Hepatoprotective effect of chitosan-vitamin C based hydrogel on alpha-Naphthylisothiocyanate-induced cholestasis in infant rats.

BACKGROUND

Infant cholestasis is characterized by the buildup of biliary substances in blood and extrahepatic tissues because of impaired canalicular biliary flow, which harm the liver and bile ducts. Vitamin C (Vit C) is antioxidant which has demonstrated encouraging outcomes in the treatment of different liver disorders, including fibrosis.

AIM: The present study seeks to assess the synergistic protective effect of chitosan and vitamin C based hydrogel (CSVC hydrogel) on alpha-Naphthylisothiocyanate (ANIT)-induced cholestasis in infant rats.

METHOD: Thirty male Wister rats were divided into five groups: control, ANIT, and cholestatic rats treated with chitosan hydrogel (60 mg/kg body weight, orally), Vit C (40 mg/kg body weight, orally), and CSVC hydrogel (60 mg/kg body weight, orally). Liver functions, oxidative stress, inflammatory, and apoptotic markers were investigated.

RESULTS

CSVC hydrogel had remarkable antioxidant and anti-inflammatory properties in vitro. The administration of CSVC hydrogel significantly improved liver function, evidenced by decreased hepatic enzyme activity such as AST (28.11 ± 0.83###), ALT (16.56 ± 0.95###), ALP (126.49 ± 3.06###), GGT (0.11 ± 0.02###), total bilirubin (1.71 ± 0.05###) and a rise in albumin levels to 3.11 ± 0.10###. Moreover, CSVC hydrogel resulted in an increase in reduced glutathione and the activity of antioxidant enzymes (GST, SOD, GPx, and catalase), while simultaneously decreasing the production of malondialdehyde and nitric oxide. CSVC hydrogel decreased DNA damage in cholestatic rats and partially corrected the abnormal structure of hepatic tissues in ANIT rats. CSVC hydrogel decreased inflammation by decreasing concentrations of interleukin 6 (IL-6) and interleukin 1β (IL-1β) while enhancing the antiapoptotic protein BCL2. The immunohistochemistry analysis revealed a reduction in inflammation and apoptosis, through the decreased production of tumor necrosis factor alpha (TNF-α) and Caspase 3.

CONCLUSION

CSVC hydrogel mitigated liver fibrosis via its anti-inflammatory, anti-apoptotic, antioxidant properties, and its DNA protective effects.