Protective role of Boerhavia diffusa root extract in methotrexate-induced renal injury: evidence from oxidative stress, molecular, and immunohistochemical markers

Methotrexate (MTX), a chemotherapeutic and immunosuppressive drug, induces nephrotoxicity via oxidative stress, inflammation, and apoptosis. The current study aims to evaluate the nephroprotective potential of Boerhavia diffusa root extract (BRE) in a rat model of MTX-induced nephrotoxicity. Nephrotoxicity was induced in rats with a single MTX dose (7 mg/kg, i.p.). Boerhavia diffusa root extract (BRE) was administered orally (100, 200, 400 mg/kg) for 7 days. Renal function (Urea, Blood Urea Nitrogen- BUN and Creatinine), oxidative stress markers- reduced Glutathione(GSH), total antioxidant capacity (TAC) and injury markers- kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) were evaluated. Tumor necrosis factor-alpha (TNF-α) and Interleukin-1alpha(IL-1α)expression was assessed immunohistochemically and c-Jun N-terminal Kinase 1mRNA ( JNK1) expression by Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). MTX impaired renal function, increased oxidative stress, and upregulated inflammatory markers. BRE improved renal markers, reduced KIM-1 and NGAL levels, suppressed TNF-α, IL-1α, and JNK1 expression, with maximal effect at 400 mg/kg in a dose dependent manner. BRE provides significant nephroprotection against MTX-induced renal injury, likely via antioxidant, anti-inflammatory mechanisms as evidenced from the results this study.