAs and exercise alone.
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http://dx.doi.org/10.1186/s12970-020-00355-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251890PMC
May 2020

A Dose-Dependent Effect of Carnipure Tartrate Supplementation on Endurance Capacity, Recovery, and Body Composition in an Exercise Rat Model.

Nutrients 2020 May 23;12(5). Epub 2020 May 23.

Lonza Consumer Health Inc., Morristown, NJ 07960, USA.

The objective of this work is to investigate the effects of Carnipure Tartrate (CT) supplementation with or without exercise on endurance capacity, recovery, and fatigue by assessing time to exhaustion as well as body weight and composition in rats. In addition, antioxidant capacity has been evaluated by measuring malondialdehyde (MDA) levels and antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathioneperoxidase; GSHPx) activities. Fifty-six male Wistar rats were divided into eight groups including seven rats each. A control group did not receive CT nor exercise. Another control group received 200 mg/kg CT without exercise. The other six groups of rats went through an exercise regimen consisting of a 5-day training period with incremental exercise capacity, which was followed by 6 weeks of the run at 25 m/min for 45 min every day. CT was supplemented at 0, 25, 50, 100, 200, and 400 mg/kg per day during the 6 weeks. Rats submitted to exercise and supplemented with CT had a significant and dose-dependent increase in time to exhaustion and this effect seems to be independent of exercise ( < 0.05). Additionally, recovery and fatigue were improved, as shown by a significant and dose-dependent decrease in myoglobin and lactic acid plasma levels, which are two markers of muscle recovery. CT supplementation led to a dose-response decrease in body weight and visceral fat. These effects become significant at 200 and 400 mg/kg doses ( < 0.05). Additionally, the antioxidant capacity was improved, as shown by a significant and dose-dependent increase in SOD, CAT, and GSHPx. Serum MDA concentrations decreased in exercising rats with CT supplementation. CT supplementation led to a decrease in serum glucose, triglycerides, and total cholesterol concentrations with the lowest levels observed at 400 mg/kg dose ( < 0.05). These effects correlated with a significant dose-dependent increase in serum total L-carnitine, free L-carnitine, and acetyl-carnitine, which linked the observed efficacy to CT supplementation. These results demonstrate that CT supplementation during exercise provides benefits on exercise performance, recovery, and fatigue as well as improved the lipid profile and antioxidant capacity. The lowest dose leads to some of these effects seen in rats where 25 mg/kg corresponds to 250 mg/day as a human equivalent.
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http://dx.doi.org/10.3390/nu12051519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284330PMC
May 2020

Effects of walnut oil on metabolic profile and transcription factors in rats fed high-carbohydrate-/-fat diets.

J Food Biochem 2020 07 18;44(7):e13235. Epub 2020 May 18.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.

The aim of this study was to examine the effects of walnut oil (WO) on metabolic profile and transcription factors in rats fed high carbohydrate (HCD) and high-fat diet (HFD). Forty-two male rats were divided in to six groups: (a) Control, (b) WO (20 mg/kg BW), (c) HCD (20% of sucrose), (d) HCD + WO (e) HFD (42% of calories as fat), and (f) HFD + WO. HFD and HCD intake increased final body weights by 19% and 23% and visceral fat weights by 3- and 5-fold, respectively (p < .05 for all). In addition, serum glucose, total cholesterol, triglyceride, and free fatty acids (FFA) insulin, leptin, and MDA levels increased in rats fed with HFD and HCD. WO supplementation improved these metabolic parameters (p < .05 for all). HFD + WO and HCD + WO treated groups had a significant reduction in serum and liver malondialdehyde (MDA) levels by 12% or 15% (p < .05 for both). In addition, WO supplementation lowered the levels of hepatic nuclear factor kappa B (NF-κB) and NADPH oxidase subunit p22 , whereas increased the endothelial-NO synthase (e-NOS), nuclear factor erythroid 2-related factor-2, and sirtuin-1 levels. In conclusion, WO supplementation could alleviate the adverse impacts of both HCD and HFD in the rats. PRACTICAL APPLICATIONS: This study suggests that WO intake can modulate carbohydrate metabolism and increase antioxidant capacity. These properties might be partially mediated through the regulation of the transcription factors and some proteins involved in energy metabolism, as well as a balance of oxidative stress, and insulin sensitivity.
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http://dx.doi.org/10.1111/jfbc.13235DOI Listing
July 2020

Undenatured Type II Collagen (UC-II) in Joint Health and Disease: A Review on the Current Knowledge of Companion Animals.

Animals (Basel) 2020 Apr 17;10(4). Epub 2020 Apr 17.

Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig (+90) 424, Turkey.

OA is quite common in companion animals, especially in large breed dogs and horses. Collagen, the most abundant protein of mammals, has specific connective tissue types for skin, bones, reticulate, basal lamina, bones, cell surfaces, while type II collagen (UC-II) forms the main structure of cartilage tissue. Even at the smaller dosages, UC-II has also been reported to be more effective than the glucosamine and chondroitin sulfate supplements, which are the supplements most frequently used in the market. In this review, we summarize the effects of UC-II on joint health and function in health and disease conditions in companion animals.
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http://dx.doi.org/10.3390/ani10040697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222752PMC
April 2020

Data-Driven identification of chemopreventive agents for breast cancer

Turk J Med Sci 2020 11 3;50(SI-2):1691-1696. Epub 2020 Nov 3.

Division of Hematology-Oncology, Department of Pediatrics and Developmental Therapeutics Program, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA

Preclinical animal models of breast cancer provide the opportunity to identify chemopreventive drugs with single-agent activity as well as effective multi-modality regimens for primary as well as secondary prevention in high-risk persons. Our group has used the 7,12-dimethylbenz(a)anthracene (DMBA) mouse model of carcinogen-induced breast cancer to explore the clinical potential of two tyrosine kinase inhibitors and a nucleoside analog as chemopreventive agents. All three agents exhibited promising preclinical activity both as monotherapy and as components of combination therapy with the standard chemotherapy drug paclitaxel. The tumors developing despite chemoprevention were not only small and grew slowly, but they also displayed a uniquely more pro-apoptotic protein expression profile. Hence, our experimental chemopreventive drugs were capable of preventing the development of aggressive mammary gland tumors with an apoptosis-resistant protein expression profile.
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http://dx.doi.org/10.3906/sag-2003-138DOI Listing
November 2020

Prevention of DMBA-induced mammary gland tumors in mice by a dual-function inhibitor of JAK3 and EGF receptor tyrosine kinases.

Expert Opin Ther Targets 2020 04 2;24(4):379-387. Epub 2020 Mar 2.

Division of Hematology-Oncology, Department of Pediatrics and Developmental Therapeutics Program, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA.

: We tested the chemopreventive effect of WHI-P131 in side by side evaluation with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer model.: One hundred BALB/cmice were divided into five groups. (i) Control (ii) DMBA (iii)  DMBA+ Paclitaxel (10 mg/kg) (iv)  DMBA+WHI-P131 (Janex1, 50 mg/kg of BW, i.p, three times per week) ("J") (v) DMBA+P+J. The duration of study was 25 weeks.: Our findings demonstrate that WHI-P131 impedes DMBA-induced carcinogenesis, reduces size, weight, and load of tumors ( < 0.001) in DMBA-challenged mice and improves their survival outcome ( < 0.01). The tumors developing despite WHI-P131 chemoprevention displayedattenuated levels of JAK3, STAT3, and NF-κB as well as increased I-κB expression ( < 0.001). Notably, these tumors exhibited significantly decreased levels of phosphorylated AKT-PI3-Kinase pathway signaling proteins p-mTOR, p-p70S6K1, and p-4E-BP1 ( < 0.001). Our findings are consistent with a model in which DMBA-induced malignant clones with low-level expression of the six signature proteins JAK3/STAT3/NF-κB/p-mTOR, p-p70S6K1/p-4E-BP1, albeit not as aggressive as their JAK3/STAT3/NF-κB overexpressing counterparts are capable of escaping chemo-preventive effects of WHI-P131.: These insights may provide the foundation for new chemo-preventive strategies in which WHI-P131 is applied to prevent the development of aggressive forms of breast cancer.
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http://dx.doi.org/10.1080/14728222.2020.1737014DOI Listing
April 2020

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice.

Biomedicines 2020 Feb 3;8(2). Epub 2020 Feb 3.

Department of Physiology, School of Medicine, Istanbul Medipol University, Istanbul 34810, Turkey.

Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways.
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http://dx.doi.org/10.3390/biomedicines8020023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168297PMC
February 2020