Exogenous glutathione protects against gentamicin-induced acute kidney injury by inhibiting NF-κB pathway, oxidative stress, and apoptosis and regulating PCNA

Abstract

This study was designed, for the first time, to examine the possible nephroprotective effects of exogenous glutathione (EGSH) (100 mg/kg, intraperitoneally) on gentamicin-induced acute kidney injury (GM-induced AKI). EGSH reduced renal histopathological changes, inflammatory cell infiltration, and improved renal dysfunction in rats with AKI. EGSH ameliorated GM-induced renal oxidative stress by promoting the renal activities of catalase, glutathione peroxidase, and superoxide dismutase and diminishing renal malondialdehyde and serum nitric oxide levels. Interestingly, EGSH inhibited intrinsic apoptosis by downregulating Bax and caspase-3 and upregulating Bcl2 in the kidney of rats with AKI. EGSH decreased GM-induced inflammatory response as reflected by a remarkable decrease in the protein expressions of NF-κB-p65, IL-6, TNF-α, and iNOS and a considerable diminish in myeloperoxidase activity. Finally, EGSH markedly declined proliferative cell nuclear antigen (PCNA) protein expression in the animals with AKI. In summary, EGSH alleviated AKI in rats intoxicated with GM, partially by inhibiting oxidative stress, NF-κB pathway, and intrinsic apoptosis and regulating PCNA.