Shihab-Eldeen A, Owunwanne A, Junaid T A, Yacoub T
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait.
Hum Exp Toxicol. 1996 Nov;15(11):867-71. doi: 10.1177/096032719601501101.
Iodine-125 HIPDM was evaluated as a screening agent for studying multiorgan toxicity due to Cyclosporine-A (CsA) and the results were compared to histopathological findings of the tissues. The rats were injected subcutaneously with 50 mg/kg (body weight) of CsA or with equal volume of the vehicle, Cremophor-EL, for 7 consecutive days. A dose of 10 microCi of I-125 HIPDM was injected intravenously at the end of the treatment period. The results indicated that there was a significant increase in the uptake of I-125 HIPDM in the kidney, liver, heart and blood compared to control rats (P < 0.05). However, there was a significant decrease in the uptake of I-125 HIPDM in the spleen compared to control animals (P < 0.001). The lung and brain of CsA treated rats showed no change in the uptake of I-125 HIPDM when compared to control rats. The change in the uptake of I-125 HIPDM in these organs was assumed to indicate tissue response to the toxic effects of CsA. The radiopharmaceutical results were comparable with the histopathological findings in which the organs showed varying degrees of tissue degeneration. It is concluded that the lipophilic radiopharmaceutical, I-125 HIPDM, can be used as an effective screening agent to study multiorgan toxicity due to CsA.
对碘 - 125 HIPDM作为研究环孢素A（CsA）所致多器官毒性的筛选剂进行了评估，并将结果与组织的组织病理学发现进行了比较。将大鼠皮下注射50毫克/千克（体重）的CsA或等体积的溶媒聚氧乙烯蓖麻油（Cremophor - EL），连续7天。在治疗期结束时静脉注射10微居里的I - 125 HIPDM。结果表明，与对照大鼠相比，肾脏、肝脏、心脏和血液中I - 125 HIPDM的摄取量显著增加（P < 0.05）。然而，与对照动物相比，脾脏中I - 125 HIPDM的摄取量显著降低（P < 0.001）。与对照大鼠相比，CsA处理大鼠的肺和脑在I - 125 HIPDM摄取方面无变化。这些器官中I - 125 HIPDM摄取的变化被认为表明组织对CsA毒性作用的反应。放射性药物结果与组织病理学发现具有可比性，其中各器官显示出不同程度的组织变性。得出的结论是，亲脂性放射性药物I - 125 HIPDM可用作研究CsA所致多器官毒性的有效筛选剂。
