vitamin-u and Chemical-and-Drug-Induced-Liver-Injury--Chronic

The aim of this study was to investigate the cellular mechanisms that cause valproic acid (VPA)-induced liver damage and the therapeutic effect of Vitamin U (Vit U) on these mechanisms. Female Sprague Dawley rats were randomly divided into four groups: intact control animals, animals that received Vit U (50 mg/kg/day), animals given VPA (500 mg/kg/day), and animals given both VPA and Vit U. The rats in the Vit U + VPA group were administered Vit U by gavage an hour before VPA administration every day for 15 days. Liver tissues were evaluated through histopathological, biochemical, immunohistochemical, and Western blotting techniques. Administration of Vit U with VPA resulted in (i) prevention of histopathological changes caused by VPA; (ii) blockage of the decrease in catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities; prevention of the elevation in gamma-glutamyl transferase (GGT) activity and advanced oxidation protein products (AOPP) level; (iii) increased in the levels of interleukin-1 beta (IL-1β), active caspase-3, and cytoplasmic cytochrome c; (iv) increase in cleaved poly (ADP-ribose) polymerase (PARP) level and decrease in LC3B (II/I) ratio; (v) increase in the number of proliferating cells nuclear antigen (PCNA) positive hepatocytes. These findings show that Vit U prevents liver damage caused by VPA through increasing the antioxidant enzyme capacity and hepatocyte proliferation by triggering inflammation and apoptosis. These findings suggest that Vit U provides its protective effects against VPA-induced liver damage by stimulating homeostasis and regeneration.

Topics: Animals; Antioxidants; Apoptosis; Cell Proliferation; Chemical and Drug Induced Liver Injury, Chronic; Female; Hepatocytes; Inflammation; Oxidative Stress; Rats; Rats, Sprague-Dawley; Valproic Acid; Vitamin U