Role of Heme Oxygenase-1 in Polymyxin B-Induced Nephrotoxicity in Rats
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/09/2013
20/09/2013
2012
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Resumo |
Polymyxin B (PMB) is a cationic polypeptide antibiotic with activity against multidrug-resistant Gram-negative bacteria. PMB-induced nephrotoxicity consists of direct toxicity to the renal tubules and the release of reactive oxygen species (ROS) with oxidative damage. This study evaluated the nephroprotective effect of heme oxygenase-1 (HO-1) against PMB-induced nephrotoxicity in rats. Adult male Wistar rats, weighing 286 +/- 12 g, were treated intraperitoneally once a day for 5 days with saline, hemin (HO-1 inducer; 10 mg/kg), zinc protoporphyrin (ZnPP) (HO-1 inhibitor; 50 mu mol/kg, administered before PMB on day 5), PMB (4 mg/kg), PMB plus hemin, and PMB plus ZnPP. Renal function (creatinine clearance, Jaffe method), urinary peroxides (ferrous oxidation of xylenol orange version 2 [FOX-2]), urinary thiobarbituric acid-reactive substances (TBARS), renal tissue thiols, catalase activity, and renal tissue histology were analyzed. The results showed that PMB reduced creatinine clearance (P < 0.05), with an increase in urinary peroxides and TBARS. The PMB toxicity caused a reduction in catalase activity and thiols (P < 0.05). Hemin attenuated PMB nephrotoxicity by increasing the catalase antioxidant activity (P < 0.05). The combination of PMB and ZnPP incremented the fractional interstitial area of renal tissue (P < 0.05), and acute tubular necrosis in the cortex area was also observed. This is the first study demonstrating the protective effect of HO-1 against PMB-induced nephrotoxicity. |
Identificador |
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, WASHINGTON, v. 56, n. 10, pp. 5082-5087, OCT, 2012 0066-4804 http://www.producao.usp.br/handle/BDPI/33538 10.1128/AAC.00925-12 |
Idioma(s) |
eng |
Publicador |
AMER SOC MICROBIOLOGY WASHINGTON |
Relação |
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY |
Direitos |
closedAccess Copyright AMER SOC MICROBIOLOGY |
Palavras-Chave | #ACUTE KIDNEY INJURY #ACUTE-RENAL-FAILURE #GRAM-NEGATIVE BACTERIA #OXIDATIVE STRESS #PROTECTIVE ROLE #TUBULAR CELLS #COLISTIN #EXPRESSION #TOXICITY #ANTIBIOTICS #MICROBIOLOGY #PHARMACOLOGY & PHARMACY |
Tipo |
article original article publishedVersion |