Reno-protective effect of agmatine in methotrexate-induced kidney injury in rats

Background: L-arginine's endogenous metabolite agmatine (AGM) is recognized to have anti-inflammatory, anti-apoptotic, and antioxidant qualities. Investigating the dose-dependent renal-protective effect of AGM in rats with MTX-induced kidney damage was the goal of this study. Methods: In this experimental study, fifty male rats were divided into five groups (n = 10). Group I (control) received oral saline for 7 days and IP saline on day 7. Group II (MTX) received oral saline for 7 days and IP MTX (20 mg/kg) on day 7. Groups III–V received AGM orally at 10, 20, and 40 mg/kg/day for 7 days, followed by IP MTX (20 mg/kg) on day 7. Results: Intraperitoneal MTX (20 mg/kg) significantly increased renal somatic index, MDA, 8-OHdG, NO, TNF-α, IL-1, serum creatinine, BUN, and NF-κB, while it decreased GSH, SOD, HO-1 activity, Nrf2 expression, and creatinine clearance. AGM administration at various doses showed a protective renal effect against MTX-induced changes. Conclusions: Many disorders can be effectively treated with MTX. The toxicity of MTX, which includes nephrotoxicity with a mechanism involving inflammation and oxidative damage, frequently limits its therapeutic uses.