Hydroalcoholic extract of zataria multiflora mitigates cisplatin-induced oxidative stress, apoptosis and hepatotoxicity in mice

Abstract

Cisplatin (CP), as an anticancer drug, causes hepatotoxicity. Zataria multiflora Boiss (ZM), as a herbal medicine, has antioxidant property and decrease oxidative stress-induced toxicity and side effects. This study investigated the effects of hydroalcoholic extract of ZM against cisplatin-induced hepatotoxicity. In this experimental study, thirty-two male mice were randomly divided into four groups (8/group). The control group; ZM group was received ZM (200 mg/kg) during 7 days by gavage; CP group was received CP (10 mg/kg) intraperitoneally in 5th day of study; ZM + CP group. Serum biochemical [alanine aminotransferases (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP)], tissue biochemical [malondialdehyde (MDA), protein carbonyl (PC) and glutathione (GSH) content], histopathological and immunohistochemical assays were examined to determine hepatotoxicity. CP caused significant increase in ALT, AST and ALP, oxidative stress (increased of MDA, PC and decreased of GSH in liver tissues), histological changes (hepatocellular degeneration, necrosis, inflammatory cell infiltration, congestion, sinusoidal dilatation). ZM significantly mitigated the toxic effects of CP on the liver tissue and oxidative stress (p<0.01 and p<0.05, respectively). Furthermore, CP increased caspase-3 immunoreactivity (apoptosis) (21.85 ± 6.81) and ZM administration significantly reduced immunoreactivity of caspase-3 compared with CP-treated mice (10.66 ± 3.23). The findings of this study showed that the ZM as a potential antioxidant compound and with scavenging free radicals, hepatic injury and suppression of caspase-3 expression attenuated the hepatotoxicity induced cisplatin.