Ozcicek Adalet, Ozcicek Fatih, Cimen Ferda Keskin, Mammadov Renad, Cankaya Murat, Ezmeci Talat, Altuner Durdu
Department of Internal Medicine, Faculty of Medicine, Erzincan University, Turkey.
Department of Pathology, Faculty of Medicine, Erzincan University, Turkey.
Adv Clin Exp Med. 2018 Dec;27(12):1643-1650. doi: 10.17219/acem/75775.
Oxidative stress and interleukin-1 beta (IL-1β) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin.
The objective of this study was to investigate the effect of anakinra, which is an IL-1β receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses.
The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1β. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA).
The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1β gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1β gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1β at a dose of 100 mg/kg compared to a 50 mg/kg dose.
Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.
据报道，氧化应激和白细胞介素-1β（IL-1β）在顺铂诱导的肾毒性发病机制中起作用。
本研究的目的是通过生化、基因表达和组织病理学分析，研究IL-1β受体拮抗剂阿那白滞素对大鼠顺铂诱导的肾毒性的影响。
本研究设计为4组。连续1周，对照组（C）和顺铂组（Cis）给予蒸馏水，而顺铂+阿那白滞素50（Cis + ANA50）组和顺铂+阿那白滞素100（Cis + ANA100）组分别腹腔注射50 mg/kg和100 mg/kg的阿那白滞素。Cis组、Cis + ANA50组和Cis + ANA100组腹腔注射2.5 mg/kg剂量的顺铂，持续7天。处死后，提取每只大鼠的肾组织，评估丙二醛（MDA）和总谷胱甘肽（tGSH）水平，并进行IL-1β的基因表达分析。对肾组织进行组织病理学评估。数据采用单因素方差分析（ANOVA）进行统计分析。
与其他组相比，顺铂给药组（Cis组）的MDA水平较高（4.75±0.25 nmol/mL；p < 0.001），tGSH水平较低（1.80±0.35 mg/L；p < 0.001）。与其他组相比，顺铂还增加了IL-1β基因表达（6.33±0.27基因表达水平；p < 0.001）。观察到阿那白滞素对顺铂诱导的MDA和tGSH水平以及IL-1β基因表达的影响使这些结果发生了逆转（p < 0.05）。与50 mg/kg剂量相比，阿那白滞素在100 mg/kg剂量时能更好地预防MDA和IL-1β水平的升高。
阿那白滞素以剂量依赖的方式预防顺铂诱导的肾氧化损伤。这一结果表明，阿那白滞素可能对治疗顺铂诱导的肾损伤有用。
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