Mangiferin ameliorates methotrexate-induced nephrotoxicity via suppression of oxidative inflammation, caspase apoptosis and genotoxicity in rats.

OBJECTIVE

Methotrexate (MTX) is an efficacious antimetabolite drug used in the treatment of several cancers. However, MTX downside is its side effect toxicities that affect delicate organs, including the kidney. Therefore, this study evaluated whether mangiferin (MGF), a xanthone glycoside, could exert protection against MTX-induced nephrotoxicity in male Wistar rats.

MATERIALS AND

METHODS

Rats were randomly divided into 4 groups. Control group was given normal saline; MGF group was given MGF (20 mg/kg body weight orally) for 10 days; MTX group (20 mg/kg body weight intraperitoneally) received a dose of MTX on day 7. Serum urea, creatinine and uric acid were measured. Renal antioxidant enzymes (SOD, CAT and GPx), cytokines (IL-4, IL-10, IL-6, and TNF-α) and apoptosis caspases levels were determined by ELISA method followed by genotoxic and histological assessments.

RESULTS

MTX induced marked renal dysfunction demonstrated by elevated urea, creatinine and uric acid levels compared to the control. The renal cytokines, caspase 3 and 9 were significantly increased followed by DNA breaks and histopathological lesions. Interestingly, MGF administration prominently reversed the renal dysfunction and ameliorated the renal adverse biochemical alterations in comparison to the MTX group. The DNA breaks level was reduced and the histopathological lesions were alleviated.

CONCLUSION

These findings suggest that MGF is a promising natural agent for combating MTX-induced nephrotoxicity.