Activation of renal haeme oxygenase-1 alleviates gentamicin-induced acute nephrotoxicity in rats

This study aimed to investigate whether activation of haeme oxygenase (HO)-1 enzyme by haemin would have beneficial effects on the functional and histological outcome against gentamicin-induced renal damage in rats and sought to elucidate the underlying mechanisms of the therapeutic action.

Nephrotoxicity was induced by injection of gentamicin (80 mg/kg, i.p.) once daily for seven days. Haemin (50 μmol/kg, i.p.) was given to the control and gentamicin-treated rats in the presence or absence of a HO-1 inhibitor, zinc protoporphyrin IX (ZnPP, 50 μmol/kg per day, i.p.).

Haemin treatment prevented gentamicin-induced elevated serum creatinine, urinary protein levels and ameliorated the impaired creatinine clearance. Haemin compensated the deficits in antioxidant enzyme activity and attenuated lipid peroxidation along with decreased reactive oxygen species (ROS) production in renal tissues due to gentamicin. Moreover, haemin pre-administration evoked increased renal HO-1 activity. Additionally, haemin significantly attenuated elevated renal tumour necrosis factor-α (TNF-α), nuclear factor-kappaB (NF-κB) levels and caspase-3 activity alongside ameliorating glomerular pathology. These therapeutic effects were abolished by ZnPP pretreatment.

Here is the first evidence demonstrating the protective effect of HO-1 against gentamicin-associated nephrotoxicity. Suppression of oxidative/inflammatory insults alongside the corresponding decline of apoptosis were presumably responsible for this renoprotection.