Protective Effects of Carvacrol Against Methotrexate-induced Liver Toxicity in Rats.

ABSTRACT

BACKGROUND: To investigate whether carvacrol (CAR) pretreatment reduces the severity of methotrexate (MTX)-induced hepatotoxicity in rats. METHODS: A total of 24 rats were equally divided into three groups group I, control ; group II, MTX-treated ; and group III, CAR+MTX-treated. On Day 1 group III received a one-time intraperitoneal dose of CAR (73 mg/kg), and on Day 2 both groups II and III received a single dose of intraperitoneal MTX (20 mg/kg). The rats were then sacrificed so to harvest blood and liver tissue samples to determine malondialdehyde (MDA), total antioxidant capacity (TAS), total oxidant status (TOS), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels. Histological specimens were examined via light microscopy. RESULTS: Levels of MDA, ALT, AST and ALP in rat liver tissue samples were significantly higher in the MTX-treated group relative to the control group. However, TAS was significantly reduced in the MTX-treated group when compared to controls. Pretreating rats with CAR counteracted the effect of MTX exposure as MDA was significantly decreased and TAS was elevated in liver tissues when contrasted with the MTX-treated group. Furthermore, histological examination demonstrated significant liver injury in the MTX-treated group versus the CAR+MTX group. CONCLUSIONS: Pretreatment with CAR markedly diminished liver damage induced by MTX. Therefore, CAR administration preceding MTX treatment might be a promising therapeutic modality to prevent and/or lessen the extent of MTX-induced hepatotoxicity.