Department of Urology, Tepecik Training and Research Hospital, Yenişehir Mah, Gaziler Cad. No:468, Konak, 35100, İzmir, Turkey.
Department of Internal Medicine, Tepecik Training and Research Hospital, İzmir, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Feb;392(2):159-164. doi: 10.1007/s00210-018-01603-0. Epub 2019 Jan 4.
The aim of this study is to investigate the effects of all-trans retinoic acid (ATRA) use on cisplatin (CP)-induced nephrotoxicty. Twenty-eight rats were randomly divided into four groups. The rats in the control group were injected a single dose of 1 ml/kg saline intra-peritoneally (IP) during 10 days. The rats in the ATRA group were injected a single dose of ATRA during 10 days. The rats in the ATRA+CP group were injected a single dose of CP on the fourth day of the 10 days of ATRA treatment. The rats in the CP group were injected a single dose of CP on the fourth day of 10 days without administering a treatment. After treatment, the groups were compared with regard to total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels in renal tissue and renal histopathology. The serum creatinine and urea values were statistically significantly higher in the CP group compared to the other groups. The serum creatinine and urea values were statistically significantly lower in the ATRA+CP group when compared to the CP group. Although the TOS and OSI levels were found to be lower in the ATRA+CP group compared to the CP group, the difference was not statistically significant. Administration of ATRA together with CP was observed to reduce the histopathologic destruction in the kidney and lead to mild tubular degeneration, vacuolization, and necrosis (57.1% grade 1; 28.6% grade2, and 14.3% grade 3 necrosis). The results of the present study have revealed that ATRA administration ameliorates CP-induced nephrotoxicity; however, further studies are required to identify this issue before clinical application.
本研究旨在探讨全反式维甲酸(ATRA)对顺铂(CP)诱导的肾毒性的影响。28 只大鼠随机分为四组。对照组大鼠在 10 天内每天腹腔注射 1ml/kg 生理盐水。ATRA 组大鼠在 10 天内每天注射一次 ATRA。ATRA+CP 组大鼠在 ATRA 治疗的第 10 天第四天注射一次 CP。CP 组大鼠在不给予治疗的情况下,在第 10 天的第四天注射一次 CP。治疗后,比较各组大鼠肾组织总抗氧化状态(TAS)、总氧化状态(TOS)和氧化应激指数(OSI)水平及肾组织病理学变化。与其他组相比,CP 组血清肌酐和尿素值明显升高。与 CP 组相比,ATRA+CP 组血清肌酐和尿素值明显降低。与 CP 组相比,ATRA+CP 组 TOS 和 OSI 水平较低,但差异无统计学意义。同时给予 ATRA 和 CP 可减少肾脏的组织病理学破坏,导致轻度肾小管变性、空泡化和坏死(1 级 57.1%;2 级 28.6%;3 级 14.3%坏死)。本研究结果表明,ATRA 可减轻 CP 诱导的肾毒性;然而,在临床应用前,还需要进一步研究来确定这一问题。