Biochemical and histological study of rat liver and kidney injury induced by Cisplatin.

Biochemical and histological study of rat liver and kidney injury induced by Cisplatin.
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DOI:
10.1293/tox.26.293
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发表时间:
2013-09
影响因子:
1.2
通讯作者:
Punsawad C
Punsawad C
中科院分区:
医学4区
文献类型:
--
作者:
Palipoch S;Punsawad C

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顺铂是一种广泛用于治疗多种癌症的化疗药物。它被记录为临床肾毒性和肝毒性的主要原因。本研究的目的是探讨氧化应激在顺铂所致肝肾损伤发病机制中的作用。 Wistar 大鼠被分为四组。第1组(对照)腹腔内(IP)注射单剂量的0.85%生理盐水。第2、3和4组分别以10、25和50mg/kg体重(BW)的单剂量顺铂腹腔注射。注射后24、48、72、96和120小时,评估体重、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿素氮(BUN)、肌酐、丙二醛(MDA)和超氧化物歧化酶(SOD)活性以及肝脏和肾脏的组织学。顺铂导致第 2、3 和 4 组大鼠在所有注射后间隔的体重减少。注射顺铂后血清ALT、AST、BUN以及肾脏和肝脏的肌酐和MDA水平显着升高,尤其是在48和72 h,而SOD活性降低。 50 mg/kg 顺铂时,肝脏切片显示中度至重度充血,伴有肝动脉、门静脉和胆管扩张以及肝索解体。肾脏切片显示在 25 和 50 mg/kg 顺铂下出现轻度至中度肾小管坏死。因此,氧化应激与肝肾损伤导致生化和组织学改变的发病机制有关。
Cisplatin is a chemotherapeutic agent widely used in treatment of several cancers. It is documented as a major cause of clinical nephrotoxicity and hepatotoxicity. The purpose of this study was to investigate the involvement of oxidative stress in the pathogenesis of cisplatin-induced liver and kidney injury. Wistar rats were divided into four groups. Group 1 (control) was intraperitoneally (IP) injected with a single dose of 0.85% normal saline. Groups 2, 3 and 4 were IP injected with single doses of cisplatin at 10, 25 and 50 mg/kg body weight (BW), respectively. At 24, 48, 72, 96 and 120 h after injection, BW, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), and activity of superoxide dismutase (SOD) and histology of the liver and kidney were evaluated. Cisplatin caused a reduction in BW of rats in groups 2, 3 and 4 at all post injection intervals. The levels of serum ALT, AST, BUN and creatinine and MDA of the kidney and liver were markedly increased especially at 48 and 72 h, whereas the activity of SOD was decreased after cisplatin injection. Liver sections revealed moderate to severe congestion with dilation of the hepatic artery, portal vein and bile duct and disorganization of hepatic cords at 50 mg/kg of cisplatin. Kidney sections illustrated mild to moderate tubular necrosis at 25 and 50 mg/kg of cisplatin. Therefore, oxidative stress was implicated in the pathogenesis of liver and kidney injury causing biochemical and histological alterations.
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