Pantothenic Acid Derivatives Modulate Oxidative Stress and Hepatic Fibrosis in Bile Duct Ligation-Induced Cholestatic Liver Injury.

BACKGROUND/

OBJECTIVES

Inflammation and oxidative stress are key factors contributing to the initiation and progression of liver fibrosis in chronic obstructive cholestasis. Pantothenic acid (PA) and some of its derivatives have been reported to exhibit moderate anti-inflammatory, antioxidant, and regenerative effects. This study aimed to evaluate the redox-modulating effects of PA derivatives-panthenol (PL), pantethine (PT), and hopantenic acid (HPA) in a rat model of chronic obstructive cholestasis induced by common bile duct ligation (BDL).

METHODS

Macroscopic, histological, and ultrastructural alterations in the liver were assessed, along with molecular markers of oxidative stress, inflammation, and parameters of the glutathione (GSH) system.

RESULTS

BDL-induced liver injury was associated with enhanced lipid peroxidation, mitochondrial structural alterations, depletion of GSH, increased levels of protein S-glutathionylation (PSSG), and elevated thiobarbituric acid-reactive substances in mitochondria. Treatment with PL and, to a lesser extent, PT was associated with attenuation of hepatocellular ultrastructural damage, reduced bile duct hyperplasia, decreased inflammatory and necrotic changes, and moderate improvement in fibrosis-related parameters. In contrast, HPA (a PA antagonist) did not demonstrate hepatoprotective effects and it was associated with more pronounced liver injury.

CONCLUSIONS

Chronic BDL is accompanied by suppression of glutathione redox capacity and enhanced oxidative stress. PL and PT, but not HPA, were associated with reduced levels of protein S-glutathionylation and partial restoration of redox balance. The protective effects of PL and PT may contribute to their antifibrotic activity, potentially through direct antioxidant capacity or redox-modulating mechanisms associated with the GSH system.