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

Grant number: 19/20840-0
Support Opportunities:Regular Research Grants
Start date: July 01, 2020
End date: September 30, 2022
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Daniele Canale Cavicchioli
Grantee:Daniele Canale Cavicchioli
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Ana Carolina de Bragança Viciana ; Antonio Carlos Seguro ; Maria Heloisa Massola Shimizu ; Rildo Aparecido Volpini

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)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BERNARDO, DESIREE RITA DENELLE; CANALE, DANIELE; NASCIMENTO, MARIANA MOURA; SHIMIZU, MARIA HELOISA MASSOLA; SEGURO, ANTONIO CARLOS; DE BRAGANCA, ANA CAROLINA; VOLPINI, RILDO APARECIDO. The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury. FRONTIERS IN NUTRITION, v. 9, p. 22-pg., . (18/12297-1, 19/20840-0, 18/04930-6)
NASCIMENTO, MARIANA MOURA; BERNARDO, DESIREE RITA DENELLE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; CANALE, DANIELE. Treatment with beta-blocker nebivolol ameliorates oxidative stress and endothelial dysfunction in tenofovir-induced nephrotoxicity in rats. FRONTIERS IN MEDICINE, v. 9, p. 15-pg., . (18/04930-6, 18/12297-1, 19/20840-0)
BERNARDO, DESIREE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; NASCIMENTO, MARIANA MOURA; CANALE, DANIELE; VOLPINI, RILDO APARECIDO. OBESITY ASSOCIATED WITH VITAMIN D DEFICIENCY IMPAIRS RENAL FUNCTION, HAEMODYNAMICS, METABOLIC PARAMETERS AND AGGRAVATES THE RENAL MORPHOLOGICAL DAMAGE IN RATS SUBMITTED TO ISCHAEMIA-REPERFUSION INJURY. Nephrology Dialysis Transplantation, v. 37, p. 2-pg., . (19/20840-0, 18/12297-1, 18/04930-6)
NASCIMENTO, MARIANA MOURA; BERNARDO, DESIREE; DE BRAGANCA, ANA CAROLINA; MASSOLA SHIMIZU, MARIA HELOISA; SEGURO, ANTONIO CARLOS; VOLPINI, RILDO APARECIDO; CANALE, DANIELE. TREATMENT WITH NEBIVOLOL AMELIORATES RENOVASCULAR ALTERATIONS AND OXIDATIVE STRESS IN TENOFOVIR-INDUCED NEPHROTOXICITY IN RATS. Nephrology Dialysis Transplantation, v. 37, p. 2-pg., . (19/20840-0, 18/12297-1, 18/04930-6)