Ethyl acetate extract of (L.) Gaertn. reduces methotrexate-induced renal damage in rats via antioxidant, anti-inflammatory, and antiapoptotic actions.

UNLABELLED

Methotrexate (MTX) is a chemotherapeutic agent and an immunosuppressant used to treat cancer and autoimmune diseases. However, its use is limited by its multi-organ toxicity, including nephrotoxicity, which is related to MTX-driven oxidative stress. Silencing oxidative stressors is therefore an important strategy in minimizing MTX adverse effects.Medicinal plants rich in phenolic compounds are probable candidates to overcome these oxidants. Herein, . ethyl acetate extract showed powerful radical-scavenging potential (IC = 0.0716) comparable to those of the standard natural (ascorbic acid, IC = 0.045) and synthetic (BHA, IC = 0.056) antioxidants. The effect of . ethyl acetate extract against MTX-induced nephrotoxicity in rats was evaluated by administering the extract (400 mg/kg/day) or the standard antioxidant silymarin (100 mg/kg/day) orally for 5 days before and 5 days after a single MTX injection (20 mg/kg, i.p.). showed slight superiorities over silymarin in restoring the MTX-impaired renal functions, with approximately twofold decreases in overall kidney function tests. also improved renal antioxidant capacity and reduced the MTX-induced oxidative stress. Moreover, inhibited MTX-initiated apoptotic and inflammatory cascades, and attenuated MTX-induced histopathological changes in renal tissue architecture.Phytochemical investigation of the extract led to the purification of the phenolics quercitrin (), cinchonains 1a () and 1b (), -clovamide (), -clovamide (), and glochidioboside (); a structurally similar with many of the reported antioxidant and nephroprotective agents. In conclusion, these data demonstrate that exhibits nephroprotective effect against MTX-induced kidney damage via its antioxidant, antiapoptotic and anti-inflammatory mechanisms.

TAXONOMY

Functional Disorder, Traditional Medicine, Herbal Medicine.