顺铂诱导大鼠肝和肾损伤的生化及组织学研究
Biochemical and histological study of rat liver and kidney injury induced by Cisplatin.
作者信息
Palipoch Sarawoot, Punsawad Chuchard
机构信息
School of Medicine, Walailak University, Nakhon Si Thammarat 80161, Thailand.
出版信息
J Toxicol Pathol. 2013 Sep;26(3):293-9. doi: 10.1293/tox.26.293. Epub 2013 Oct 15.
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.
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。本研究的目的是调查氧化应激在顺铂诱导的肝肾损伤发病机制中的作用。将Wistar大鼠分为四组。第1组(对照组)腹腔注射单剂量0.85%的生理盐水。第2、3和4组分别腹腔注射单剂量10、25和50mg/kg体重的顺铂。在注射后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)水平、超氧化物歧化酶(SOD)活性以及肝肾组织学。顺铂导致第2、3和4组大鼠在所有注射后时间点体重下降。血清ALT、AST、BUN和肌酐水平以及肝肾MDA水平显著升高,尤其是在48和72小时,而顺铂注射后SOD活性降低。肝脏切片显示,在50mg/kg顺铂剂量下,肝脏有中度至重度充血,肝动脉、门静脉和胆管扩张,肝索紊乱。肾脏切片显示,在25和50mg/kg顺铂剂量下,有轻度至中度肾小管坏死。因此,氧化应激与肝肾损伤的发病机制有关,导致生化和组织学改变。