Divisions of Nephrology, Department of Pediatrics .
Ren Fail. 2013;35(10):1376-81. doi: 10.3109/0886022X.2013.828359. Epub 2013 Sep 2.
We aimed to investigate the underlying mechanisms responsible for the renoprotective effects of pentoxifylline (PTX) in gentamicin (GEN)-induced nephropathy. On this purpose, 26 female Wistar rats (200-250 g) were included and four groups were formed. The first one was the control group (n:5). The rats in other groups (n:7 for each) received 50 mg/kg twice daily intraperitoneal (i.p.) PTX, 100 mg/kg i.p. GEN and both GEN and PTX at the same doses for consecutive 8 days, respectively. Rats were weighed both at the beginning and end of the study. After the last dose, 24-hour urines were collected and the rats were sacrificed. Blood samples and kidney tissues were obtained for biochemical, histological, oxidative stress, and apoptotic parameters. Body weights were similar in all groups at the beginning of the study. Rats in GEN group had significant weight loss, tubular damage, and increased apoptosis, while GEN + PTX group had significantly better outcomes. Scr, urinary protein/creatinine, and TBARS levels were significantly higher and Ccr and SOD levels were significantly lower in GEN and GEN + PTX groups in comparison to control and PTX groups, but the levels were similar between GEN and GEN + PTX groups. In conclusion, concomitant administration of PTX provides renoprotection via suppressing apoptosis in GEN-induced nephropathy.
我们旨在研究己酮可可碱(PTX)在庆大霉素(GEN)诱导的肾病中具有肾保护作用的潜在机制。为此,将 26 只雌性 Wistar 大鼠(200-250g)纳入研究并分为四组。第一组为对照组(n=5)。其他组(每组 n=7)的大鼠分别接受 50mg/kg 己酮可可碱,2 次/天,腹腔内(i.p.)注射;100mg/kg 庆大霉素,2 次/天,腹腔内注射;以及两种药物以相同剂量连续 8 天给药。大鼠在研究开始和结束时称重。最后一次给药后收集 24 小时尿液,处死大鼠。采集血样和肾组织用于生化、组织学、氧化应激和凋亡参数检测。研究开始时,所有组的体重均相似。GEN 组大鼠体重显著减轻,肾小管损伤,凋亡增加,而 GEN+PTX 组的结果明显更好。与对照组和 PTX 组相比,GEN 和 GEN+PTX 组的血清肌酐(Scr)、尿蛋白/肌酐(UPC)和 TBARS 水平显著升高,而肌酐清除率(Ccr)和超氧化物歧化酶(SOD)水平显著降低,但 GEN 和 GEN+PTX 组之间的水平相似。总之,PTX 的联合给药通过抑制 GEN 诱导的肾病中的细胞凋亡提供了肾保护作用。