Natarajan Kasthuri, Abraham Premila, Kota Rekha, Selvakumar Dhayakani
Department of Biochemistry, Christian Medical College, Bagayam, Vellore, Tamil Nadu.
Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu.
J Basic Clin Physiol Pharmacol. 2017 May 1;28(3):239-247. doi: 10.1515/jbcpp-2016-0099.
One of the major toxic side effects of methotrexate (MTX) is enterocolitis, for which there is no efficient standard treatment. Nitric oxide overproduction has been reported to play an important role in MTX-induced mucositis. This study was designed to investigate whether pretreatment with aminoguanidine (AG) - a selective iNOS inhibitor - prevents MTX-induced mucositis in rats.
Rats were pretreated with AG (30 and 50 mg/kg body weight) i.p. daily 1 h before MTX (7 mg/kg body weight) administration for 3 consecutive days. After the final dose of MTX, the rats were killed, and the small intestines were used for analysis.
The small intestines of MTX-treated rats showed moderate to severe injury. Pretreatment with AG had a dose-dependent protective effect on MTX-induced mucositis. AG pretreatment reduced iNOS protein levels, mucosal nitric oxide levels, and protein tyrosine nitration. AG pretreatment also restored the activities of electron transport chain (ETC) complexes, vital tricarboxylic acid (TCA cycle) enzymes, and mitochondrial antioxidant enzymes.
These findings suggest that AG is beneficial in ameliorating MTX-induced enteritis in rats.
甲氨蝶呤（MTX）的主要毒副作用之一是小肠结肠炎，对此尚无有效的标准治疗方法。据报道，一氧化氮过量产生在MTX诱导的粘膜炎中起重要作用。本研究旨在调查用氨基胍（AG）——一种选择性诱导型一氧化氮合酶抑制剂——预处理是否能预防MTX诱导的大鼠粘膜炎。
大鼠在腹腔注射MTX（7mg/kg体重）前1小时每天腹腔注射AG（30和50mg/kg体重），连续3天。在最后一剂MTX后，处死大鼠，取小肠进行分析。
MTX处理的大鼠小肠显示出中度至重度损伤。AG预处理对MTX诱导的粘膜炎有剂量依赖性保护作用。AG预处理降低了诱导型一氧化氮合酶蛋白水平、粘膜一氧化氮水平和蛋白酪氨酸硝化作用。AG预处理还恢复了电子传递链（ETC）复合物、重要的三羧酸（TCA循环）酶和线粒体抗氧化酶的活性。
这些发现表明AG对改善MTX诱导的大鼠肠炎有益。
