英夫利昔单抗调节顺铂诱导的大鼠肝毒性。
Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats.
作者信息
Cüre Medine Cumhur, Cüre Erkan, Kalkan Yıldıray, Kırbaş Aynur, Tümkaya Levent, Yılmaz Arif, Türkyılmaz Ayşegül Küçükali, Şehitoğlu İbrahim, Yüce Süleyman
机构信息
Department of Biochemistry, Recep Tayyip Erdoğan University School of Medicine, Rize, Turkey.
Department of Internal Medicine, Recep Tayyip Erdoğan University School of Medicine, Rize, Turkey.
出版信息
Balkan Med J. 2016 Sep;33(5):504-511. doi: 10.5152/balkanmedj.2016.150576. Epub 2016 Sep 1.
BACKGROUND
Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels.
AIMS
We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis.
STUDY DESIGN
Animal experimentation.
METHODS
Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection.
RESULTS
TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups.
CONCLUSION
Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA-II enzyme levels.
背景
顺铂（Cis）是最常用的抗肿瘤药物之一。它被用作多种实体器官恶性肿瘤的化疗药物，如脑癌、头颈癌、男性和女性泌尿生殖系统癌、膀胱癌和肺癌。英夫利昔单抗可阻断肿瘤坏死因子α（TNF-α）。多项研究报告称，英夫利昔单抗可通过降低细胞因子水平改善细胞损伤。
目的
我们旨在研究英夫利昔单抗对顺铂诱导的肝毒性是否具有预防作用，以及它与顺铂联合使用时是否具有协同作用。
研究设计
动物实验。
方法
将雄性Wistar白化大鼠分为三组：顺铂组、英夫利昔单抗+顺铂（CIN）组和对照组。每组包括10只动物。顺铂组动物接受腹腔单剂量注射顺铂（7mg/kg）。在CIN组中，在注射顺铂前72小时给予单剂量英夫利昔单抗（7mg/kg）。72小时后，给予单剂量顺铂（7mg/kg）。在注射顺铂五天后处死所有大鼠。
结果
顺铂组的TNF-α水平（345.5±40.0pg/mg蛋白）显著高于对照组（278.7±62.1pg/mg蛋白，p=0.003）和CIN组（239.0±64.2pg/mg蛋白，p=0.013）。发现顺铂组碳酸酐酶（CA）-II水平高，而氨基甲酰磷酸合成酶-1（CPS-1）水平低。与顺铂组相比，CIN组的天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平较低。与对照组和CIN组相比，顺铂组的总组织学损伤更大。
结论
顺铂可能通过增加细胞因子水平导致肝损伤。它可能通过增加碳酸酐酶II（CA-II）酶水平和降低CPS-1酶水平来增加氧化应激诱导的组织损伤。英夫利昔单抗通过阻断TNF-α降低顺铂诱导的肝损伤，并且它还可能通过调节CPS-1和CA-II酶水平来预防肝损伤。
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