Al-Majed Abdulhakeem A, Abd-Allah Adel R A, Al-Rikabi Ammar C, Al-Shabanah Othman A, Mostafa Adel M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh 11451, Kingdom of Saudi Arabia.
J Biochem Mol Toxicol. 2003;17(3):146-53. doi: 10.1002/jbt.10072.
It has been recently postulated from our laboratory that Arabic gum (AG) offers a protective effect in the kidney of rats against nephrotoxicity induced by gentamicin via inhibiting lipid peroxidation. It has also recently shown a powerful antioxidant effect through scavenging superoxide anions. In this study we utilized a rat model of cisplatin (CP)-induced nephrotoxicity to determine its peak time following (1, 2, 5, and 7 days) of a single CP (7.5 mg/kg, i.p.) injection. Also, a possible protective effect of cotreatment with AG (7.5 g/kg/day p.o.) on CP-induced nephrotoxicity was investigated. Biochemical as well as histological assessments were carried out. CP-induced nephrotoxicity was manifested by significant elevations of the functional parameters blood urea, serum creatinine, and kidney/body weight ratio. Maximum toxic effects of CP were observed 5 days after its injection, while it started after day 1 in the biochemical parameters, such as glutathione depletion in the kidney tissue with concomitant increases in lipid peroxides and platinum content. Additionally, severe necrosis and desquamation of tubular epithelial cells in renal cortex as well as interstitial nephritis were observed after 5 days in CP-treated animals. Five days after AG cotreatment with CP did not protect the kidney from the damaging effects of CP. However, it significantly reduced CP-induced lipid peroxidation. These findings suggest that lipid peroxidation is not the main cause of CP-induced nephrotoxicity but it is rather more dependent on other factors such as platinum disposition in renal interstitial tubules.
最近我们实验室推测,阿拉伯胶(AG)可通过抑制脂质过氧化,对庆大霉素诱导的大鼠肾毒性起到肾脏保护作用。最近还发现它通过清除超氧阴离子具有强大的抗氧化作用。在本研究中,我们利用顺铂(CP)诱导的肾毒性大鼠模型,确定单次腹腔注射CP(7.5mg/kg)后(1、2、5和7天)的峰值时间。此外,还研究了AG(7.5g/kg/天,口服)联合治疗对CP诱导的肾毒性的可能保护作用。进行了生化和组织学评估。CP诱导的肾毒性表现为功能参数血尿素、血清肌酐和肾/体重比显著升高。CP注射后5天观察到最大毒性作用,而在生化参数方面,在第1天后开始出现,如肾组织中谷胱甘肽耗竭,同时脂质过氧化物和铂含量增加。此外,在CP处理的动物中,5天后观察到肾皮质肾小管上皮细胞严重坏死和脱落以及间质性肾炎。AG与CP联合治疗5天后,未能保护肾脏免受CP的损伤作用。然而,它显著降低了CP诱导的脂质过氧化。这些发现表明,脂质过氧化不是CP诱导肾毒性的主要原因,而是更多地依赖于其他因素,如铂在肾间质小管中的分布。