Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats
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- 作者：Alaa E. El-Sisi (Professor of Pharmacology ; Toxicology) ; Samia S. Sokar (Professor of Pharmacology ; Toxicology) ; Sally E. Abu-Risha (Lecturer of Pharmacology ; Toxicology) ; Hanaa A. Ibrahim ; hanaaadel_2011@yahoo.com (Instructor of Pharmacology ; Toxicology)
- 关键词：Renal ischemia/reperfusion ; Oxidative stress ; Caspase-3 ; IL-Iβ ; TNF-α ; ICAM-1
- 刊名：Biomedicine & Pharmacotherapy
- 出版年：2016
- 出版时间：December 2016
- 年：2016
- 卷：84
- 期：Complete
- 页码：861-869
- 全文大小：1859 K
- 卷排序：84
文摘
Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3 g/kg) were subjected to bilateral ischemia for 30 min by occlusion of renal pedicles, then reperfused for 6 h. Rats in the vehicle I/R group showed a significant (p ˂ 0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p ˂ 0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5 mg/kg bdwt) and diltiazem (5 mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.