Publications by authors named "Tolga Mercantepe"

49 Publications

The protective effects of topiramate on intestinal injury induced with infrarenal aortic occlusion via oxidative stress and apoptosis.

Clin Exp Hypertens 2021 May 10:1-6. Epub 2021 May 10.

Department of General Surgery, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

: Prolonged surgical procedures and some clinical conditions such as surgeries of thoracoabdominal aorta, mesenteric ischemia, cardiopulmonary bypass, strangulated hernias and neonatal necrotizing enterocolitis may cause decreased perfusion and injury of relevant organs and tissues. After reperfusion, injuries may get worse, leading to ischemia-reperfusion (I/R) injury. Reperfusion following arterial clamping allows oxygen to ischemic tissues and produce injury by multiple mechanisms, including neutrophilic infiltration, intracellular adhesion molecules, and generation of reactive oxygen radicals. In this study with the analysis of SOD, MDA and Caspase-3 levels, we aimed to investigate the effect of topiramate on the outcome of I/R occured after abdominal aorta clamping on rats.: Totaly 24 Sprague-Dawley male rats were randomly divided into three experimental groups; the control group ( = 8), I/R ( = 8) and I/R+ topiramate ( = 8). Topiramate (100 mg/kg/day); 50 mg/kg (single dose) was administered intraperitoneally after being diluted with saline 5 days before I/R.: The intestinal tissue of the ischemia group displayed hemorrhage, Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields as a result of aortic occlusion. We also observed that MDA levels and Caspase-3 positivity increased and SOD levels decreased in the small intestine. However, topiramate administration decreased Crypts of Lieberkuhn degeneration, ulceration, vascular congestion and edematous fields, Caspase-3 positivity, and MDA levels.: Our findings suggest that topiramate is effective against aortic occlusion-induced intestinal injury by reducing oxidative stress and apoptosis.
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http://dx.doi.org/10.1080/10641963.2021.1925680DOI Listing
May 2021

Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction.

Behav Brain Res 2021 Jun 15;408:113290. Epub 2021 Apr 15.

Recep Tayyip Erdogan University, Faculty of Medicine, Department of Biochemistry, Rize, Turkey. Electronic address:

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. The aim of this study was to investigate the role of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway and the potential inhibitory effects of apelin-13 in the mechanism of cisplatin-induced hippocampal damage and cognitive impairment. Apelin-13 was administered to adult sprague dawley male rats at a dose of 20 nmol/kg every day for 4 weeks, cisplatin was administered at a dose of 5 mg/kg once a week for 4 weeks. The spatial and recognition memory tests of the rats were performed on the 5th week. BDNF and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were measured by ELISA in hippocampal homogenates. Pyramidal neuron and glial cell damage in the hippocampal CA1, CA3 and dentate gyrus (DG) were analyzed histologically. TrkB activity in the hippocampus was determined by immunohistochemical methods. Cisplatin impaired spatial and recognition memory in rats, while apelin-13 improved spatial memory but did not affect recognition memory. Cisplatin suppressed BDNF in the hippocampus while increased IL-1β and TNF-α. In contrast, apelin-13 administration increased BDNF but significantly suppressed TNF-α and IL-1B. Cisplatin caused pyramidal neuron and glial cell damage in CA1, CA3 and DG. In the cisplatin + apelin-13 group, however, pyramidal neuron and glial cell damage was less than those without apelin-13. Cisplatin increased TrkB activity in the hippocampus, which was counteracted by apelin-13. In conclusion, apelin-13 reduced the cisplatin-induced cognitive deficiency, by suppressing inflammation and stimulating the synthesis and activation of neurotrophic factors in hippocampal tissue.
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http://dx.doi.org/10.1016/j.bbr.2021.113290DOI Listing
June 2021

The protective effect of astaxanthin on cisplatin-induced ototoxicity.

Adv Clin Exp Med 2021 Mar;30(3):315-321

Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Background: Promising studies have been conducted with many substances to reduce the ototoxic effects of cisplatin, but there is no treatment that completely eliminates the ototoxic effect.

Objectives: To determine the effectiveness of astaxanthin (ASX) as a protective agent against cisplatin-induced ototoxicity.

Material And Methods: Thirty-six rats were randomly divided into 6 groups. Group 1 received no drug injections except for anesthetics; group 2 received intraperitoneal (IP) olive oil only for 8 days; group 3 received only IP ASX 75 mg/kg dissolved in olive oil for 8 days; group 4 received a single dose of only IP 16 mg/kg cisplatin on the 5th day; group 5 received 25 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day; group 6 received 75 mg/kg ASX IP daily for 8 days and a single 16 mg/kg dose of cisplatin on the 5th day. The animals were tested for distortion product otoacoustic emissions (DPOAE) before and 3 days after cisplatin treatment. The animals in all groups were sacrificed under anesthesia on the 10th day. Before sacrifice, inferior vena cava blood samples were drawn into commercial tubes for biochemical analysis and their cochlea were prepared for histological analysis.

Results: The ASX+cisplatin groups demonstrated significantly higher DPOAE thresholds when compared to the cisplatin-only group (p < 0.05). The ASX 25 mg/kg/day+cisplatin group showed a significant increase in total antioxidant capacity compared to the cisplatin-only group, whereas the ASX 75 mg/kg/day+cisplatin group had significantly lower total oxidative stress and oxidative stress index. Histologic results showed that the cortical organ was better preserved in the ASX+cisplatin groups compared to the cisplatin-only group, and the degeneration in the spiral ganglion and inner and outer hair cells was less visible in the ASX groups.

Conclusions: Astaxanthin can protect hearing from cisplatin-induced ototoxicity, prevent cellular degeneration and significantly reduce oxidative stress.
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http://dx.doi.org/10.17219/acem/133081DOI Listing
March 2021

Effects of long-term Doppler ultrasound exposure on cochlea and cochlear nucleus in prenatal period in an experimental model.

J Matern Fetal Neonatal Med 2021 Feb 21:1-8. Epub 2021 Feb 21.

Department of Otorhinolaryngology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Background: New generation Doppler ultrasonography (DUSG) application effects on cochlea and cochlear nucleus (CN) are unclear. We aimed to investigate the effects of new generation DUSG application at different frequencies in prenatal period on cochlea and CN in rats.

Objective: Twenty-four pregnant female rats were divided into three groups ( = 8). Group 1 was the control group and was not subjected to any treatment. Group 2 was determined as the USG every day (USGED) treatment group. Group 2 has received DUSG application every day from the 4th to 18th day (20 min/15 per day). Group 3 has received DUSG application as "2 days/one dose as every other day application" (USG2D1) from the 4th to 18th day (20 min/8 every other day). Twenty-four female rats were sacrificed in 21 days. Also, 24 pups were sacrificed after two days. First day after born, the cochlear activities of the right ears of all pups were examined using DPOAEs. Second day, neural tissues from CN were evaluated histopathologically and immunohistochemically.

Results: There was no any statistical difference between the groups in respect of histopathologically. USGED group showed mild caspase-3 positive neurons and glial cells. However, there was no significant difference between the USGED and other groups (>.05). Similarly, the rats applied with USG2D1 had mild caspase-3 expression, but no significant difference between the USG2D1 and other groups (>.05). Differences in DPOAE amplitudes, and therefore in cochlear activity, between the groups were revealed. The decrease in cochlear activity between the groups involved frequencies at 2, 8, 16, and 32 kHz (<.05).

Conclusions: Multiple administration of new generation DUSG to pregnant rats has not shown harmful effects on the cochlear neural tissue. High frequencies are more sensitive in cochlea to apply DUSG.
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http://dx.doi.org/10.1080/14767058.2021.1875431DOI Listing
February 2021

Melatonin improves periodontitis-induced kidney damages by decreasing inflammatory stress and apoptosis in rats.

J Periodontol 2020 Nov 30. Epub 2020 Nov 30.

3D Medical and Industrial Design Laboratory, Istanbul University, Istanbul, Turkey.

Background: Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1β, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine.

Results: Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1β), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05).

Conclusion: Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.
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http://dx.doi.org/10.1002/JPER.20-0434DOI Listing
November 2020

Protective effects of nebivolol on ovarian ischemia-reperfusion injury in rat.

J Obstet Gynaecol Res 2020 Nov 22;46(11):2407-2416. Epub 2020 Sep 22.

Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Aim: Ovarian torsion is a common gynecological emergency of reproductive ages, occurring at rates of 2.7-7.4%. This study aimed to evaluate the antioxidant effects of Nebivolol (NEB) and histopathological changes in experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries.

Methods: Forty-eight adult female rats were randomly separated into six groups as group 1 (control) receiving an oral saline solution for 3 days; group 2 (I) that underwent ischemia for 3 h with the application of atraumatic vascular clips; group 3 (I/R); group 4 (I + NEB) receiving 10 mg/kg NEB by oral gavage 30 min prior to the ischemia induction; group 5 (I/R + NEB) receiving 10 mg/kg NEB, and group 6 (control + NEB) receiving oral 10 mg/kg NEB for 3 days before ischemia induction followed by consequent reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured biochemically.

Results: The levels of MDA and tumor necrosis factor-alpha (TNF-α), and TUNEL assay positivity scores increased in the I and I/R groups. GSH levels decreased in all case groups (P < 0.05). The oral administration of NEB (10 mg/kg) to the I- and I/R-groups reduced the levels of MDA and TNF-α and TUNEL assay immunopositivity scores (P < 0.05). GSH levels increased in the treatment groups.

Conclusion: The current experimental ovarian torsion study suggests a protective role for NEB against I and I/R injury in rat ovaries. NEB may be a novel agent for decreasing ovarian I/R injury.
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http://dx.doi.org/10.1111/jog.14503DOI Listing
November 2020

Tea Grape Reduces Abdominal Aortic Occlusion-Induced Lung Injury.

Braz J Cardiovasc Surg 2020 08 1;35(4):512-520. Epub 2020 Aug 1.

Kerimali Akyilzdiz.

Introduction: Ischemia-associated mortality caused by aortic cross-clamps, as in ruptured abdominal aorta aneurysm surgeries, and reperfusion following their removal represent some of the main emergency conditions in cardiovascular surgery. The purpose of our study was to examine the potential protective effect of tea grape against aortic occlusion-induced lung injury using biochemical, histopathological, immunohistochemical, and quantitative analyses.

Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups: control (healthy), glycerol + ischemia/reperfusion (I/R) (sham), I/R, and I/R + tea grape.

Results: Following aortic occlusion, we observed apoptotic pneumocytes, thickening in the alveolar wall, edematous areas in interstitial regions, and vascular congestion. We also observed an increase in pulmonary malondialdehyde (MDA) levels and decrease in pulmonary glutathione (GSH). However, tea grape reduced apoptotic pneumocytes, edema, vascular congestion, and MDA levels, while increased GSH levels in lung tissue.

Conclusion: Our findings suggest that tea grape is effective against aortic occlusion-induced lung injury by reducing oxidative stress and apoptosis.
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http://dx.doi.org/10.21470/1678-9741-2019-0392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454615PMC
August 2020

The Role of Vaccinium Myrtillus in the Prevention of Renal Injury in an Experimental Model of Ruptured Abdominal Aortic Aneurysm.

Braz J Cardiovasc Surg 2020 08 1;35(4):490-497. Epub 2020 Aug 1.

Department of Medical Biochemistry, Recep Tayyip Erdogan University, Faculty of Medicine, Rize, Turkey.

Objective: To examine the biochemical and histopathological renal effects of ischemia/reperfusion (I/R) injury using a ruptured abdominal aortic aneurysm (RAAA) model in rats and to investigate the potential protective effects of whortleberry (Vaccinium myrtillus).

Methods: Thirty-two male Sprague-Dawley rats were randomly assigned into four groups - control, sham (I/R+glycerol), I/R, and I/R+whortleberry. Midline laparotomy alone was performed in the control group. Atraumatic abdominal clamps were attached under anesthesia to the abdominal aorta beneath the level of the renal artery in the groups subjected to I/R. Sixty-minute reperfusion was established one hour after ischemia. The sham group received five intraperitoneal doses of glycerol five days before I/R. The I/R+whortleberry group received a single intraperitoneal 50 mg/kg dose diluted with saline solution five days before I/R. All animals were finally euthanized by cervical dislocation following 60-min reperfusion.

Results: Increases were observed in malondialdehyde (MDA) levels and tubular necrosis scores (TNS) in thin kidney tissues and in numbers of apoptotic renal tubule cells, together with a decrease in glutathione (GSH) levels, in sham and I/R groups. In contrast, we observed a decrease in MDA levels, TNS, and numbers of apoptotic renal tubule cells, and an increase in GSH levels with whortleberry treatment compared to the I/R group.

Conclusion: Our findings suggest that whortleberry may be effective against acute kidney injury by reducing oxidative stress and apoptosis.
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http://dx.doi.org/10.21470/1678-9741-2019-0121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454617PMC
August 2020

The Protective Effects of Perindopril Against Acute Kidney Damage Caused by Septic Shock.

Inflammation 2021 Feb;44(1):148-159

Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, 53100, Rize, Turkey.

Acute kidney injury (AKI) resulting from septic shock caused by sepsis is an important health problem encountered at rates of 55-73%. Increasing oxidative stress and inflammation following sepsis is a widely observed condition with rising mortality rates. The purpose of this study was to determine whether perindopril (PER) can prevent sepsis-associated AKI with its antioxidant, anti-inflammatory, and anti-apoptotic effects. The control group received an oral saline solution only for 4 days. Cecal ligation and puncture (CLP)-induced sepsis only was applied to the CLP group, while the CLP + PER (2 mg/kg) received CLP-induced sepsis together with 2 mg/kg PER via the oral route for 4 days before induction of sepsis. Finally, all rats were euthanized by anesthesia and sacrificed. TBARS, total SH levels and NF-κβ, TNF-α, and Caspase-3 expression were then calculated for statistical analysis. TBARS, total SH, NF-kβ/p65, TNF-a, and Caspase-3 levels increased in the CLP group. In contrast, oral administration of PER (2 mg/kg) to septic rats reduced TBARS levels and NF-kβ/p65, TNF-α, and Caspase-3 immunopositivity at biochemical analysis. PER treatment appears to be a promising method for preventing sepsis-induced acute kidney injury through its antioxidant anti-inflammation and anti-apoptotic activities.
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http://dx.doi.org/10.1007/s10753-020-01316-8DOI Listing
February 2021

White Tea Reduced Bone Loss by Suppressing the TRAP/CTX Pathway in Ovariectomy-Induced Osteoporosis Model Rats.

Cells Tissues Organs 2020 19;209(1):64-74. Epub 2020 Jun 19.

Department of Radiology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Osteoporosis is an important skeletal disease characterized by bone weakness and high risk of fracture in postmenopausal women. Tea consumption is known to play an important role in the prevention or alleviation of osteoporosis. However, the therapeutic effects of aqueous extracts of white tea (WT) have not been evaluated in osteoporosis rat models. The aim of this study was to investigate the potential anti-osteoporotic role of WT in ovariectomized (OVX) rats. WT was given orally at 0.5% w/v doses for 12 weeks in OVX rats. Biochemical parameters in blood samples, bone tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type 1 collagen (CTX) and estradiol levels were evaluated. Bone mineral density and bone mineral content values were measured in the left femur. In addition to histopathological examination, osteolcalcin, osteopontin and TUNEL levels were determined. OVX group data demonstrated that bone loss occurred by thinning of the metaphyseal growth plates of the femur. Similarly, the levels of TRAP and CTX, markers of osteoclastic activity, were found to be high concurrently with a decrease in femoral bone mineral density. In addition, increased osteolcalcin and osteopontin levels were present in the metaphyseal growth zones. On the other hand, while TRAP and CTX levels were suppressed in the OVX-WT group, bone mineral content increased. In ad-dition, TUNEL, osteocalcin and osteopontin positivity decreased in the right femoral metaphysis growth zones, proliferating zone and resting zone cells. These results showed that chronic WT consumption has a protective effect by reducing bone resorption in OVX-induced osteoporotic rats.
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http://dx.doi.org/10.1159/000507791DOI Listing
March 2021

The protective effects of adalimumab on intestinal injury induced with infrarenal aortic occlusion.

Ulus Travma Acil Cerrahi Derg 2020 May;26(3):366-372

Department of Biochemistry, Faculty of Medicine, Recep Tayyip Erdoğan University Faculty of Medicine, Rize-Turkey.

Background: The present study aims to observe the effects of ischemia-reperfusion (IR) on small intestines at a molecular level and to prospectively assess the potential preventive role of adalimumab (ADA) and antioxidants.

Methods: A total of 24 male Sprague-Dawley rats were randomly divided into three groups-a control group, an IR group and an IR+ADA group.

Results: Although there was no change in SOD levels in the small bowel tissue of the IR group, we observed increased malondialdehyde (MDA) levels and increased numerical density of caspase-3 and TNF-α positive enterocytes p=0.00 and p=0.00, respectively). We also observed that IR caused the degeneration of villus crypt structures.

Conclusion: We found that ADA treatment reduced MDA levels and decreased the numerical density of caspase-3 and TNF-α positive enterocytes compared to the IR group (p=0.00; p=0.011; p=0.00, respectively). We conclude that ADA can be beneficial in preventing intestinal injury that arises from IR.
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http://dx.doi.org/10.14744/tjtes.2019.59607DOI Listing
May 2020

Melatonin ameliorates periodontitis-related inflammatory stress at cardiac left ventricular tissues in rats.

J Periodontol 2020 11 19;91(11):1486-1494. Epub 2020 May 19.

School of Medicine, Department of Biochemistry, Recep Tayyip Erdogan University, Rize, Turkey.

Background: The aim of this experimental rat study was to investigate the potential inflammatory effects of periodontitis on cardiac left ventricular tissue and the therapeutic activity of melatonin on these effects.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Experimental periodontitis was induced by placing and maintaining 3.0 silk ligatures at a peri marginal position on the left and right mandibular first molars for 5 weeks. Afterward, following the removal of ligatures, melatonin (10 mg/body weight) to Ep-Mel group, and vehicle (saline) to Ep and control groups were administered intraperitoneally for 14 days. On the first day of the eighth week, mandibular and cardiac left ventricular tissue samples were obtained following the euthanasia of the rats in all groups. Alveolar bone loss measurements were made on histological and microcomputed tomographic slices. Cardiac tissue levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), matrix metalloproteinase-9 (MMP-9), and cardiac Troponin-T (cTnT) were evaluated by appropriate biochemical methods.

Results: Measurements made on the histological and microcomputed tomographic slices showed that melatonin significantly limits the ligature-induced periodontal tissue destruction (P <0.01). In addition, melatonin was detected to cause a significant decrease of MDA, MMP-9, and cTnT levels which were found to be significantly higher on rats with Ep (P <0.05) while having no significant effect on antioxidant levels (GSH, SOD, and CAT) (P >0.05).

Conclusion: Melatonin might be regarded as an important supportive therapeutic agent to reduce the early degenerative changes and possible hypertrophic remodeling at cardiac left ventricular tissues provoked by periodontitis-related bacteria and/or periodontal inflammation.
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http://dx.doi.org/10.1002/JPER.19-0685DOI Listing
November 2020

The effects of whortleberry on ischemia reperfusion-induced myocardial injury in rats.

Turk Gogus Kalp Damar Cerrahisi Derg 2020 Jan 23;28(1):63-69. Epub 2020 Jan 23.

Department of Medical Biochemistry, Recep Tayyip Erdoğan University Medical Faculty, Rize, Turkey.

Background: The aim of this study was to investigate the potential protective effect of whortleberry by examining the effects on heart tissue at the molecular level of ischemia-reperfusion injury caused by surgical repair of a ruptured abdominal aortic aneurysm.

Methods: Between May 2018 and February 2019, a total of 32 male Sprague-Dawley rats were randomly assigned into control, sham (ischemia-reperfusion+glycerol), ischemia-reperfusion, and ischemia-reperfusion+whortleberry groups. Hypovolemic shock was applied to the rats in the ischemia-reperfusion groups for one hour. The abdominal aorta was explored following midline laparotomy and atraumatic microvascular clamps were applied from the infrarenal level. Following one-hour ischemia, the clamps were removed, and reperfusion was established for two hours. In the sham group, intraperitoneal glycerol once daily was applied five days before surgery. In the whortleberry group, whortleberry treatment was administered via the intraperitoneal route five days before ischemia-reperfusion.

Results: The ischemia-reperfusion group exhibited a decrease in the glutathione levels and an increase in the malondialdehyde levels (p<0.01 and p<0.01, respectively). We also observed an increase in the caspase-3 positivity in cardiac myofibrils (p<0.01). Whortleberry administration lowered both malondialdehyde levels and numerical density of caspase-3 positive cardiac myofibrils, while increasing the heart tissue glutathione levels, compared to the ischemia-reperfusion alone group (p<0.01, p=0.011, and p=0.011, respectively).

Conclusion: Whortleberry may be beneficial in preventing cardiac tissue damage caused by ischemia-reperfusion in the surgical repair of ruptured abdominal aortic aneurysms.
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http://dx.doi.org/10.5606/tgkdc.dergisi.2020.18389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067026PMC
January 2020

Prenatal Effects of a 1,800-MHz Electromagnetic Field on Rat Livers.

Cells Tissues Organs 2019 4;207(3-4):187-196. Epub 2019 Dec 4.

Department of Medical Services and Techniques, Health Care Services Vocational School, Recep Tayyip Erdogan University, Rize, Turkey.

The use of devices, including mobile phones, generating electromagnetic fields (EMF) is widespread and is progressively increasing. It has also been shown that EMF may have detrimental effects. This is the first study to investigate the postnatal biochemical and histological effects of prenatal exposure of rat livers to 1,800-MHz EMF at different time intervals in uteroplacental life. The 3 EMF groups of rats were exposed to 1,800-MHz EMF for 6, 12, or 24 h daily for 20 days. Unexposed rats served as control group. All rats were subjected to anesthesia, and on postnatal day 60, the livers were excised, and blood was collected for histological and biochemical analyses. Malondialdehyde levels were significantly higher in the exposed groups than the unexposed controls (p < 0.05). In contrast, EMF-exposed groups had lower liver tissue glutathione levels than controls (p < 0.05). Serum Ca2+, alanine transaminase, and aspartate aminotransferase levels were higher in EMF-exposed groups than controls (p < 0.05). In addition, liver tissue total oxidant status levels were increased (p < 0.05), and liver tissue total antioxidant status levels were decreased (p < 0.05) compared to the control group. Furthermore, in the EMF groups, extensive vacuolation and degeneration of the hepatocytes in the portal area, as well as those surrounding the sinusoids, were evident. Affected hepatocytes had polygonally shaped nuclei and vacuolic cytoplasm imparting eosinophilic staining. Loss of cellular membrane integrity and invaginations, as well as picnotic nuclei, was prominent. This study has shown that intrauterine liver damage caused by 1,800-MHz EMF exposure persists into puberty in rats.
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http://dx.doi.org/10.1159/000504506DOI Listing
July 2020

The protective effects of angiotensin-converting enzyme inhibitor against cecal ligation and puncture-induced sepsis via oxidative stress and inflammation.

Life Sci 2020 Jan 13;241:117051. Epub 2019 Nov 13.

Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, 53100, Rize, Turkey.

Aims: Sepsis is a severe public health problem affecting millions of individuals, with global mortality rates caused by lower respiratory tract infections are approximately 2.38 million people a year die from respiratory failure caused by infection. Although ACE is known to contribute to damage in septicemia, the pathophysiological mechanisms of sepsis remain unclear. While mortality can be significantly reduced through effective and sensitive antibiotic therapy, antibiotic resistance restricts the use of these drugs, and the investigation of novel agents and targets is therefore essential. Our aim was to determine whether Perindopril (PER) has anti-inflammatory and antioxidant capable of preventing these adverse conditions resulting in injury in previous studies.

Main Methods: Sprague Dawley rats were randomly assigned into the control group, received oral saline solution alone for four days. the cecal ligation and puncture (CLP) group, underwent only cecal ligation and puncture induced sepsis, while the CLP + PER (2 mg/kg) underwent cecal ligation and puncture-induced sepsis together with oral administration of 2 mg/kg PER for four days before induction of sepsis.

Key Findings: Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), Caspase-3 and nuclear factor kappa B (NF-kβ/p65) levels increased in the CLP group. On the other hand, PER (2 mg/kg) oral administration to septic rats decreased MDA, TNF-α and increase glutathione (GSH) in the lung tissue. In addition, PER administration also decreased the lung tissue NF-κB and Caspase-3 immunopositivity against sepsis.

Significance: PER treatment may represent a promising means of preventing sepsis-induced lung injury via antioxidant and anti-inflammation effects.
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http://dx.doi.org/10.1016/j.lfs.2019.117051DOI Listing
January 2020

An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats.

Eur J Pharmacol 2019 Dec 12;865:172790. Epub 2019 Nov 12.

Recep Tayyip Erdogan University, Faculty of Medicine, Department of Histology and Embryology, 53100, Rize, Turkey.

Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I)+250 group, and Group 5, the ischemia (I)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R)+250 group, and Group 7, the ischemia/reperfusion (I/R)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-α) levels in ovarian tissue increased following I/R, while estradiol (E) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-κβ) expression levels also increased. MDA and TNF-α concentrations decreased in the MET treatment groups, while GSH and E levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-κβ.
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http://dx.doi.org/10.1016/j.ejphar.2019.172790DOI Listing
December 2019

Evaluation of the protective effects of amifostine and melatonin against cisplatin induced testis injury via oxidative stress and apoptosis in rats.

Exp Mol Pathol 2020 02 5;112:104324. Epub 2019 Nov 5.

Recep Tayyip Erdogan University, School of Medicine, Biochemistry Department, Rize, Turkey. Electronic address:

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http://dx.doi.org/10.1016/j.yexmp.2019.104324DOI Listing
February 2020

Pelvic Radiation-Induced Testicular Damage: An Experimental Study at 1 Gray.

Syst Biol Reprod Med 2020 Apr 26;66(2):89-98. Epub 2019 Oct 26.

Department of Histology and Embryology, Recep Tayyip Erdogan University Faculty of Medicine, Rize, Turkey.

Therapeutic radiation of the pelvic region has been shown to cause damage to testicular germ cells. In this study we aimed to evaluate the effects of a low therapeutic dose of 1 Gy on the induction of cellular and histological damage in early-stage testicular germ cells and the impact of this radiation on offspring sex ratio. Unirradiated and irradiated male rats were mated with unirradiated female rats. Female rats were followed and the sex of the offspring was determined. The male rats were sacrificed at the end of the second week, and the testicular germ cells were subjected to genetic analysis along with cytological and histopathological examination. Sperm DNA was amplified with primers specific to testis-specific Y-linked protein, rat actin beta and testis-specific X-linked genes. The resulting products were separated by capillary electrophoresis. Histopathological changes were investigated by light microscopy along with the TUNEL assay and immunohistochemical staining for caspase-3. There was no significant difference between the two groups for sex ratio and size of offspring. The number of sperm cells bearing X or Y chromosomes' did not differ significantly between these two groups. However, a 1 Gy dose of radiation caused significant cytopathological and histopathological changes in the testicular tissue. In the irradiated group, edematous regions were evident. The number of caspase-3 positive cells in the germinal epithelium of the seminiferous tubules was also significantly higher in the irradiated group. Our results showed that low-dose radiation induced apoptosis and caused significant cyto- and histopathological changes in the testicular tissue. Further research is required to fully elucidate their contribution to apoptosis and if low-dose radiation may potentially lead to long-term effects in the offspring. These results may also lead us to develop a new technique using the caspase-3 staining to monitor the susceptibility to low dose radiation.
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http://dx.doi.org/10.1080/19396368.2019.1679909DOI Listing
April 2020

Less Use of the Bipolar Cautery can Prevent Postlaminectomy Epidural Fibrosis: An Experimental Study in Rats.

Turk Neurosurg 2020 ;30(2):217-224

University of Health Sciences, Samsun Health Practices and Research Center, Department of Neurosurgery, Samsun, Turkey.

Aim: To investigate the role of bipolar electrocautery in the occurrence of epidural fibrosis following lumbar spine laminectomy in a rat model.

Material And Methods: Fourteen male Sprague-Dawley rats (age: 4-6 months, weight: 250-300 g) were randomly divided into two groups, a bipolar group (Group I) and a control group (Group II). Laminectomy was performed between the L1 and L3 levels. In Group I (n=7), a laminectomy was carried out and soft tissue around the spinal cord was coagulated by using a bipolar electrocautery. In the control group (n=7), only laminectomy was performed. The animals were sacrificed 4 weeks after surgery, and post-laminectomy epidural fibrosis (PLEF) was evaluated. Macropathological, qualitative and quantitative histological evaluations as well as immunohistochemical staining including transforming growth factor-β (TGF-β), collagen I and collagen III were performed.

Results: The numbers of TGF-β positive cells staining (PCS) were 3.00 ± 0.46 for Group I and 1.00 ± 0.52 for Group II. The numbers of collagen I PCS were 2.00 ± 0.93 for Group I and 1.25 ± 0.46 for Group II. The numbers of collagen III PCS were 2.25 ± 0.76 for Group I, 1.25 ± 0.46 for Group II, and TGF-β PCS than Group II (p≤0.05). Compared with the control group, Group I's formation of epidural fibrosis was significantly increased.

Conclusion: Our study clearly demonstrated that the use of bipolar cauterisation is associated with increased PLEF in the experimental animal model. Thus, limiting the use of bipolar cauterisation may be effective in reducing this complication.
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http://dx.doi.org/10.5137/1019-5149.JTN.27544-19.2DOI Listing
July 2020

The radioprotective effect of N-acetylcysteine against x-radiation-induced renal injury in rats.

Environ Sci Pollut Res Int 2019 Oct 7;26(28):29085-29094. Epub 2019 Aug 7.

Department of Internal Medicine, Faculty of Medicine, Recep Tayyip Erdogan University, 53100, Rize, Turkey.

The purpose of this study was therefore to investigate the effects of radiotherapy on the kidney and the potential use of agents such as N-acetylcysteine (NAC) in developing a future therapeutic protocol for radiation-induced nephrotoxicity at the histopathological and biochemical levels. Our study consisted of three groups: control (oral saline solution only; group 1), irradiation (IR; group 2), and NAC + IR (group 3). The irradiation groups received a single dose of whole-body 6-Gy x-irradiation. The NAC group received 300 mg/kg by the oral route for 7 days, from 5 days before irradiation to 2 days after. All subjects were sacrificed under anesthesia 2 days after irradiation. IR increased tubular necrosis scores (TNS), MDA, and caspase-3 expression, while reducing renal tissue GSH levels. We also observed dilation in renal corpuscles and tubules. Capillary congestion was present in the intertubular spaces. NAC reduced the levels of TNS, MDA, and caspase-3 expression, but increased the levels of renal tissue GSH. ROS-scavenging antioxidants may represent a promising means of preventing renal injury in patients undergoing radiotherapy.
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http://dx.doi.org/10.1007/s11356-019-06110-0DOI Listing
October 2019

Radioprotective effect of endogenous melatonin secretion associated with the circadian rhythm in irradiated rats.

Int J Radiat Biol 2019 09 29;95(9):1236-1241. Epub 2019 Jul 29.

Department of Histology and Embryology, Recep Tayyip Erdogan University , Rize , Turkey.

We investigated the radioprotective effect of endogenous melatonin release at different times associated with the circadian rhythm on head and neck radiotherapy. Two groups of animals were subjected daily to 8 Gy single fraction radiotherapy in the head and neck region from 5:00 to 6:00 (the morning group) or from 19:00 to 20:00 (the evening group). Corresponding untreated groups served as controls. Submandibular glands from rats sacrificed on the seventh day after irradiation were assessed biochemically and histopathologically. Melatonin, malondialdehyde and superoxide dismutase levels in blood collected immediately prior to irradiation were measured with rat-specific ELISA kits. In irradiated rats, melatonin, malondialdehyde and superoxide dismutase levels were significantly higher in the evening group than in the morning group. In nonirradiated rats, melatonin and superoxide dismutase levels were significantly higher in the evening group than in the morning group. The areas of seromucous acinar cells were similar between the irradiated and nonirradiated evening groups, but the area was higher in the evening irradiated group than in the morning irradiated group. Consideration of endogenous melatonin secretion associated with the circadian rhythm may offer new therapeutic solutions for the complications of head and neck radiotherapy.
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http://dx.doi.org/10.1080/09553002.2019.1642532DOI Listing
September 2019

Effects of Infliximab against Methotrexate Toxicity in Splenic Tissue via the Regulation of CD3, CD68, and C200R in Rats.

Cells Tissues Organs 2018 8;206(6):308-316. Epub 2019 Jul 8.

Department of Internal Medicine, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Methotrexate (MTX), which has been used in clinical practice for approximately 70 years, is still widely employed in the treatment of rheumatoid arthritis (RA), psoriasis, and cancer. Although MTX toxicity causes nephrotoxicity, hepatotoxicity, bone marrow suppression, pulmonary fibrosis, and gastrointestinal damage, previous studies have not addressed splenic toxicity. This is the first study to examine the effectiveness of infliximab (INF) against MTX-induced toxicity in splenic tissues via the regulation of CD3, CD68, and C200R. We investigated the effects of MTX on macrophages and T lymphocytes in the spleen at the molecular level and examined the protective potential of the tumor necrosis factor (TNF)-α antagonist INF against MTX toxicity. Three groups of rats were set up. Group 1 received saline solution only, group 2 a single dose of MTX (20 mg/kg), and group 3 INF (7 mg/kg) before administration of a single dose of MTX (20 mg/kg). All injections were given intraperitoneally. Spleen tissues were removed 5 days after MTX administration and evaluated for CD3, CD68, and CD200R using immunohistochemical staining. Finally, the mean numerical density of CD3+, CD68+, and CD200R+ cells was estimated by a histopathologist using StereoInvestigator 8. MTX increased the numerical densities of CD3+, CD68+, and CD200R+ cells (p < 0.05). We also observed that INF reduced the numerical densities of these cells following MTX administration (p < 0.05). INF may, therefore, be a promising candidate for the prevention of the deleterious effects on spleen tissue of MTX, used in the treatment of RA and cancer.
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http://dx.doi.org/10.1159/000500905DOI Listing
July 2019

Protective Effect of Whortleberry Extract on Salivary Gland Damage Induced by Neck Irradiation in Rats.

Ear Nose Throat J 2019 Jul 28;98(6):E64-E69. Epub 2019 Apr 28.

2 Medical Faculty, Department of Otorhinolaryngology, Recep Tayyip Erdogan University, Rize, Turkey.

Radiotherapy is a method of treatment used on malignant head and neck tumors; however, it may lead to adverse effects by influencing other tissues because its effects are not specific to tumor tissues. These adverse effects limit the effectiveness of the treatment and sometimes lead to termination of the treatment. This study aims to histopathologically and biochemically investigate the protective effect of whortleberry against the cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy. The rats were divided into 6 groups. One group was given radiotherapy only, one group was given radiotherapy and 100 mg/kg of whortleberry, and one group was given radiotherapy and 200 mg/kg of whortleberry. The remaining 3 groups were designated as whortleberry, sham, and control groups. At the end of the study, samples collected were histopathologically and biochemically analyzed. In the group given radiotherapy only, acinar areas were reduced histopathologically, whereas ductal areas increased ( < .01). Oxidative stress increased only in the group given radiotherapy, whereas the oxidative stress levels in the other groups were close to those in the control groups. In conclusion, whortleberry reduces cellular degeneration and oxidative stress that take place in salivary glands due to radiotherapy.
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http://dx.doi.org/10.1177/0145561319846868DOI Listing
July 2019

Correction to: Protective effects of amifostine, curcumin and melatonin against cisplatin-induced acute kidney injury.

Naunyn Schmiedebergs Arch Pharmacol 2019 Apr;392(4):511

Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53010, Rize, Turkey.

Due to an oversight, Drug treatment (Material and Methods section) in Mercantepe et al. (2018) Naunyn Schmiedebergs Arch Pharmacol. 2018 Sep;391(9):915-931. doi: https://doi.org/10.1007/s00210-018-1514-4 .
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http://dx.doi.org/10.1007/s00210-019-01633-2DOI Listing
April 2019

The effect of white tea on serum TNF-α/NF-κB and immunohistochemical parameters in cisplatin-related renal dysfunction in female rats.

Biomed Pharmacother 2019 Apr 22;112:108604. Epub 2019 Feb 22.

Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey.

Objective: Nephrotoxicity is the most important side effect of the antineoplastic drug cisplatin, thereby restricting its use. The aim of this study was to investigate the protective effects of white tea infusions (WT) against renal damage induced by cisplatin (CP) in rats by biochemical and histopathological means.

Materials And Methods: This study used 24 female Sprague Dawley rats at 12-14 weeks of age and weighing 250-300 g. Rats were divided into three groups: Control, CP and CP + WT groups. CP was injected 7 mg/kg i.p as a single dose/rat in the CP group. White tea was given at a dose of 0.5% (w/v) for 4 weeks. At the end of the experiment, blood urea nitrogen (BUN), creatinine, uric acid, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nuclear factor kappa B (NF-κB) along with caspase-3 in the kidney were evaluated in study.

Results: BUN, creatinine, TNF-α, NF-κB and IL-6 levels of the CP group showed a statisically significant increase in comparison to the control group. TNF-α, NF-κB and IL-6 levels showed a statistically significant decrease in the CP + WT group with respect to the CP group. Caspase-3 levels in tubular epithelial cells decreased in CP + WT group compared with CP group (p = 0.02).

Conclusion: White tea infusions reduced significantly the nephrotoxicity of CP. The anti-nephrotoxic feature of the infusion may be attributed primarily to its anti-inflammatory and anti-apoptotic characteristics.
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http://dx.doi.org/10.1016/j.biopha.2019.108604DOI Listing
April 2019

Pathological Findings Observed in the Kidneys of Postnatal Male Rats Exposed to the 2100 MHz Electromagnetic Field.

Arch Med Res 2018 10 29;49(7):432-440. Epub 2018 Dec 29.

Department of Biochemistry, Recep Tayyip Erdogan University of Medical Faculty, Rize, Turkey.

Background: The widespread use by young people of modern communication devices such as mobile phones means that they are particularly exposed to electromagnetic fields (EMF) and other problems. However, few studies have researched the effects of long-term exposure to EMF in the kidney. We therefore investigated oxidative stress and apoptosis in long-term exposure to 2100 megahertz (MHz) in a rat model.

Materials And Methods: Twenty-four Sprague Dawley rats were divided into a control group (n = 8, no EMF exposure), a group exposed to 2100 MHz for 6 h for 30 d (n = 8), and a group exposed to 2100 MHz for12 h for 30 d (n = 8). Immunohistochemical analysis was performed, using caspase-3 to evaluate apoptosis. Immediately after treatment, reduced glutathione (GSH), malondialdehyde (MDA) in kidney tissue and serum levels of various biochemical compounds were measured to detect oxidative stress.

Results: Deterioration was observed in the brush border in renal tubules of the EMF groups. The results of the immunohistochemical analysis revealed a greater number of positively stained renal tubular epithelial cells in the EMF groups as compared with that in the control group. In the EMF groups, renal MDA levels increased, and renal GSH levels decreased compared with those in the control group, as shown by a biochemical examination (p = 0.00 and p = 0.00, respectively).

Conclusion: The findings showed that exposure to 2100 MHz for 6 and 12 h induced oxidative stress-mediated acute renal injury, depending on the length of exposure and dosage.
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http://dx.doi.org/10.1016/j.arcmed.2018.12.010DOI Listing
October 2018

An investigation of the effects of N-acetylcysteine on radiotherapy-induced testicular injury in rats.

Naunyn Schmiedebergs Arch Pharmacol 2019 02 13;392(2):147-157. Epub 2018 Nov 13.

Faculty of Medicine, Department of Histology and Embryology, Recep Tayyip Erdogan University, 53100, Rize, Turkey.

According to data issued by the International Agency for Research on Cancer in 2012, the estimated number of new cases of all types of cancer worldwide was estimated to exceed 10 million, and 6 million of whom receive radiotherapy. Radiotherapy is the treatment of cancer using ionizing radiation. Our study investigated the effects of x-radiation resulting from radiotherapy (RT) on the testis at the molecular level, and prospectively considered the potential protective characteristics of antioxidants against testicular damage resulting from x-radiation. Forty male Sprague Dawley rats were allocated into five groups, control (group 1), abdominopelvic region 2-Gy-ionizing radiation (group 2), whole-body 6-Gy irradiation (group 3), 2 Gy abdominopelvic region irradiation and 300 mg/kg NAC treatment (group 4), and 6-Gy whole-body irradiation and 300 mg/kg NAC treatment (group 5). Disorganization and vacuolization were observed in the epithelial layer in atrophic seminiferous tubules in the only ionizing radiation (IR) groups. In addition, Johnsen's score decreased in the only IR groups, while testis tissue malondialdehyde (MDA) and glutathione (GSH) tissue levels increased. N-Acetylcysteine (NAC) treatment groups Johnsen's score and tissue GSH levels increased than only IR groups. On the other hand, tissue MDA levels decreased in the NAC treatment groups. The findings showed that ionizing radiation caused apoptosis in germinal epithelial cells led to the oxidative stress-mediated testicular injury. On the other hand, NAC may be useful in the prevention of testicular injury-suppressed ROS production.
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http://dx.doi.org/10.1007/s00210-018-1581-6DOI Listing
February 2019

Effects of Gadodiamide and Gadoteric Acid on Rat Kidneys: A Comparative Study.

J Magn Reson Imaging 2019 02 13;49(2):382-389. Epub 2018 Sep 13.

Recep Tayyip Erdogan University Faculty of Medicine, Department of Biochemistry, Rize, Turkey.

Background: Gadolinium-based contrast agents are complex chelates to provide contrast in NRI. However, recent studies have highlighted the deposition of free Gd ion in various tissues.

Purpose: To evaluate the histopathological and immunohistochemical changes on rat kidney tissue following both macrocyclic (gadoteric acid) and linear (gadodiamide) agents under the hypothesis that gadolinium-based contrast agents (GBCA) lead to toxic, free Gd accumulation in tissues.

Study Type: The local Animal Care Committee approved the prospective animal study.

Animal Model: Thirty-two healthy Sprague-Dawley male rats were administered 2 mmol/kg gadodiamide and gadoteric acid for the first 4 days for 5 weeks. Group 1 received no drug (control, n = 8) and Group 2 (n = 8) was administered 0.1 ml/kg saline. Group 3 was administered 0.1 mmol/kg gadodiamide and Group 4 (n = 8) was administered 2 mmol/kg gadoteric acid.

Assessment: Biochemical, histopathological, and immunohistochemical changes in testis kidney tissue were evaluated at the end of 10 weeks.

Statistical Tests: Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by one-way analysis of variance and the Tamhane test, also followed by Turkey's HSD test.

Results: Gadolinium increased serum urea, Ca , and Caspase-3 positive tubular cell number. Larger Bowman capsules shrank proximal and distal tubules were revealed in the gadodiamide and gadoteric acid groups compared to the control group (P < 0.05). Histopathologic examination showed significantly more interstitial fibrosis, amyloid deposits, and vasocongestion in the gadodiamide group than the gadoteric acid and control groups, while the gadoteric acid group demonstrated significantly more leukocytic infiltration with atrophied proximal and distal tubules than the gadodiamide and control groups (P < 0.05).

Data Conclusion: GBCA administration causes significant histopathologic changes in kidney tissue. This study advocates additional investigation to assess the in vivo safety of GBCAs.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:382-389.
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http://dx.doi.org/10.1002/jmri.26266DOI Listing
February 2019

The protective effects of astaxanthin against cisplatin-induced retinal toxicity.

Cutan Ocul Toxicol 2019 Mar 9;38(1):59-65. Epub 2019 Jan 9.

b Department of Histology and Embryology, Faculty of Medicine , Recep Tayyip Erdogan University , Rize , Turkey.

Purpose: This study investigated the toxic effects of an antineoplastic agent, cisplatin (CIS), on retinal cells and the potential capacity of astaxanthin (ASTA) to elicit a future therapeutic protocol in CIS-induced retinal toxicity.

Materials And Methods: Six groups were formed for the assessment; control (healthy; Group 1), olive oil (olive oil only; Group 2), ASTA control group (ASTA only, Group 3), the single intraperitoneal (IP) dose of 16 mg/kg CIS (CIS only group; Group 4), 16 mg/kg CIS +25 mg/kg (IP) ASTA (Group 5), and 16 mg/kg CIS +75 mg/kg (IP) ASTA (Group 6). On the third day after CIS administration, rats in all groups were sacrificed under anesthesia and the analysis of the biochemical parameters and histopathological levels were performed.

Results: A significant decrease in GSH levels and increases in MDA, eNOS, and 8-OHdG expressions were recorded. Additionally, CIS treatment had caused acidophilic staining in retinal histological appearance. ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following CIS administration and increased the levels of GSH expressions, as well.

Conclusions: These results may suggest that the ASTA molecule as a promising option to prevent retinal toxicity in patients receiving CIS treatment for malignant tumors.
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http://dx.doi.org/10.1080/15569527.2018.1518330DOI Listing
March 2019

Whortleberry protects kidney against the cisplatin-induced nephrotoxicity: an experimental study.

Ren Fail 2018 Nov;40(1):466-474

g Biochemistry Department , Recep Tayyip Erdogan University School of Medicine , Rize , Turkey.

Purpose: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats.

Material And Methods: This study included 48 female Sprague-Dawley rats weighing 263.68 ± 8.29 g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16 mg/kg cisplatin +100 mg/kg whortleberry, and 16 mg/kg cisplatin +200 mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (μm), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p < .05 was considered statistically significant.

Results: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p < .05). Treatment with 100 and 200 mg whortleberries increased the total antioxidant status; decreased the total oxidant status and Caspase-3 level and ameliorated distal and proximal tubule degeneration, glomerular degeneration and edema in the kidney tissues (p < .05).

Conclusions: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.
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http://dx.doi.org/10.1080/0886022X.2018.1500292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104611PMC
November 2018