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 maleWistar 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.

Expression profiles of genes related to melatonin and oxidative stress in human renal proximal tubule cells treated with antibiotic amphotericin B and its modified forms

“…Previous research showed that use of melatonin significantly reduces drug-induced nephrotoxicity caused by oxidative stress. Such a mechanism was described for amikacin (Parlakpinar et al, 2003), vancomycin (Celik et al, 2005), gentamicin (Ozbek et al, 2005), methotrexate (Abraham et al, 2010), AmB (Lin and Chuang, 2010), and doxorubicin (Hrenák et al, 2013). At physiological concentrations (1 to 100 mM) melatonin affected the expression of genes involved in oxidative stress in cells treated with AmB (Lin and Chuang, 2010).…”

Amelioration of CCl4-Induced Hepatotoxicity in Rabbits byLepidium sativumSeeds

“…Rabbits were purchased from the animal house of King Fahd Medical Research Centre (KFMRC), King Abdulaziz University, KSA. Rabbits were maintained for Care and Use of Laboratory Animals according to the criteria of US National Institutes of Health (NIH Publication No 8523, revised 1985) [ 17 ].…”

Pi̇yelonefri̇t Hasarina Bağli Geli̇şen Böbrek Skarinin Önlenmesi̇nde Kaptopri̇l Ve Ketoti̇feni̇n Etki̇si̇

“…Intraperitoneal cefotaxime was given for 5 days at the dose of 200 mg/kg once a day, starting 72 hours after surgery. Captopril dose in rats ranged from 10 to 100 mg in similar studies and the dose of 50 mg/kg/day was used in this study (15)(16)(17). Ketotifen was used in the dose of 1 mg/kg/day by orogastric lavage (18,19).…”