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.

Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats: Involvement of the INSIG/SREBP pathway

“…We found that antipsychotic-related lipid dysregulation was most apparent in VDD rats, and abolished when drugs were administered in combination with VD supplementation, indicating an increased vulnerability to drug-induced lipid disturbances in the context of VD deficiency. Similarly, a recent study reported that VD deficiency exacerbates tenofovirinduced elevation of serum levels of TC and TG in rats (Canale et al, 2014). Moreover, it has been reported that VD deficiency in obese rats exacerbated nonalcoholic fatty liver disease and increased serum TG level (Roth et al, 2012), whereas VD supplementation successfully protected against high-fat diet-induced obesity and hepatic steatosis, which paralleled with improvement of glucose homeostasis and serum lipid profile (Marcotorchino et al, 2014;Yin et al, 2012).…”

Vitamin D and Infectious Diseases: Simple Bystander or Contributing Factor?

“…Moreover, chronic use of TDF may also lead to a decreased glomerular filtration rate [ 89 ]. An experimental study from our laboratory using a rat model demonstrated that VDD aggravated TDF nephrotoxicity and induced hypertension and hyperlipidaemia [ 90 ].…”

Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

“…NRTI such as tenofovir may target mitochondrial DNA polymerase c and induce oxidative stress, 38,39 and oxidative stress can lead to cellular iron overload. 40 While mitochondrial toxicity is less associated with darunavir, various protease inhibitors were shown to inhibit mitochondrial proteases and cause oxidative stress.…”