Oxidative stress, decreased activities of anti-oxidant enzymes, and neutrophil infiltration contribute to Tenofovir disoproxil fumarate induced renal damage in rats

Abstract

Hemalatha Ramamoorthy, Premila Abraham, Bina Isaac

The mechanism by which tenofovir (TDF) causes renal damage is not clear. To examine the role of oxidative stress in TDF induced renal damage. Rats were administered by gavage 600mg /kg body weight Tenofovir disoproxil fumarate for 35 days. The kidneys were used for light microscopy and lectron microscopy as well as for the assay of markers of oxidative stress and activities of antioxidant enzymes and myeloperoxidase activity, a marker of neutrophil infiltration. TDF administration to the rats resulted in glomerular and tubular damage. Electron microscopically, mitochondrial swelling, disruption of cristae and accumulation of amorphous deposits in the matrix were observed. Significant increase in protein carbonyl content, decrease in reduced glutathione and protein thiol, decrease in the activities of the antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione S transferase and glutathione reductase and a massive increase in myeloperoxidase activity was observed in the kidneys of TDF treated rats. Oxidative stress contributes to TDF induced renal damage in rats. The source of reactive oxygen species may be the damaged mitochondria and or activated neutrophils.

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