Khoshnoud Saeideh, Mohseni Kouchesfahani Homa, Nabiuni Mohammad
Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Cell J. 2017 Jul-Sep;19(2):306-313. doi: 10.22074/cellj.2016.3957. Epub 2017 Feb 22.
Methotrexate (MTX) is an antimetabolite drug commonly prescribed for the various cancers and autoimmune diseases. Despite its considerable therapeutic effects, nephrotoxicity is the most important side-effect of treatment with MTX. Aquaporin1 (AQP1) is a water channel proteins which is present in mammalian kidney. Raspberry fruit with antioxidant properties is able to protect biological systems from the harmful effects of free radicals. The purpose of this study was to investigate the effect of raspberry extract on expression of AQP1 and the MTX-induced nephrotoxicity in rats.
In this experimental study, 60 adult male Wistar rats were divided into nine groups including control, sham, MTX treated group [single dose of 20 mg/kg of body weight (BW) MTX at the third day], raspberry treated groups [intraperitoneal (I.P) injection of 100, 200, 400 mg/kg of BW raspberry extract for ten consecutive days], MTX and raspberry treated groups. At day 11, rats were sacrificed via chloroform inhalation and kidney tissues were fixed in formalin solution for histological and immunohistochemistry analysis. The serological assays for urea, creatinine, uric acid and interleukin-6 (IL-6) levels were also performed.
MTX elevated serum level of the urea, creatinine, uric acid, IL-6, renal tissue damage and decreased the AQP1 expression level. Raspberry fruit extract improved the kidney function and reduced side effects of MTX in treated rats. Expression of AQP1, in a dose dependent manner was also ameliorated, as compared to control group.
According to the findings of this study, it can be concluded that biological activity of compounds presented in raspberry fruit extract especially anthocyanins may have chemo-protective effect on kidney function and AQP1 expression in rats treated by MTX.
甲氨蝶呤（MTX）是一种常用于治疗各种癌症和自身免疫性疾病的抗代谢药物。尽管其具有显著的治疗效果，但肾毒性是MTX治疗最重要的副作用。水通道蛋白1（AQP1）是一种存在于哺乳动物肾脏中的水通道蛋白。具有抗氧化特性的树莓果实能够保护生物系统免受自由基的有害影响。本研究的目的是探讨树莓提取物对大鼠AQP1表达及MTX诱导的肾毒性的影响。
在本实验研究中，60只成年雄性Wistar大鼠被分为九组，包括对照组、假手术组、MTX治疗组[在第三天单次给予20 mg/kg体重（BW）的MTX]、树莓治疗组[连续十天腹腔注射（I.P）100、200、400 mg/kg BW的树莓提取物]、MTX与树莓联合治疗组。在第11天，通过吸入氯仿处死大鼠，将肾脏组织固定在福尔马林溶液中进行组织学和免疫组织化学分析。还进行了尿素、肌酐、尿酸和白细胞介素-6（IL-6）水平的血清学检测。
MTX升高了尿素、肌酐、尿酸、IL-6的血清水平，造成肾组织损伤，并降低了AQP1表达水平。树莓果实提取物改善了治疗大鼠的肾功能并减轻了MTX的副作用。与对照组相比，AQP1的表达也呈剂量依赖性改善。
根据本研究结果，可以得出结论，树莓果实提取物中所含化合物尤其是花青素的生物活性可能对MTX治疗的大鼠的肾功能和AQP1表达具有化学保护作用。
