Protective Effects of Eugenol against Hepatotoxicity Induced by Arsenic Trioxide: An Antileukemic Drug

BACKGROUND: Arsenic trioxide (As2O3) has shown effectiveness in the treatment of leukemia, but it is also associated with hepatotoxicity. Given antileukemic drug-induced oxidative stress and toxicity, this study focused on the mitigatory role of eugenol, a monoterpene compound from clove oil, in the hepatic tissue of Wistar rats. METHODS: Twenty-four male Wistar rats (180-250 g) were randomly divided into 4 groups (6 rats per group): normal control rats, rats treated with As(2)O(2) (4 mg/kg bwt), rats treated with eugenol (5 mg/kg bwt), and rats receiving co-treatment with As(2)O(3) (4 mg/kg bwt) and eugenol (5 mg/kg bwt), all of which orally administered for a period of 30 days. The Tukey test (Origin version 7, Origin Lab Corporation, Northampton, USA) was applied to analyze the one-way analysis of variance (ANOVA) between the different groups. A P value less than 0.05 was considered significant. RESULT: Oral administration of As2O3 significantly induced hepatic damage, evident from increased levels of aspartate transaminase and alanine transaminase (P=0.01 and P<0.001, respectively). Moreover, a decrease in the activities of enzymatic and nonenzymatic antioxidants altered electrolyte concentration and increased the rate of lipid peroxidation (P=0.04) and the level of nitric oxide (P=0.01). Accumulation studies and histopathological analyses confirmed the biochemical variations. Co-treatment with eugenol (5 mg/kg bwt) exhibited hepatoprotective effects as manifested by the decreased rate of arsenic accumulation, lipid peroxidation, and nitric oxide level along with normalized levels of antioxidants and maintained histology of the liver. CONCLUSION: Eugenol may be used in combination with arsenic trioxide in chemotherapy to reduce oxidative damage to the hepatic system.