Publications by authors named "Mansur A Sandhu"

10 Publications

  • Page 1 of 1

The Combined Influence of Magnesium and Insulin on Central Metabolic Functions and Expression of Genes Involved in Magnesium Homeostasis of Cultured Bovine Adipocytes.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Institute of Veterinary Physiology, Freie Universität Berlin, 14163 Berlin, Germany.

At the onset of lactation, dairy cows suffer from insulin resistance, insulin deficiency or both, similar to human diabetes, resulting in lipolysis, ketosis and fatty liver. This work explored the combined effects of different levels of magnesium (0.1, 0.3, 1 and 3 mM) and insulin (25, 250 and 25,000 pM) on metabolic pathways and the expression of magnesium-responsive genes in a bovine adipocyte model. Magnesium starvation (0.1 mM) and low insulin (25 pM) independently decreased or tended to decrease the accumulation of non-polar lipids and uptake of the glucose analog 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-6-deoxyglucose (6-NBDG). Activity of glycerol 3-phosphate dehydrogenase (GPDH) was highest at 25 pM insulin and 3 mM magnesium. Expression of and was reduced at 0.1 mM magnesium either across insulin concentrations () or at 250 pM insulin (). expression was reduced at 3 mM magnesium. expression was reduced at 3 mM and 0.1 mM magnesium at 25 and 250 pM insulin, respectively. Expression of , , and was not affected. We conclude that magnesium promotes lipogenesis in adipocytes and inversely regulates the transcription of genes that increase vs. decrease cytosolic magnesium concentration. The induction of GAPDH activity by surplus magnesium at low insulin concentration can counteract excessive lipomobilization.
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http://dx.doi.org/10.3390/ijms22115897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199494PMC
May 2021

Optimizing adipogenic transdifferentiation of bovine mesenchymal stem cells: a prominent role of ascorbic acid in induction.

Adipocyte 2020 12;9(1):35-50

Institute of Veterinary-Physiology, Freie Universität Berlin, Berlin, Germany.

Adipocyte differentiation of bovine adipose-derived stem cells (ASC) was induced by foetal bovine serum (FBS), biotin, pantothenic acid, insulin, rosiglitazone, dexamethasone and 3-isobutyl-1-methylxanthine, followed by incubation in different media to test the influence of ascorbic acid (AsA), bovine serum lipids (BSL), FBS, glucose and acetic acid on transdifferentiation into functional adipocytes. Moreover, different culture plate coatings (collagen-A, gelatin-A or poly-L-lysine) were tested. The differentiated ASC were subjected to Nile red staining, DAPI staining, immunocytochemistry and quantitative reverse transcription PCR (for ). Nile red quantification showed a significant increase in the development of lipid droplets in treatments with AsA and BSL without FBS. The presence of BSL induced a prominent increase in mRNA abundance and in FABP4 immunofluorescence signals in coincubation with AsA. The abundance of and mRNA decreased or tended to decrease in the absence of FBS, and ENG was additionally suppressed by AsA. DAPI fluorescence was higher in cells cultured in poly-L-lysine or gelatin-A coated wells. In additional experiments, the multi-lineage differentiation potential to osteoblasts was verified in medium containing ß-glycerophosphate, dexamethasone and 1,25-dihydroxyvitamin D using alizarin red staining. In conclusion, bovine ASC are capable of multi-lineage differentiation. Poly-L-lysine or gelatin-A coating, the absence of FBS, and the presence of BSL and AsA favour optimal transdifferentiation into adipocytes. AsA supports transdifferentiation via a unique role in induction, but this is not linearly related to the primarily BSL-driven lipid accumulation.: AcA: acetic acid; AsA: ascorbic acid; ASC: adipose-derived stem cells; BSL: bovine serum lipids; DAPI: 4´,6-diamidino-2-phenylindole; DLK: delta like non-canonical notch ligand; DMEM: Dulbecco's modified Eagle's medium; DPBS: Dulbecco's phosphate-buffered saline; ENG: endoglin; FABP: fatty acid binding protein; FAS: fatty acid synthase; GLUT4: glucose transporter type 4; IBMX: 3-isobutyl-1-methylxanthine; LPL: lipoprotein lipase; MSC: mesenchymal stem cells; α-MEM: α minimum essential medium; NT5E: ecto-5'-nucleotidase; PDGFRα: platelet derived growth factor receptor α; PPAR: peroxisome proliferator activated receptor γ; RPS19: ribosomal protein S19; SEM: standard error of the mean; THY1: Thy-1 cell surface antigen; TRT: treatment; TRT-Con: treatment negative control; YWHAZ: tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta.
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http://dx.doi.org/10.1080/21623945.2020.1720480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999845PMC
December 2020

Modulating Oxidative Stress in Drug-Induced Injury and Metabolic Disorders: The Role of Natural and Synthetic Antioxidants.

Oxid Med Cell Longev 2019;2019:3206401. Epub 2019 Jun 27.

Cardiovascular Science, The Centre for Bioscience, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.

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http://dx.doi.org/10.1155/2019/3206401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620855PMC
January 2020

Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health.

Oxid Med Cell Longev 2019 10;2019:5484138. Epub 2019 Mar 10.

Physiology Division, Department of Zoology, Faculty of Science, Beni-Suef University, Egypt.

The prevalence of cardiovascular disease (CVD) is increasing over time. CVD is a comorbidity in diabetes and contributes to premature death. Citrus flavonoids possess several biological activities and have emerged as efficient therapeutics for the treatment of CVD. Citrus flavonoids scavenge free radicals, improve glucose tolerance and insulin sensitivity, modulate lipid metabolism and adipocyte differentiation, suppress inflammation and apoptosis, and improve endothelial dysfunction. The intake of citrus flavonoids has been associated with improved cardiovascular outcomes. Although citrus flavonoids exerted multiple beneficial effects, their mechanisms of action are not completely established. In this review, we summarized recent findings and advances in understanding the mechanisms underlying the protective effects of citrus flavonoids against oxidative stress, inflammation, diabetes, dyslipidemia, endothelial dysfunction, and atherosclerosis. Further studies and clinical trials to assess the efficacy and to explore the underlying mechanism(s) of action of citrus flavonoids are recommended.
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http://dx.doi.org/10.1155/2019/5484138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431442PMC
July 2019

Umbelliferone prevents oxidative stress, inflammation and hematological alterations, and modulates glutamate-nitric oxide-cGMP signaling in hyperammonemic rats.

Biomed Pharmacother 2018 Jun 22;102:392-402. Epub 2018 Mar 22.

Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt; Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt. Electronic address:

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication that occurs as a result of liver failure. Umbelliferone (UMB; 7-hydroxycoumarin) is a natural product with proven hepatoprotective activity; however, nothing has yet been reported on its protective effect against hyperammonemia, the main culprit behind the symptoms of HE. Here, we evaluated the effect of UMB against ammonium chloride (NHCl)-induced hyperammonemia, oxidative stress, inflammation and hematological alterations in rats. We demonstrated the modulatory role of UMB on the glutamate-nitric oxide (NO)-cGMP pathways in the cerebrum of rats. Rats received intraperitoneal injections of NHCl (3 times/week) for 8 weeks and concomitantly received 50 mg/kg UMB. NHCl-induced rats showed significantly elevated blood ammonia and liver function markers. Lipid peroxidation and NO were increased in the liver and cerebrum of rats while the antioxidant defenses were declined. UMB significantly reduced blood ammonia, liver function markers, lipid peroxidation and NO, and enhanced the antioxidant defenses in NHCl-induced rats. UMB significantly prevented anemia, leukocytosis, thrombocytopenia and prolongation of PT and aPTT. Hyperammonemic rats showed elevated levels of cerebral TNF-α, IL-1β and glutamine as well as increased activity and expression of Na/K-ATPase, effects that were significantly reversed by UMB. In addition, UMB down-regulated nitric oxide synthase and soluble guanylate cyclase in the cerebrum of hyperammonemic rats. In conclusion, this study provides evidence that UMB protects against hyperammonemia via attenuation of oxidative stress and inflammation. UMB prevents hyperammonemia associated hematological alterations and therefore represents a promising protective agent against the deleterious effects of excess ammonia.
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http://dx.doi.org/10.1016/j.biopha.2018.03.104DOI Listing
June 2018

Effects of dietary chromium supplementation on muscle and bone mineral interaction in broiler chicken.

J Trace Elem Med Biol 2017 Jul 15;42:25-29. Epub 2017 Mar 15.

Department of Livestock Production and Management, Faculty of Veterinary and Animal Sciences, PMAS-Arid Agriculture University, Rawalpindi, Pakistan.

The study was conducted to ascertain the effects of dietary chromium chloride (CrCl·6HO) supplementation on mineral interaction in blood serum, leg muscles and bones of broilers at 35 day of age. For this purpose, ninety male broiler chicks were divided into three groups. One served as control (group I) while, the other two groups were supplemented with CrCl (group II-12.5mg/Kg feed; group III-25mg/Kg feed) from 12 to 28days of age. In serum, Cr concentration remained non-significant however, Zn, and K concentrations decreased (P<0.05) with both levels of Cr-supplementation. Furthermore, in muscles Cr, Cu, Ca and Na levels remained non-significant but concentrations of Zn and K decreased (P<0.05) with feed Cr enrichment. Chromium had a substantial effect on femur and fibula Zn retention with 25mg/Kg feed supplementation while, Cr deposition decreased (P<0.05) in fibula. Femur Ca (P<0.002), Na (P<0.001) and K (P<0.05) retention was inversely proportional to both Cr concentrations in feed. In tibia, Cu and Na concentration decreased (P<0.002) with high dietary Cr supplementation. Fibular Ca and Na concentrations remained significantly (P<0.001) lower in Cr supplemented groups. Bone robusticity index was non-significant but ash to weight ratio of femur, tibia and fibula decreased (P<0.05) in group III. Chromium supplementation has a major effect on serum or muscle Zn and K deposition while bone mineral interaction shows a major thrust on Zn, Ca and Na levels.
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http://dx.doi.org/10.1016/j.jtemb.2017.03.007DOI Listing
July 2017

Influence of Bovine Serum Lipids and Fetal Bovine Serum on the Expression of Cell Surface Markers in Cultured Bovine Preadipocytes.

Cells Tissues Organs 2017 12;204(1):13-24. Epub 2017 May 12.

Institute of Veterinary Physiology, Free University of Berlin, Berlin, Germany.

To establish the influence of fetal bovine serum (FBS) and bovine serum lipids (BSL) on cell differentiation marker expression, bovine adipose-derived stem cells from subcutaneous tissue were incubated for 14 days in 4 types of differentiation media containing 10% FBS and 10 µL/mL BSL (TRT-1), no FBS and 10 µL/mL of BSL (TRT-2), 10% FBS and no BSL (TRT-3), or no supplements (TRT-4). Cells were subjected to Nile red staining, immunocytochemistry (CD73, CD90, CD105, DLK1, FabP4), and quantitative real-time PCR (CD73, CD90, CD105, FabP4). The number of cells presenting FabP4 and the percentage of mature adipocytes with large lipid droplets were increased in TRT-2, accompanied by a robust increase in FabP4 mRNA abundance and a decrease in DLK1-positive cells. In preadipocytes, CD73 was present around the nucleus and translocated towards cell membranes during differentiation. Although the percentage of CD73-positive cells was not different among treatments, its mRNA abundance, immunocytochemical staining intensity, and translocation towards cell membranes were decreased when the medium contained no FBS (TRT-2 and TRT-4). All cells showed a diffuse distribution of CD90 and CD105 and remained positive for these markers irrespective of the treatment. However, the CD90 and CD105 mRNA abundance was decreased in TRT-2 and TRT-4; i.e., in media containing no FBS. The presence of FBS increased the absolute number of cell nuclei as assessed by DAPI fluorescence. Our results suggest that bovine subcutaneous preadipocytes display typical stem cell markers. The differentiation into mature adipocytes is promoted by BSL, whereas FBS endorses cell proliferation.
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http://dx.doi.org/10.1159/000472708DOI Listing
March 2018

Empirical evidence of cold stress induced cell mediated and humoral immune response in common myna (Sturnus tristis).

Int J Biometeorol 2015 Nov 7;59(11):1607-13. Epub 2015 Feb 7.

Department of Zoology, PMAS-Arid Agriculture University, Rawalpindi, 46300, Pakistan.

Common myna (Sturnus tristis) is a bird indigenous to the Indian subcontinent that has invaded many parts of the world. At the onset of our investigation, we hypothesized that the immunological profile of myna makes it resistant to harsh/new environmental conditions. In order to test this hypothesis, a number of 40 mynas were caught and divided into two groups, i.e., 7 and 25 °C for 14 days. To determine the effect of cold stress, cell mediated and humoral immune responses were assessed. The macrophage engulfment percentage was significantly (P < 0.05) higher at 25 °C rather than 7 °C either co-incubated with opsonized or unopsonized sheep red blood cells (SRBC). Macrophage engulfment/cell and nitric oxide production behaved in a similar manner. However, splenic cells plaque formation, heterophil to lymphocyte (H/L) ratio, and serum IgM or IgG production remained non-significant. There was a significant increase of IgG antibody production after a second immunization by SRBC. To the best of our knowledge, these findings have never been reported in the progression of this bird's invasion in frosty areas of the world. The results revealed a strengthened humoral immune response of myna and made this bird suitable for invasion in the areas of harsh conditions.
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http://dx.doi.org/10.1007/s00484-015-0967-0DOI Listing
November 2015

Genotoxicity evaluation of chlorpyrifos: a gender related approach in regular toxicity testing.

J Toxicol Sci 2013 ;38(2):237-44

Department of Veterinary Biomedical Sciences, Faculty of Veterinary and Animal Sciences, PMAS, Arid Agriculture University, Pakistan.

The oral intubation of chlorpyrifos, an extensively used organophosphate insecticide, was tested for its capability to induce in vivo genotoxic upshot in blood lymphocytes of 24 male and female Wistar rats using biomarker of genotoxicity. Rats were orally administered with daily doses 3 and 12 mg/kg body weight (BW) of chlorpyrifos (CPF). The blood lymphocytes were harvested after 7 and 14 days of treatment and subjected to bi-nucleus (BN), multi-nucleus (MN) and single cell gel electrophoresis (comet assay) to evaluate the extent of DNA damage. Other than BN and MN assay, damage to DNA was assessed through comet length, height, area, head diameter, head DNA percentage and tail DNA percentage along with tail movement. A significant boost was noticed in the frequency of BN cells formation after 12 mg/kg BW CPF treatment. However, the propensity to produce MN cells was significantly more (P ≤ 0.05) in males than that of females. Likewise, the frequency of comet formation, mean comet length, height and area were more (P ≤ 0.05) in males than females even with 12 mg/kgBW. Comet head DNA % and tail length remained non-significant. Olive movement also revealed a significant increase (P ≤ 0.05) in males than females. The study inferred that the CPF can induce DNA damage in both male and female subjects but more pronounced in the male individuals.
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http://dx.doi.org/10.2131/jts.38.237DOI Listing
September 2013

Dynamics of innate immune response in Gallus domesticus using two methods of induced molting.

Vet Immunol Immunopathol 2007 Dec 22;120(3-4):106-14. Epub 2007 Jun 22.

Department of Physiology and Pharmacology, University of Agriculture, Faisalabad 38040, Punjab, Pakistan.

The aim of this study was to compare the ability of laying hen abdominal macrophages during the second production cycle by using two different methods of induced molting. Two groups of Single Comb White Leghorn hens were induced to molt at the end of their first production cycle using feed restriction and ZnO supplementation. Macrophages were isolated from the abdomen and in vitro cytotoxic ability, at which point macrophage bactericidal moiety nitric oxide (NO) was recorded. Serum IgM and IgG titers against sheep red blood cells (SRBC) were determined at various stages: before molting (BM), 5% production level (5P), peak production stage (PP) and at the end of production (EP) level after fast and Zn-induced molt. Macrophages adherence percentage remained unaffected (p< or =0.05) during all production cycles, whereas the macrophage engulfment percentage and engulfment/cell was significantly higher (p< or =0.05) at PP in both fast and Zn-induced molted groups, as compared to all other studied stages. Macrophage NO production was increased (p< or =0.05) at PP and after SRBC and lipopolysaccrides (LPS) stimulus, when molted with ZnO supplementation. Serum total antibody titer against SRBC increased serum IgG and IgM titers during the second production cycle by Zn-induced molt. However, molting stress greatly reduced IgG and IgM production at the 5P stage. Serum Zn concentration increased with the onset of production but decreased at the EP stage irrespective of their molting regimes. Our results validate the strengthened innate and acquired immune response during the second production cycle after Zn-induced molting instead of fasting.
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http://dx.doi.org/10.1016/j.vetimm.2007.06.020DOI Listing
December 2007
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