title: Vitamin D deficiency aggravates nephrotoxicity, hypertension and dyslipidemia caused by tenofovir: role of oxidative stress and renin-angiotensin system.
abstract: Vitamin D deficiency (VDD) is prevalent among HIV-infected individuals. Vitamin D has been associated with renal and cardiovascular diseases because of its effects on oxidative stress, lipid metabolism and renin-angiotensin-aldosterone system (RAAS). Tenofovir disoproxil fumarate (TDF), a widely used component of antiretroviral regimens for HIV treatment, can induce renal injury. The aim of this study was to investigate the effects of VDD on TDF-induced nephrotoxicity. Wistar rats were divided into four groups: control, receiving a standard diet for 60 days; VDD, receiving a vitamin D-free diet for 60 days; TDF, receiving a standard diet for 60 days with the addition of TDF (50 mg/kg food) for the last 30 days; and VDD+TDF receiving a vitamin D-free diet for 60 days with the addition of TDF for the last 30 days. TDF led to impaired renal function, hyperphosphaturia, hypophosphatemia, hypertension and increased renal vascular resistance due to downregulation of the sodium-phosphorus cotransporter and upregulation of angiotensin II and AT1 receptor. TDF also increased oxidative stress, as evidenced by higher TBARS and lower GSH levels, and induced dyslipidemia. Association of TDF and VDD aggravated renovascular effects and TDF-induced nephrotoxicity due to changes in the redox state and involvement of RAAS.
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Daniele
authors.initials: D
authors.lastname: Canale
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Bragança
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Janaína Garcia
authors.initials: JG
authors.lastname: Gonçalves
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Maria Heloisa Massola
authors.initials: MH
authors.lastname: Shimizu
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Talita Rojas
authors.initials: TR
authors.lastname: Sanches
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Lúcia
authors.initials: L
authors.lastname: Andrade
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Rildo Aparecido
authors.initials: RA
authors.lastname: Volpini
authors.affiliation: Nephrology Department, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Seguro
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents; D050171:Dyslipidemias / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism; D000068698:Tenofovir; D015854:Up-Regulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014808:Vitamin D Deficiency / Q000150:complications* / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D011945:Receptors, Angiotensin; D050608:Sodium-Phosphate Cotransporter Proteins; D000068698:Tenofovir