title: Depletion of the cellular antioxidant system contributes to tenofovir disoproxil fumarate - induced mitochondrial damage and increased oxido-nitrosative stress in the kidney.
abstract: BACKGROUND
  Nephrotoxicity is a dose limiting side effect of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of HIV infection. The mechanism of tenofovir nephrotoxicity is not clear. Tenofovir is specifically toxic to the proximal convoluted tubules and proximal tubular mitochondria are the targets of tenofovir cytotoxicity. Damaged mitochondria are major sources of reactive oxygen species and cellular damage is reported to occur after the antioxidants are depleted. The purpose of the study is to investigate the alterations in cellular antioxidant system in tenofovir induced renal damage using a rat model.
  
  
  RESULTS
  Chronic tenofovir administration to adult Wistar rats resulted in proximal tubular damage (as evidenced by light microscopy), proximal tubular dysfunction (as shown by Fanconi syndrome and tubular proteinuria), and extensive proximal tubular mitochondrial injury (as revealed by electron microscopy). A 50% increase in protein carbonyl content was observed in the kidneys of TDF treated rats as compared with the control. Reduced glutathione was decreased by 50%. The activity of superoxide dismutase was decreased by 57%, glutathione peroxidase by 45%, and glutathione reductase by 150% as compared with control. Carbonic Anhydrase activity was decreased by 45% in the TDF treated rat kidneys as compared with control. Succinate dehydrogenase activity, an indicator of mitochondrial activity was decreased by 29% in the TDF treated rat kidneys as compared with controls, suggesting mitochondrial dysfunction.
  
  
  CONCLUSIONS
  Tenofovir- induced mitochondrial damage and increased oxidative stress in the rat kidneys may be due to depletion of the antioxidant system particularly, the glutathione dependent system and MnSOD.
authors: Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu, India. premilaabraham@cmcvellore.ac.in
authors: Premila
authors: P
authors: Abraham
authors: Hemalatha
authors: H
authors: Ramamoorthy
authors: Bina
authors: B
authors: Isaac
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D063065:Organophosphonates / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D000068698:Tenofovir; D000099156:Superoxide Dismutase 2
chemical_list: D000225:Adenine; D000975:Antioxidants; D005978:Glutathione; D005979:Glutathione Peroxidase; D063065:Organophosphonates; D013482:Superoxide Dismutase; D000068698:Tenofovir; D000099156:Superoxide Dismutase 2
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