Water Extract of Ash Tree (Fraxinus rhynchophylla) Leaves Protects against Paracetamol-Induced Oxidative Damages in Mice

The protective effect of water extract of ash tree leaves (ALE) against oxidative damages was investigated in paracetamol-induced BALB/c mice. Biochemical analysis of anti-oxidative enzymes, immunoblot analyses of hepatic cytochrome P450 2El (CYP2E1), and the gene expression of tumor necrosis factor (TNF-${\alpha}$) were examined to determine the extract's protective effect and its possible mechanisms. BALB/c mice were divided into three groups: normal, paracetamol-administered, and ALE-pretreated groups. A single dose of paracetamol led to a marked increase in lipid peroxidation as measured by malondialdehyde (MDA). This was associated with a significant reduction in the hepatic antioxidant system, e.g., glutathione (GSH). Paracetamol administration also significantly elevated the expression of CYP2E1, according to immunoblot analysis, and of TNF-${\alpha}$ mRNA in liver. However, ALE pretreatment prior to the administration of paracetamol significantly decreased hepatic MDA levels. ALE restored hepatic glutathione and catalase levels and suppressed the expression of CYP2E1 and TNF-${\alpha}$ observed in inflammatory tissues. Moreover, ALE restored mitochondrial ATP content depleted by the drug administration. These results show that the extract of ash tree leaves protects against paracetamol-induced oxidative damages by blocking oxidative stress and CYP2E1-mediated paracetamol bioactivation.