Yagmurca Murat, Erdogan Hasan, Iraz Mustafa, Songur Ahmet, Ucar Muharrem, Fadillioglu Ersin
Department of Histology and Embryology, Faculty of Medicine, Afyon Kocatepe University, Afyon, Turkey.
Clin Chim Acta. 2004 Oct;348(1-2):27-34. doi: 10.1016/j.cccn.2004.03.035.
Nephrotoxicity is one of the important side effects of antracycline antibiotics. The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, against nephrotoxicity induced by doxorubicin (DXR).
The rats were divided into control, CAPE alone, doxorubicin (20 mg/kg, i.p.) and doxorubicin plus CAPE (10 micromol/kg/day, i.p.) groups. At the end of the 10th day, kidney tissues were removed for light microscopy and analysis. The levels of tissues protein carbonyl content (PC), malondialdehyde (MDA) and nitric oxide (NO) as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and myeloperoxidase (MPO) were determined. Plasma oxidants and antioxidants were also measured.
The activities of CAT and GSH-Px were decreased as well as myeloperoxidase, NO, MDA and PC were increased in renal tissue of doxorubicin group compared with the other groups. Plasma GSH-Px activity was higher in doxorubicin plus CAPE group than the others and plasma MDA level was higher in doxorubicin group than the other groups. There were glomerular vacuolization, tubular desquamation, loss of brush border, and adhesion to Bowman's in the light microscopy in the kidneys of doxorubicin group. The tubules and brush border were almost normal and some of the glomerulus was filled with fine vacuoles in CAPE treated rats.
Doxorubicin caused renal injury and CAPE treatment prevented lipid peroxidation and protein oxidation in renal tissue and partially preserved glomerulus and tubules.
肾毒性是蒽环类抗生素的重要副作用之一。本研究旨在探讨抗氧化剂咖啡酸苯乙酯(CAPE)对阿霉素(DXR)诱导的肾毒性的影响。
将大鼠分为对照组、单独使用CAPE组、阿霉素组(20mg/kg,腹腔注射)和阿霉素加CAPE组(10μmol/kg/天,腹腔注射)。在第10天结束时,取出肾脏组织进行光学显微镜检查和分析。测定组织蛋白羰基含量(PC)、丙二醛(MDA)和一氧化氮(NO)水平以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和髓过氧化物酶(MPO)的活性。还测量了血浆氧化剂和抗氧化剂。
与其他组相比,阿霉素组肾组织中CAT和GSH-Px活性降低,髓过氧化物酶、NO、MDA和PC升高。阿霉素加CAPE组血浆GSH-Px活性高于其他组,阿霉素组血浆MDA水平高于其他组。阿霉素组肾脏光学显微镜检查显示有肾小球空泡化、肾小管脱落、刷状缘丧失以及与鲍曼囊粘连。在CAPE处理的大鼠中,肾小管和刷状缘几乎正常,一些肾小球充满细小空泡。
阿霉素导致肾损伤,CAPE治疗可预防肾组织中的脂质过氧化和蛋白质氧化,并部分保留肾小球和肾小管。