title: Mitochondrial dysfunction and electron transport chain complex defect in a rat model of tenofovir disoproxil fumarate nephrotoxicity.
abstract: The long-term use of tenofovir, a commonly used anti-HIV drug, can result in renal damage. The mechanism of tenofovir disoproxil fumarate (TDF) nephrotoxicity is not clear, although it has been shown to target proximal tubular mitochondria. In the present study, the effects of chronic TDF treatment on the proximal tubular function, renal mitochondrial function, and the activities of the electron transport chain (ETC) complexes were studied in rats. Damage to proximal tubular mitochondria and proximal tubular dysfunction was observed. The impaired mitochondrial function such as the respiratory control ratio, 2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide (MTT) reduction, and mitochondrial swelling was observed. The activities of the electron chain complexes I, II, IV, and V were decreased by 46%, 20%, 26%, and 21%, respectively, in the TDF-treated rat kidneys. It is suggested that TDF induced proximal tubular mitochondrial dysfunction and ETC defects may impair ATP production, resulting in proximal tubular damage and dysfunction.
authors.affiliation: Departments of Biochemistry, Christian Medical College, Bagayam, Vellore, 632 002, India.
authors.forename: Hemalatha
authors.initials: H
authors.lastname: Ramamoorthy
authors.forename: Premila
authors.initials: P
authors.lastname: Abraham
authors.forename: Bina
authors.initials: B
authors.lastname: Isaac
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D019380:Anti-HIV Agents / Q000633:toxicity*; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005198:Fanconi Syndrome / Q000139:chemically induced / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D063065:Organophosphonates / Q000633:toxicity*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism; D017208:Rats, Wistar; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D045222:Electron Transport Chain Complex Proteins; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine
keywords: Electron Chain Complexes; Mitochondrial Dysfunction; Mitochondrial Injury; Proximal Tubular Damage; Tenofovir Disoproxil Fumarate