Elecampane rhizome extract alleviates methotrexate-induced hepatotoxicity and nephrotoxicity in male rats

Methotrexate (MTX) is a chemotherapy drug used to treat cancer and inflammatory diseases; however, its clinical applicability is limited due to its cytotoxic nature. The present study tested elecampane (Inula helenium L.) rhizome extract (ERE) for its protective effects against MTX-induced hepatotoxicity and nephrotoxicity in male rats. The rats were divided into five experimental groups (n = 10): control (physiological saline); MTX, physiological saline, and MTX [40 mg/kg intraperitoneal (i.p.)] on the fourth day; and three groups in which rats concurrently received MTX plus three doses of ERE (100, 200, 400 mg/kg) orally for 10 consecutive days. The findings revealed that MTX administration substantially elevated serum concentrations of total cholesterol (TC), low-density lipoproteins cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen, and creatinine. Additionally, it increased malondialdehyde (MDA), interleukin-1β (IL-1β), and tumor necrotic factor-α (TNFα) levels in the liver and renal tissues while decreasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. However, treatment with ERE at a dosage of 400 mg/kg reversed the adverse effects of MTX toxicity by decreasing the levels of TC, LDL-C, MDA, AST, ALT, ALP, IL-1β, TNFα and increasing the activities of GPx, CAT, and SOD in the tissues mentioned above. A histological examination of the liver and renal tissues also confirmed the ameliorating effects of ERE. The present study indicated that EER could inhibit MTX-induced hepatotoxicity and nephrotoxicity by improving antioxidant defense and decreasing oxidative stress and inflammation.