Protective Effects of Ascorbic Acid on Gentamicin-induced Nephrotoxicity and Associated Cardiovascular Dysfunctions in Type 1 Diabetic Rats
Temitayo Olabisi Ajibade
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
Anuoluwapo Bolaji-olutunji
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
Oluwatofunmi Endurance Onipede
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
Olaoluwa Isaac Bello *
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
Adewumi Victoria Adeogun
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
Zaccheaus Akinkunmi Olayiwola
Department of Veterinary Pharmacology and Toxicology, University of Ibadan, Oyo State, Nigeria.
Taiwo Olaide Oyagbemi
Federal College of Animal Health and Production Technology, Ibadan, Nigeria.
Temidayo Olutayo Omobowale
Department of Veterinary Medicine, University of Ibadan, Oyo State, Nigeria.
Oluwafemi Omoniyi Oguntibeju
Phytomedicine and Phytochemistry Group, Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Bellville, South Africa.
Momoh Audu Yakubu
Department of Environmental & Interdisciplinary Sciences, College of Science, Engineering & Technology, Vascular Biology Unit, Center for Cardiovascular Diseases, COPHS, Texas Southern University, Houston, TX, USA.
Ademola Adetokunbo Oyagbemi
Department of Veterinary Physiology and Biochemistry, University of Ibadan, Oyo State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Diabetes mellitus is a major risk factor for chronic kidney disease, and the clinical use of effective antibiotics like gentamicin is often limited by its severe nephrotoxicity. This study evaluated the protective effects of ascorbic acid against gentamicin-induced nephrotoxicity and associated cardiovascular dysfunctions in a type 1 diabetic rat model. Twenty-four male Wistar rats were equally divided into four groups (n=6) as follows: Group 1 (control); group 2 (diabetic); group 3 (diabetic plus gentamicin); and Group 4 (diabetic plus gentamicin treated with ascorbic acid). Markers of renal function (urea and creatinine), primary hemodynamic parameters (blood pressure and heart rate), serum nitric oxide (NO), markers of oxidative stress [Malondialdehyde (MDA), hydrogen peroxide (H2O2),] and endogenous antioxidants (GSH, SOD, GPx, GST) were assessed. The heart and kidney tissues were fixed in 10% neutral-buffered formalin for histology and immunohistochemical expressions of cystatin C and angiotensin converting enzyme (ACE) in renal tissues, and cardiac troponin I (cTnI), matrix metalloproteinase-2 (MMP-2) in cardiac tissues. The diabetic plus gentamicin group had significant (p<0.05) elevation in urea, creatinine, MDA, H2O2, blood pressure, and heart rate, but GSH, SOD, GPx, GST and NO decreased significantly(p<0.05), when compared with ascorbic acid treated rats. Histopathological lesions of moderate congestion of the kidney and severe inflammation in the cardiac tissues observed in diabetic plus gentamicin group were absent in ascorbic acid group. The expressions of ACE and cystatin C in renal tissues, and cTnI and MMP-2 in cardiac tissues were lower in ascorbic acid group. In conclusion, ascorbic acid protected against gentamicin-induced nephrotoxicity and cardiovascular dysfunction in diabetic rats; its inclusion in therapeutic regimen for the management of drug-induced organ damage in diabetic patients is therefore recommended.
Keywords: Antioxidant, diabetes, hypertension, rat