Al-Harbi Naif O, Imam Faisal, Nadeem Ahmed, Al-Harbi Mohammed M, Iqbal Muzaffar, Rahman Shakilur, Al-Hosaini Khalid A, Bahashwan Saleh
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University , Riyadh , KSA .
Toxicol Mech Methods. 2014 Dec;24(9):697-702. doi: 10.3109/15376516.2014.963773. Epub 2014 Sep 23.
Tacrolimus (TAC), a calcineurin inhibitor, is commonly used as an immunosuppressive agent in organ transplantation, but its clinical use may be limited due to cardiotoxicity. Olmesartan (OLM; angiotensin receptor blocker) and aliskiren (ALK; renin inhibitor) may attenuate cardiotoxicity induced by TAC by inhibition of renin-angiotensin aldosterone system.
The aim of this study was to evaluate the effect of OLM and ALK on TAC-induced cardiotoxicity.
Male Wistar albino rats weighing 200-250 g (10-12 weeks old) were used in this study. Animals were divided into four groups. Group 1 received normal saline, group 2 received TAC (2 mg/kg, intraperitoneally for 14 d), group 3 received OLM (2 mg/kg, p.o. for 28 d) + TAC and group 4 received ALK (50 mg/kg, p.o. for 28 d) + TAC. TAC-induced cardiotoxicity was assessed biochemically and histopathologically.
Treatment with OLM or ALK decreased the TAC-induced changes in biochemical markers of cardiotoxicity such as serum aspartate transaminase, creatine kinase and lactate dehydrogenase. OLM or ALK also attenuated the effects of TAC on oxidant-antioxidant parameters such as malondialdehyde, reduced glutathione and catalase. Histopathological and ultrastructural studies showed that OLM or ALK also attenuated TAC-induced cardiotoxicity.
These results suggest that OLM as well as ALK has protective effects against TAC-induced cardiotoxicity; implying that angiotensin receptor blocker or renin inhibitor, respectively, may counteract cardiotoxicity associated with immunosuppressant use.
他克莫司（TAC）是一种钙调神经磷酸酶抑制剂，在器官移植中常用作免疫抑制剂，但其临床应用可能因心脏毒性而受到限制。奥美沙坦（OLM；血管紧张素受体阻滞剂）和阿利吉仑（ALK；肾素抑制剂）可能通过抑制肾素 - 血管紧张素 - 醛固酮系统减轻TAC诱导的心脏毒性。
本研究旨在评估OLM和ALK对TAC诱导的心脏毒性的影响。
本研究使用体重200 - 250克（10 - 12周龄）的雄性Wistar白化大鼠。动物分为四组。第1组接受生理盐水，第2组接受TAC（2毫克/千克，腹腔注射14天），第3组接受OLM（2毫克/千克，口服28天）+ TAC，第4组接受ALK（50毫克/千克，口服28天）+ TAC。通过生化和组织病理学方法评估TAC诱导的心脏毒性。
OLM或ALK治疗可降低TAC诱导的心脏毒性生化标志物变化，如血清天冬氨酸转氨酶、肌酸激酶和乳酸脱氢酶。OLM或ALK还减弱了TAC对氧化应激 - 抗氧化参数如丙二醛、还原型谷胱甘肽和过氧化氢酶的影响。组织病理学和超微结构研究表明，OLM或ALK也减轻了TAC诱导的心脏毒性。
这些结果表明，OLM和ALK对TAC诱导的心脏毒性均具有保护作用；这意味着血管紧张素受体阻滞剂或肾素抑制剂分别可能抵消与免疫抑制剂使用相关的心脏毒性。
