Protective effect of selected calcium channel blockers and prednisolone, a phospholipase-A2 inhibitor, against gentamicin and carbon tetrachloride-induced nephrotoxicity.
The ameliorative effect of calcium channel blockers (CCBs) and a phospholipase-A2 inhibitor in drug-/chemical-induced nephrotoxicity was investigated. Rats were divided into 7 groups of 5 rats in each group. In the gentamicin model, group I rats were pretreated with normal saline (10 ml kg(-1)), while groups II-VII rats were pretreated with normal saline (10 ml kg(-1)), ascorbic acid (10 mg kg(-1)), nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)), respectively, perorally 1 h before intraperitoneal (i.p.) injection of gentamicin (40 mg kg(-1)) for 14 days. In the carbon tetrachloride (CCl4) model, rats were pretreated with CCBs and prednisolone for 7 days before inducing nephrotoxicity with 20% CCl4 (1.5 ml kg(-1)). Rats were thereafter killed and blood and tissue samples were collected for assessments. I.p. injections of gentamicin and CCl4 caused significant hypernatremia, hypokalemia, hypocalcemia, hypophosphatemia, and hyperchloremic alkalosis and reduced renal tissue levels of antioxidants. Also, significant reductions in the hemoglobin, packed cell volume, red blood cells, and platelet indices were observed. Pretreatments with nifedipine (0.86 mg kg(-1)), verapamil (4.3 mg kg(-1)), diltiazem (3.43 mg kg(-1)), and prednisolone (0.57 mg kg(-1)) significantly ameliorated the deleterious effects of gentamicin and CCl4 possibly via antioxidant and anti-lipoperoxidation mechanisms. The results obtained in this study suggest potential clinical usefulness of tested CCBs and prednisolone in drug-/chemical-induced nephrotoxicity.
Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria aj_akindele@yahoo.com ajakindele@cmul.edu.ng.
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Akindele
Department of Pharmacology, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria.
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Adeneye
Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.
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Olatoye
Department of Pathology and Forensic Medicine, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria.
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Benebo
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D019610:Cytoprotection; D004110:Diltiazem / Q000494:pharmacology; D004195:Disease Models, Animal; D005839:Gentamicins; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology*; D011239:Prednisolone / Q000494:pharmacology*; D017208:Rats, Wistar; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D000975:Antioxidants; D015415:Biomarkers; D002121:Calcium Channel Blockers; D005839:Gentamicins; D064801:Phospholipase A2 Inhibitors; D011239:Prednisolone; D014700:Verapamil; D002251:Carbon Tetrachloride; D004110:Diltiazem; D009543:Nifedipine
Nephroprotective; calcium channel blockers; phospholipase-A2 inhibitor; renal toxicity