Evaluation of the therapeutic effects of Nebivolol on TDF-induced nephrotoxicity in rats

Abstract

Acquired Immunodeficiency Syndrome (AIDS) continues to be a global public health issue. Tenofovir Disoproxil Fumarate (TDF) was the first available nucleotidic reverse transcription inhibitor and it is a widely prescribed antiretroviral medication for treatment of Human Immunodeficiency Virus (HIV). However, the long-term use of TDF has been associated with a number of toxicities, including those affecting the kidney. Nebivolol (NBV) is a third generation ²1-adrenergic receptor antagonist that has been available for the treatment of hypertension and heart diseases based on the findings that NBV may protect renal structure and function through its vasodilatory and antioxidant properties. In view of the high worldwide antirretroviral therapy with TDF among HIV-infected individuals, the current study establishes that NBV could be an effective therapeutic option for attenuating TDF-induced nephrotoxicity. Wistar rats will be divided into four groups: Control, receiving a standard diet for 30 days; TDF, receiving a standard diet with TDF (300 mg/kg food) for 30 days; NBV, receiving a standard diet for 30 days with NBV (100 mg/kg food) in the last 15 days; and TDF+NBV receiving a standard diet with TDF for 30 days and NBV in the last 15 days. At the end of the protocol, animals will be euthanized. Blood, urine and tissue samples will be collected. We will determine inulin clearance, mean arterial pressure and renal blood flow. Biochemical assays will be applied to evaluate biochemical profile (electrolytes, oxidative stress, metabolic syndrome, endotelial dysfunction). In addition, we will perform histomorphometrics and immunohistochemical studies as a means to evaluate kidney structure and inflammatory pathways. (AU)