Influence of Oxidative stress and NF‐κβ/CRP/Bcl‐2 Signaling on Gentamicin Induced Renal Toxicology and the ameliorative effect of chloroform extract of Abrus precatorius in male Wistar rats

Abstract

The kidneys play an important role in attenuating the toxicity of various drugs and chemicals. Gentamicin, a widely used effective aminoglycoside is one of such drugs, however, dose and time‐dependent nephrotoxicity limits its clinical use. This study evaluates the influence of oxidative stress, and inflammatory transcription factors in the pathogenesis of Gentamicin induced‐renal damage and the ameliorative potential of chloroform stem extract of Abrus precatorius. Twenty‐four male Wistar rats were divided into five equal groups. Group I was the negative control group while II was the positive control group which received gentamicin 100 mg/kg intra‐peritoneally daily for 6 days. Groups III and IV were pretreated with 100 and 200 mg/kg extract, respectively, for the first 3 days and then concurrently with gentamicin 100 mg/kg for 6 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analyses. Results revealed no significant hematological changes across the groups, Gentamicin caused significant increases in serum creatinine, urea, xanthine oxidase, nitric oxide, and myeloperoxidase levels. Gentamicin toxicity also resulted in increases in levels of renal advanced oxidative protein products, protein carbonyl, hydrogen peroxide, malondialdehyde levels. Furthermore, depletion in the activity of superoxide dismutase, glutathione S‐transferase, and contents of reduced glutathione, protein thiol, and non‐protein thiol. Gentamicin also caused focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy in the kidney tissue. Levels of expressions of inflammatory mediators such as CRP and NF‐κβ levels were increased, alongside a decrease in Bcl‐2, an anti‐apoptotic protein. Gentamicin induces renal damage through the generation of oxidative stress, up‐regulation of pro‐inflammatory cytokines and down regulation of anti‐apoptotic protein. These were ameliorated with chloroform stem extract of Abrus precatorius.