Tariq M, Morais C, Sobki S, Al Sulaiman M, Al Khader A
Department of Nephrology and Research Center, Armed Forces Hospital, Riyadh, Saudi Arabia.
Ren Fail. 2000;22(5):545-60. doi: 10.1081/jdi-100100896.
Psychoactive drugs provide essential intervention in the care of transplant recipients, yet little is known of their interaction with immunosuppressants such as cyclosporin (CSA). Lithium (Li) is an invaluable drug for the treatment of manic disorders in organ transplant patients. As both these drugs are known to produce renal toxicity, the concomitant use of CSA and Li may be potentially harmful. The present study was undertaken to investigate the effect of CSA and Li chloride individually and in combination on renal structure and function of rats. Male Sprague-Dawley rats were divided into the following eight groups of seven animals each: group I, control (vehicle only); group 2, Li (2 mEq/ kg i.p.) alone; group 3, CSA 12.5 mg/kg (subcutaneous); group 4, CSA 25 mg/kg; group 5, CSA 50 mg/kg; group 6, CSA 12.5 mg/kg + Li; group 7, CSA 25 mg/kg + Li; and group 8, CSA 50 mg/kg + Li. The drugs were given once a day for seven days; Li being administered 30 min before CSA. Twenty four hours after the last dose of drugs the animals were sacrificed and blood samples were analyzed for blood urea nitrogen (BUN), serum creatinine (SCr), CSA and Li levels. The left kidney was analyzed for malondialdehyde (MDA) and conjugated dienes (CD) levels and right kidney was used for histopathological studies. Our results showed that Li alone did not produce any significant renal toxicity, whereas CSA dose dependently caused structural and functional changes in kidneys. However, significantly higher structural and functional impairment was observed in the animals treated with Li plus CSA as compared to CSA alone treated animals. Several fold increase in blood Li level was also noticed in the rats concomitantly treated with CSA and Li. A significant increase in MDA and CD in the rats treated with CSA plus Li suggests the role of oxidative stress in drug induced nephrotoxicity. These findings clearly demonstrate that even non toxic doses of Li may significantly exacerbate CSA induced nephrotoxicity in rats. The enhanced nephrotoxicity following concomitant use of these drugs may be attributed to significant increase in the bioavailability of Li and enhanced oxidative stress. Further clinical studies are warranted to investigate the interaction of these nephrotoxic drugs in human subjects.
精神活性药物在移植受者的护理中提供了重要的干预措施，但人们对它们与环孢素（CSA）等免疫抑制剂的相互作用知之甚少。锂（Li）是治疗器官移植患者躁狂症的一种重要药物。由于已知这两种药物都会产生肾毒性，CSA和Li同时使用可能具有潜在危害。本研究旨在调查CSA和氯化锂单独使用及联合使用对大鼠肾脏结构和功能的影响。将雄性Sprague-Dawley大鼠分为以下八组，每组七只动物：第一组，对照组（仅给予赋形剂）；第二组，单独使用Li（腹腔注射2 mEq/kg）；第三组，CSA 12.5 mg/kg（皮下注射）；第四组，CSA 25 mg/kg；第五组，CSA 50 mg/kg；第六组，CSA 12.5 mg/kg + Li；第七组，CSA 25 mg/kg + Li；第八组，CSA 50 mg/kg + Li。每天给药一次，持续七天；Li在CSA给药前30分钟给予。在最后一剂药物给药24小时后，处死动物并分析血样中的血尿素氮（BUN）、血清肌酐（SCr）、CSA和Li水平。分析左肾中的丙二醛（MDA）和共轭二烯（CD）水平，右肾用于组织病理学研究。我们的结果表明，单独使用Li不会产生任何显著的肾毒性，而CSA会剂量依赖性地引起肾脏的结构和功能变化。然而，与单独使用CSA治疗的动物相比，同时使用Li和CSA治疗的动物观察到明显更高的结构和功能损害。在同时接受CSA和Li治疗的大鼠中，血Li水平也有几倍的升高。CSA加Li治疗的大鼠中MDA和CD显著增加，表明氧化应激在药物诱导的肾毒性中起作用。这些发现清楚地表明，即使是无毒剂量 的Li也可能显著加剧CSA诱导的大鼠肾毒性。这些药物同时使用后肾毒性增强可能归因于Li的生物利用度显著增加和氧化应激增强。有必要进行进一步的临床研究来调查这些肾毒性药物在人类受试者中的相互作用。
