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Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury.
Eur J Pharmacol. 2014 Oct 15; 741:64-73.EJ

Abstract

Ischemia-reperfusion injury (IRI) is an important cause of liver damage in many clinical situations. Levosimendan is a promising therapy for prevention of IRI. The present work investigated the possible contribution of nitric oxide (NO), cyclooxygenase (COX) enzymes, and adenosine triphosphate sensitive potassium channel (K-ATP) in the protective effect of levosimendan in liver IRI in rats. Rats were divided into 7 groups. Sham-operated group (negative control group); IR-nontreated group (positive control group), levosimendan-treated group (treated with levosimendan); indomethacin, nonselective COX inhibitor,+levosimendan group (cotreated with indomethacin+levosimendan); celecoxib (selective COX-2 inhibitor)+levosimendan group; L-NNA (Nitro- ω-L-arginine, nonselective NO synthase inhibitor)+levosimendan group; and glibenclamide (K-ATP blocker)+levosimendan group. Liver injury was evaluated biochemically (by serum level of alanine aminotransferase (ALT)) as well as by histopathology. Hepatic tissue content of oxidative stress markers, tumor necrosis factor-alpha (TNF-α), along with immunohistochemical expression of induced NO synthase (iNOS), endothelial NO synthase (eNOS), and caspase-3 in hepatic tissue were assayed. The study showed that levosimendan attenuated liver IRI as evidenced by a decrease in serum ALT level and confirmed by histopathology. The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-α, iNOS, eNOS, and caspase-3. The hepatoprotective effect of levosimendan was partially attenuated by pretreatment by either nonselective COX inhibitor, NOS inhibitor, or K-ATP channel blocker; indicating that the hepatoprotective effect of levosimendan was attributed, at least in part to activation of COX-1, modulation of NO, and opening of K-ATP channel.

Authors+Show Affiliations

Departments of Pharmacology, Faculty of medicine, Minia University, El-Minia, Egypt. Electronic address: maim69@yahoo.com.Departments of Pharmacology, Faculty of medicine, Minia University, El-Minia, Egypt.Departments of Pharmacology, Faculty of medicine, Minia University, El-Minia, Egypt.Departments of Pharmacology, Faculty of medicine, Minia University, El-Minia, Egypt.Departments of Pathology, Faculty of medicine, Minia University, Egypt.Departments of Pharmacology, Faculty of medicine, Minia University, El-Minia, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25094034

Citation

Ibrahim, Mohamed A., et al. "Molecular Mechanisms Contributing to the Protective Effect of Levosimendan in Liver Ischemia-reperfusion Injury." European Journal of Pharmacology, vol. 741, 2014, pp. 64-73.
Ibrahim MA, Abdel-Gaber SA, Amin EF, et al. Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. Eur J Pharmacol. 2014;741:64-73.
Ibrahim, M. A., Abdel-Gaber, S. A., Amin, E. F., Ibrahim, S. A., Mohammed, R. K., & Abdelrahman, A. M. (2014). Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. European Journal of Pharmacology, 741, 64-73. https://doi.org/10.1016/j.ejphar.2014.07.047
Ibrahim MA, et al. Molecular Mechanisms Contributing to the Protective Effect of Levosimendan in Liver Ischemia-reperfusion Injury. Eur J Pharmacol. 2014 Oct 15;741:64-73. PubMed PMID: 25094034.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. AU - Ibrahim,Mohamed A, AU - Abdel-Gaber,Seham A, AU - Amin,Entesar F, AU - Ibrahim,Salwa A, AU - Mohammed,Rehab K, AU - Abdelrahman,Aly M, Y1 - 2014/08/02/ PY - 2014/05/17/received PY - 2014/07/12/revised PY - 2014/07/19/accepted PY - 2014/8/6/entrez PY - 2014/8/6/pubmed PY - 2015/6/24/medline KW - Liver ischemia-reperfusion injury KW - levosimendan SP - 64 EP - 73 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 741 N2 - Ischemia-reperfusion injury (IRI) is an important cause of liver damage in many clinical situations. Levosimendan is a promising therapy for prevention of IRI. The present work investigated the possible contribution of nitric oxide (NO), cyclooxygenase (COX) enzymes, and adenosine triphosphate sensitive potassium channel (K-ATP) in the protective effect of levosimendan in liver IRI in rats. Rats were divided into 7 groups. Sham-operated group (negative control group); IR-nontreated group (positive control group), levosimendan-treated group (treated with levosimendan); indomethacin, nonselective COX inhibitor,+levosimendan group (cotreated with indomethacin+levosimendan); celecoxib (selective COX-2 inhibitor)+levosimendan group; L-NNA (Nitro- ω-L-arginine, nonselective NO synthase inhibitor)+levosimendan group; and glibenclamide (K-ATP blocker)+levosimendan group. Liver injury was evaluated biochemically (by serum level of alanine aminotransferase (ALT)) as well as by histopathology. Hepatic tissue content of oxidative stress markers, tumor necrosis factor-alpha (TNF-α), along with immunohistochemical expression of induced NO synthase (iNOS), endothelial NO synthase (eNOS), and caspase-3 in hepatic tissue were assayed. The study showed that levosimendan attenuated liver IRI as evidenced by a decrease in serum ALT level and confirmed by histopathology. The protective effect of levosimendan was associated with modulation of oxidative stress, TNF-α, iNOS, eNOS, and caspase-3. The hepatoprotective effect of levosimendan was partially attenuated by pretreatment by either nonselective COX inhibitor, NOS inhibitor, or K-ATP channel blocker; indicating that the hepatoprotective effect of levosimendan was attributed, at least in part to activation of COX-1, modulation of NO, and opening of K-ATP channel. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/25094034/Molecular_mechanisms_contributing_to_the_protective_effect_of_levosimendan_in_liver_ischemia_reperfusion_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00586-X DB - PRIME DP - Unbound Medicine ER -