Khalifa Eman Aly, Nabil Ahmed Ahmed, Hashem Khalid Shaaban, Allah Ahmad Gad
Department of Biotechnology and Life Sciences, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt.
International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), Tsukuba, Japan.
Int J Inflam. 2020 Apr 9;2020:5369797. doi: 10.1155/2020/5369797. eCollection 2020.
Nephrotoxicity of cisplatin has been recognized since its introduction more than 25 years ago. However, despite intense efforts to develop less toxic and equally effective alternatives, cisplatin continues to be widely prescribed. . The study is aimed at assessing the possible prophylactic effect of coenzyme Q10 (CoQ10) and alpha-lipoic acid (ALA) (separately or in combination) on experimentally cisplatin-induced nephrotoxicity. . An experimental study was performed on adult male albino rats ( = 40), weighing 200-250 g. Rats were randomly divided into 5 groups: group I (normal saline control), group II (cisplatin control), group III (CoQ10 and cisplatin), group IV (ALA and cisplatin), and group V (CoQ10, ALA, and cisplatin). CoQ10 and/or ALA were given as pretreatment for 9 days, followed by cisplatin injection in the 10th day of the study, followed by a short posttreatment course for 3 days. Renal functions, tissue antioxidant activity, and inflammatory markers (tumor necrosis factor, TNF) were estimated along with histopathological study.
Renal function tests and urinary proteins were significantly higher within group II compared with other groups ( value <0.001). Creatinine clearance was significantly higher with combination therapy (group V compared to other groups). Both TNF and malondialdehyde (MDA) were significantly higher within group II whereas GSH content, catalase, and superoxide dismutase (SOD) were significantly lower in group II. MDA level was significantly lower when combination therapy was used. Marked renal damage was histologically detected in the cisplatin group, whereas the least renal damage was noticed in the combination group.
The study confirmed the role of antioxidants in preventing nephrotoxicity caused by cisplatin; the prophylactic effect of combined therapy with CoQ10 and ALA is superior to that of monotherapy.
顺铂的肾毒性自25多年前被引入以来就已为人所知。然而,尽管人们付出了巨大努力来开发毒性更低且效果相当的替代药物,但顺铂仍被广泛使用。本研究旨在评估辅酶Q10(CoQ10)和α-硫辛酸(ALA)(单独或联合使用)对实验性顺铂诱导的肾毒性的可能预防作用。对体重200 - 250克的成年雄性白化大鼠(n = 40)进行了一项实验研究。大鼠被随机分为5组:第一组(生理盐水对照组),第二组(顺铂对照组),第三组(CoQ10与顺铂组),第四组(ALA与顺铂组),第五组(CoQ10、ALA与顺铂组)。CoQ10和/或ALA作为预处理给药9天,在研究的第10天注射顺铂,随后进行为期3天的短期后续治疗。评估了肾功能、组织抗氧化活性和炎症标志物(肿瘤坏死因子,TNF)以及组织病理学研究。
与其他组相比,第二组的肾功能测试和尿蛋白显著更高(p值<0.001)。联合治疗组(第五组与其他组相比)的肌酐清除率显著更高。第二组中的TNF和丙二醛(MDA)均显著更高,而第二组中的谷胱甘肽(GSH)含量、过氧化氢酶和超氧化物歧化酶(SOD)显著更低。使用联合治疗时MDA水平显著更低。在顺铂组中组织学检测到明显的肾损伤,而联合组中观察到的肾损伤最小。
该研究证实了抗氧化剂在预防顺铂引起的肾毒性中的作用;CoQ10和ALA联合治疗的预防效果优于单一疗法。