title: Protective effect of captopril, olmesartan, melatonin and compound 21 on doxorubicin-induced nephrotoxicity in rats.
abstract: Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity.
authors: Department of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovak Republic. fedor.simko@fmed.uniba.sk.
authors: J
authors: J
authors: Hrenák
authors: K
authors: K
authors: Arendášová
authors: R
authors: R
authors: Rajkovičová
authors: S
authors: S
authors: Aziriová
authors: K
authors: K
authors: Repová
authors: K
authors: K
authors: Krajčírovičová
authors: P
authors: P
authors: Celec
authors: N
authors: N
authors: Kamodyová
authors: A
authors: A
authors: Bárta
authors: M
authors: M
authors: Adamcová
authors: L
authors: L
authors: Paulis
authors: F
authors: F
authors: Simko
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D002216:Captopril / Q000627:therapeutic use*; D004317:Doxorubicin; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists*; D012076:Renal Agents / Q000627:therapeutic use; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D007093:Imidazoles; D017382:Reactive Oxygen Species; D044139:Receptor, Angiotensin, Type 2; D012076:Renal Agents; D013777:Tetrazoles; D004317:Doxorubicin; C437965:olmesartan; D002216:Captopril; D008550:Melatonin