Evaluation of the Renoprotective Effects of Valsartan in Methotrexate-Induced Acute Kidney Injury in Rats

Abstract

Methotrexate (MTX) is a widely used chemotherapeutic agent known for its nephrotoxic effects, which can lead to acute kidney injury in hospitalized patients. However, the mechanism by which MTX induces nephrotoxicity is not entirely clear, but it is believed to involve oxidative stress and direct toxic effects on renal tubules. Valsartan, an angiotensin II receptor blocker, has been shown to exert renoprotective effects in various contexts, including diabetic nephropathy. In this study, the renoprotective potential of Valsartan to mitigate MTX-induced acute kidney in rats was explored. A total of twenty-four Wistar rats were randomly assigned to three groups. The Control Group (GRP 1) was administered an oral dose of 1 ml/kg of normal saline. The second group (GRP 2) received a single Intraperitoneal (IP) dose of 20 mg/kg MTX for a duration of 5 consecutive days. The third Group (GRP 3) was subjected to a single IP dose of 20 mg/kg MTX followed by an oral dose of 30 mg/kg Valsartan (Val) over the same 5-day period. At the end of the experiment, the levels of serum biochemical parameters, renal damage markers, and inflammatory and oxidative stress markers were accessed. Additionally, the impact of MTX on kidney tissue histology was investigated. The results indicate that MTX administration in rats led to a significant increase in serum biochemical parameters, renal damage markers, inflammatory markers, and oxidative stress markers, as well as changes in kidney histology. However, the administration of Val following MTX treatment to rats attenuated these effects. Conclusions: Val shows therapeutic potential in the treatment of MTX-induced kidney injury and its associated consequences.