Department of Medical Oncology, Faculty of Medicine, Trakya University, Edirne, Turkey.
Med Oncol. 2011 Dec;28 Suppl 1:S690-6. doi: 10.1007/s12032-010-9746-2. Epub 2010 Dec 8.
We aimed to compare the protective effect of L-carnitine (CAR) and amifostine (AMF) against cisplatin (CDDP)-induced nephrotoxicity through biochemical markers and histopathological evaluation. Fifty-seven Wistar albino male rats were randomly classified into six groups, which were AMF+CDDP (n = 11; 200 mg/kg AMF 30 min prior to 7 mg/kg CDDP), CAR+CDDP (n = 11; 300 mg/kg CAR 30 min prior to 7 mg/kg CDDP), CDDP (n = 11; 1 mL/kg isotonic saline 30 min prior to 7 mg/kg CDDP), AMF (n = 8; 200 mg/kg AMF alone), CAR (n = 8; 300 mg/kg CAR alone), and control (n = 8; 1 mL/kg isotonic saline alone). All drugs were given intraperitoneally. Five days after medication, animals were killed, and samples of blood and kidney tissues were collected for biochemical and histopathological evaluation. The serum urea level was highest in AMF+CDDP group among CDDP-applied groups without statistical significance (median, range: 88, 56-21 mg/dL; P > 0.05). There was no statistical significance among CDDP-applied groups in terms of creatinine level (P > 0.05). In the AMF+CDDP group, the median glomerular, tubular, and tubulointerstitial inflammatory damage scores were significantly higher than the other CDDP-applied groups (P < 0.001). The difference between CAR+CDDP and CDDP groups was not statistically significant in terms of renal damage scores. AMF+CDDP group had significantly higher median total nephrotoxicity score than all the other groups (P < 0.001). To conclude, AMF or CAR has no protective effect on CDDP-induced nephrotoxicity. Furthermore, our findings suggest that application of AMF before CDDP may enhance CDDP-induced nephrotoxicity histopathologically.
我们旨在通过生化标志物和组织病理学评估比较左旋肉碱 (CAR) 和氨磷汀 (AMF) 对顺铂 (CDDP) 诱导的肾毒性的保护作用。57 只 Wistar 白化雄性大鼠被随机分为六组,即 AMF+CDDP(n = 11;200mg/kg AMF 在给予 7mg/kg CDDP 前 30 分钟)、CAR+CDDP(n = 11;300mg/kg CAR 在给予 7mg/kg CDDP 前 30 分钟)、CDDP(n = 11;1mL/kg 等渗盐水在给予 7mg/kg CDDP 前 30 分钟)、AMF(n = 8;200mg/kg AMF 单独)、CAR(n = 8;300mg/kg CAR 单独)和对照组(n = 8;1mL/kg 等渗盐水单独)。所有药物均腹腔内给药。给药后 5 天,处死动物,采集血液和肾脏组织样本进行生化和组织病理学评估。在接受 CDDP 治疗的各组中,AMF+CDDP 组的血清尿素水平最高,但无统计学意义(中位数,范围:88,56-21mg/dL;P>0.05)。在接受 CDDP 治疗的各组中,肌酐水平无统计学意义(P>0.05)。在 AMF+CDDP 组,肾小球、肾小管和肾小管间质性炎症损伤评分的中位数明显高于其他接受 CDDP 治疗的组(P<0.001)。CAR+CDDP 组与 CDDP 组之间的肾脏损伤评分无统计学差异。AMF+CDDP 组的总肾毒性评分中位数明显高于其他所有组(P<0.001)。总之,AMF 或 CAR 对 CDDP 诱导的肾毒性没有保护作用。此外,我们的研究结果表明,在给予 CDDP 之前应用 AMF 可能会增强 CDDP 诱导的肾毒性的组织病理学表现。