Protective Effect of Thyme Honey against Valproic Acid Hepatotoxicity in Wistar Rats

INTRODUCTION: Valproic acid is a medication most commonly used in the treatment of emotional and neurological depression, psychological imbalances, epilepsy, and bipolar disorder. Dark honey, like thyme honey, contains more antioxidant compounds than other samples. The purpose of this study was to evaluate the effect of thyme honey on the potential hepatic effects of valproic acid. METHODS: In this study, 48 male rats were randomly divided into 8 groups (n = 6): G1 (control): healthy rats (normal saline 0.9%), G2: thyme honey (1 g/kg), G3: thyme honey (2 g/kg dose), G4: thyme honey (3 g/kg dose), G5: VPA (500 mg/kg), G6: VPA (500 mg/kg) and thyme honey (1 g/kg), G7: VPA (500 mg/kg) and thyme honey (2 g/kg dose), and G8: VPA (500 mg/kg) and thyme honey (3 g/kg dose). Groups G1 to G5 received the drug for 28 days. On day 14, administration of thyme honey for G6 to G8 groups was carried out using gavage until day 28. VPA was administered one hour after honey. To carry out the biochemical evaluation, blood samples were collected from all the groups and their serums were used for MDA, TAC, and liver enzymes (AST, ALT, and GGT). Tissue samples of each rat were also removed for histological studies with hematoxylin-eosin and Masson's trichrome staining. RESULTS: The use of thyme honey significantly improved the histopathological parameters of the liver tissue, including hypertrophic degeneration and nucleus alteration, expansion of sinusoids, fibrosis and hepatic necrosis, and inflammation as well as hypertrophy of Kupffer cells. In the groups receiving VPA, the rate of lipid peroxidation increased, which indicates the destruction of the liver cell membrane due to drug consumption. TAC levels also increased following increase in thyme honey dosage (p ≤ 0.05). The results of liver enzyme analysis showed a decrease in AST and ALT levels in the G6 group and a decrease in GGT level in the G8 group (p ≤ 0.05). CONCLUSION: Based on the results of this study, it seems that high percentage of antioxidants in thyme honey enabled it to improve hepatic complications and reduce the rate of hepatocellular destruction.