Effects of vitamin d3 on ppar-α and its target gene nfkbia on a rat model of high carbohydrate high fat diet induced non alcoholic steatohepatitis | ||||
| Bulletin of Egyptian Society for Physiological Sciences | ||||
| Article 4, Volume 35, Issue 2, December 2015, Page 86-105 PDF (1.78 MB) | ||||
| Document Type: Original Article | ||||
| DOI: 10.21608/besps.2015.34482 | ||||
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| Authors | ||||
| Mohamed El-Dosoky* 1; Sally Abed2; Mohamed Elshafey3 | ||||
| 1Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt | ||||
| 2Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Egypt | ||||
| 3Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Egypt | ||||
| Abstract | ||||
| Accumulating data suggesting that Vitamin D3 could be of a potential therapeutic value for non-alcoholic fatty liver disease (NAFLD) ,but its underlying mechanisms are still under research .Vitamin D3 up regulates PPAR-α and downstream gene nuclear factor-kappa-B inhibitor subunit-alpha (NFKBIA) which may represent a novel strategy for the management of NASH. Therefore, in this study, we investigated the possible protective role of vitamin D3 on high carbohydrate high fat diet (HCHFD) animal model of NASH through PPAR-α and NFKBIA pathway Methods: Thirty male Sprague-Dawley rats were equally divided into three groups; group I: (negative control group) fed standard rat chow diet for 8 weeks. group II: received HCHFD for 8 weeks. group III: fed as group II for 8 weeks and received also, I.P administration of vitamin D3 at a dose of 5 μg/kg twice weekly from the fourth week till the end of the study. At the end of the experiment, serum triglycerides, total cholesterol, liver enzymes, serum albumin, serum bilirubin and liver tissue oxidative stress markers (MDA, SOD and GSH) were measured. Hepatic histopathological alterations were assessed by hematoxylin and eosin, Masson’s trichrome, and Oil Red O staining ; the expressions of NF-κ B p65 (ReIA) was estimated in liver tissues using immunohistochemistry and the expression of hepatic PPAR-α and NFKBIA genes were estimated at the level of mRNA by quantitative real-time PCR. Results: Nonalcoholic steatohepatitis (NASH) model was confirmed by histopathological examination as indicated by elevated NAFLD activity score (NAS) as well as elevation of serum liver enzymes , hyperlipidemia in the form elevated plasma triglycerides and total cholesterol, oxidative stress state (high MDA, low GSH and SOD) and down regulation of PPAR-α and NFKBIA mRNA in liver tissues which was concomitant with up regulation of inflammatory marker NF-κ B-p65(ReIA) . On the other hand, vitamin D3 ameliorated NASH by attenuation of oxidative stress (low MDA, high GSH and SOD) and up regulation of PPAR-α and NFKBIA genes at the level of mRNA in the liver tissues which was accompanied by decrease in hepatocyte nuclear NF-κ B-p65 (ReIA) immunohistochemical brownish staining. Conclusion: Vitamin D3 attenuates NASH in HCHFD rat model by attenuation of redox state and up regulation of PPAR-α and its downstream gene NFKBIA in liver tissues. | ||||
| Keywords | ||||
| vitamin D3; HCHFD; Nonalcoholic; Steatohepatitis; PPAR-α; NFKBIA | ||||
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