Protective mechanisms of icariin in methotrexate-induced renal damage: role of Nrf2/HO-1 and apoptosis reduction.

Objectives: Thus, the study was designed to assess the ability of ICA to ameliorate MTX-induced renal toxicity in rats and determine the pathogenetic pathways of oxidative stress, inflammation, and apoptosis.

Methods: Mtx renal toxicity was developed following an intraperitoneal administration of 20 mg/kg MTX. ICA was orally given at 100 mg/kg/day for two consecutive weeks. Experimental indicators included: biochemical renal function - BUN, SCr; and oxidative stress - SOD, GSH-Px, MDA. Other histological studies included immunohistochemical staining for Nrf2 and HO-1, QPCR of pro-inflammatory cytokines and biomarker of kidney injury, and TUNEL assay to assess the protective effects affiliated with ICA.

Results: In an animal model treated with MTX, renal damage was reflected by increased oxidative stress, inflammatory-borne cytokines, and apoptotic indices. ICA treatment ameliorated these effects to a great extent by reversing changes in antioxidant enzyme activities, suppressing lipid peroxidation and regulating the Nrf2/HO-1 pathway. This was evidenced by the decrease in pro-inflammatory and kidney injury genes in the ICA-treated groups but by significant histological ameliorations of kidney structure. TUNEL assay proved the decreased apoptotic index in kidney tissue.

Conclusions: These findings exhibited the therapeutic efficacy of ICA for attenuating renal injury from MTX and established that it mainly exerts its cytoprotective effects through the Nrf2/HO-1 pathway.