Vitamin D3 abates BDL-induced cholestasis and fibrosis in rats via regulating Hedgehog pathway

Toxicology and Applied Pharmacology
Noha Abdel-RahmanMohammed S El-Awady

Abstract

Liver cholestasis is a complex disease of broad etiologies. Hedgehog (Hh) signaling has been shown to play a pivotal role in modulating liver repair post cholestatic liver injury. We here investigated the role of vitamin D in experimental liver cholestasis induced by bile-duct ligation (BDL) in rats. Male Sprague Dawley rats underwent BDL surgery and two weeks post-surgery; vitamin D was administered daily for two weeks. Serum markers of hepatocellular integrity were measured and fibrosis was detected by measuring α-SMA and hepatic TGF-β1 as well as hepatic collagen content. Hh signaling was evaluated by measuring Smo and Gli1 levels. Histopathological examination of hepatic tissue was performed. Vitamin D alleviated obstructive cholestatic damage as illustrated by total bilirubin as well as gamma glutamyl transferase (γ-GT) serum levels. It also alleviated hepatocellular damage as suggested by reducing elevated serum aminotransferases induced by BDL. Antifibrotic activity of vitamin D was confirmed by decrease in mRNA and protein expression of α-SMA, as well as collagen content in hepatic tissue. Furthermore, vitamin D suppressed BDL-induced elevated hepatic TGF-β1 mRNA and protein levels. BDL activated Hh signaling and upregu...Continue Reading

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Dec 15, 2020·Chemico-biological Interactions·Wanyi LuJuan Kong

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