Uekama K, Shiotami K, Irie T, Ishimaru Y, Pitha J
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
J Pharm Pharmacol. 1993 Aug;45(8):745-7. doi: 10.1111/j.2042-7158.1993.tb07100.x.
The effects of cyclodextrin sulphates on the development of rat renal dysfunction induced with gentamicin, an aminoglycoside antibiotic, were studied. Daily subcutaneous injection of gentamicin (100 mg kg-1, 14 days) developed nephrotoxicity in the rat as assessed by an increase in serum urea nitrogen and histopathological changes in the renal cortex. When cyclodextrin sulphates were given intraperitoneally at 300 mg kg-1 at 6 h intervals after gentamicin administration, they protected the rat against the drug-induced renal impairment, while the parent cyclodextrins were ineffective. Since post-administration of cyclodextrin sulphates did not reduce the total amount of gentamicin accumulated in the kidney, the protection may occur through interference with intracellular events leading from the drug accumulation to nephrotoxicity. These results suggest that cyclodextrin sulphates are particularly effective in preventing renal failure associated with aminoglycoside treatment.
研究了硫酸环糊精对由氨基糖苷类抗生素庆大霉素诱导的大鼠肾功能障碍发展的影响。通过血清尿素氮增加和肾皮质组织病理学变化评估,每日皮下注射庆大霉素(100 mg kg-1,共14天)可使大鼠产生肾毒性。在给予庆大霉素后,每隔6小时腹腔注射300 mg kg-1硫酸环糊精,可保护大鼠免受药物诱导的肾损伤,而母体环糊精则无效。由于硫酸环糊精给药后并未减少肾脏中积累的庆大霉素总量,这种保护作用可能是通过干扰从药物积累到肾毒性的细胞内事件而发生的。这些结果表明,硫酸环糊精在预防与氨基糖苷类治疗相关的肾衰竭方面特别有效。