Koyuncu Ismail, Kocyigit Abdurrahim, Gonel Ataman, Arslan Erkan, Durgun Mustafa
Department of Biochemistry, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.
Biochem Res Int. 2017;2017:9478958. doi: 10.1155/2017/9478958. Epub 2017 Aug 28.
The aim of this study is to examine the protective effect of naringenin-oxime (NOX) on cisplatin-induced major organ toxicity and DNA damage in rats. Thirty-five male Wistar albino rats were equally split into five groups as follows: control (i.p., 0.1 ml of saline), Cis administration (i.p., 7 mg/kg b.w.), NOX treatment (i.p., 20 mg/kg b.w., daily for ten days), Cis + NOX20, and Cis + NOX40 combination (i.p., 20 and 40 mg/kg b.w., daily for ten days). Serum and peripheral blood mononuclear leukocytes (PBMC) were obtained from blood. Malondialdehyde, glutathione, total antioxidant and oxidant status, and catalase were measured in serum, liver, and kidney, and oxidative stress index was calculated. In parallel, paraoxonase and arylesterase activities were tested in liver and serum. We used 8-OHdOG as a marker for DNA damage in serum via ELISA and in PMBC via comet assay. Treatment with Cis elevated the levels of serum biochemical parameters, oxidative stress, and DNA damage. Pretreatments of NOX restored biochemical and oxidative stress parameters in serum, renal, and liver tissues ( < 0.01) and reduced 8-OHdG level, a finding further supported by comet assay in PBMC. Observations of the present study support the fact that treatment with NOX prevents Cis-induced hepatotoxicity, nephrotoxicity, and genotoxicity by restoring antioxidant system.
本研究的目的是检测柚皮素肟(NOX)对顺铂诱导的大鼠主要器官毒性和DNA损伤的保护作用。将35只雄性Wistar白化大鼠平均分为五组,如下:对照组(腹腔注射0.1 ml生理盐水)、顺铂给药组(腹腔注射7 mg/kg体重)、NOX治疗组(腹腔注射20 mg/kg体重,每日一次,共十天)、顺铂+NOX20组和顺铂+NOX40联合组(腹腔注射20和40 mg/kg体重,每日一次,共十天)。从血液中获取血清和外周血单核白细胞(PBMC)。检测血清、肝脏和肾脏中的丙二醛、谷胱甘肽、总抗氧化和氧化状态以及过氧化氢酶,并计算氧化应激指数。同时,检测肝脏和血清中的对氧磷酶和芳基酯酶活性。我们通过ELISA检测血清中的DNA损伤标志物8-羟基脱氧鸟苷(8-OHdOG),并通过彗星试验检测PBMC中的8-OHdOG。顺铂治疗可提高血清生化参数、氧化应激和DNA损伤水平。NOX预处理可恢复血清、肾脏和肝脏组织中的生化和氧化应激参数(<0.01),并降低8-OHdG水平,PBMC中的彗星试验进一步支持了这一发现。本研究的观察结果支持以下事实:NOX治疗通过恢复抗氧化系统来预防顺铂诱导的肝毒性、肾毒性和遗传毒性。