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Current Molecular Pharmacology

Editor-in-Chief

ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

Nitric Oxide Modulation as a Potential Molecular Mechanism Underlying the Protective Role of NaHS in Liver Ischemia Reperfusion Injury

Author(s): Salwa A. Ibrahim*, Seham A. Abdel-Gaber, Mohamed A. Ibrahim, Entesar F. Amin, Rehab K. Mohammed and Aly M. Abdelrahman

Volume 15, Issue 4, 2022

Published on: 06 January, 2022

Article ID: e090921196318 Pages: 7

DOI: 10.2174/1874467214666210909154609

Price: $65

Abstract

Background: Liver IR is a frequent clinical complication with high morbidity and mortality. The present study evaluated the possible protective effect of sodium hydrosulfide (NaHS), a H2S donor, in IR-induced hepatic injury and explored the mechanisms of actions of the investigated drug.

Methods: Male albino rats (200-230 g) were divided into the following groups: group 1:Sham-operated non treated rats, group 2: IR non treated rats, group 3: L-NNA + IR rats, group 4: NaHS + IR rats, group 5: L-NNA + NaHS + IR rats. Blood samples were collected for ALT determination. Liver tissue samples were used for the assessment of GPx, catalase, SOD, MDA, total nitrites and TNF- α. Parts from the liver were fixed in 10% formalin solution for histopathological examination and immunohistochemical examination of iNOS, eNOS and caspase-3.

Results: NaHS protected the liver against IR. This hepatoprotection was associated with normalization of antioxidant enzyme activity and decrease in hepatic MDA, TNF-α and expression of caspase- 3 and iNOS.

Conclusion: NaHS is hepatoprotective in IR injury. The hepatoprotective effects of NaHS are associated with antioxidant, anti-inflammatory and antiapoptotic effects. These effects are probably mediated via NO modulation.

Keywords: Ischemia reperfusion injury, sodium hydrosulfide, nitric oxide, hepatic surgery, liver cells, transplantation.

Graphical Abstract
[1]
Cannistrà, M.; Ruggiero, M.; Zullo, A.; Gallelli, G.; Serafini, S.; Maria, M.; Naso, A.; Grande, R.; Serra, R.; Nardo, B. Hepatic ischemia reperfusion injury: A systematic review of literature and the role of current drugs and biomarkers. Int. J. Surg., 2016, 33(Suppl. 1), S57-S70.
[http://dx.doi.org/10.1016/j.ijsu.2016.05.050] [PMID: 27255130]
[2]
Konishi, T.; Lentsch, A.B. Hepatic ischemia/reperfusion: Mechanisms of tissue injury, repair, and regeneration. Gene Expr., 2017, 17(4), 277-287.
[http://dx.doi.org/10.3727/105221617X15042750874156] [PMID: 28893351]
[3]
Clarke, C.N.; Tevar, A.D.; Lentsch, A.B. Hepatic ischemia/reperfusion injury. Molecular pathology of liver diseases; Springer, 2011, pp. 397-410.
[http://dx.doi.org/10.1007/978-1-4419-7107-4_26]
[4]
Pantazi, E.; Bejaoui, M.; Folch-Puy, E.; Adam, R.; Roselló-Catafau, J. Advances in treatment strategies for ischemia reperfusion injury. Exp. Opin. Pharmacother., 2016, 17(2), 169-179.
[http://dx.doi.org/10.1517/14656566.2016.1115015] [PMID: 26745388]
[5]
Xiao, Q.; Ying, J.; Xiang, L.; Zhang, C. The biologic effect of hydrogen sulfide and its function in various diseases. Medicine (Baltimore), 2018, 97(44), e13065.
[http://dx.doi.org/10.1097/MD.0000000000013065] [PMID: 30383685]
[6]
Tripatara, P.; Patel, N.S.; Collino, M.; Gallicchio, M.; Kieswich, J.; Castiglia, S.; Benetti, E.; Stewart, K.N.; Brown, P.A.; Yaqoob, M.M.; Fantozzi, R.; Thiemermann, C. Generation of endogenous hydrogen sulfide by cystathionine gamma-lyase limits renal ischemia/reperfusion injury and dysfunction. Lab. Invest., 2008, 88(10), 1038-1048.
[http://dx.doi.org/10.1038/labinvest.2008.73] [PMID: 18679378]
[7]
Elrod, J.W.; Calvert, J.W.; Morrison, J.; Doeller, J.E.; Kraus, D.W.; Tao, L.; Jiao, X.; Scalia, R.; Kiss, L.; Szabo, C.; Kimura, H.; Chow, C.W.; Lefer, D.J. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc. Natl. Acad. Sci. USA, 2007, 104(39), 15560-15565.
[http://dx.doi.org/10.1073/pnas.0705891104] [PMID: 17878306]
[8]
Qu, K.; Chen, C.P.; Halliwell, B.; Moore, P.K.; Wong, P.T. Hydrogen sulfide is a mediator of cerebral ischemic damage. Stroke, 2006, 37(3), 889-893.
[http://dx.doi.org/10.1161/01.STR.0000204184.34946.41] [PMID: 16439695]
[9]
Du, J.; Wang, Q.; Li, Q.M.; Zhang, B.M.; Xie, K.L.; Wang, G.L. [Alternation of thioredoxin system in postconditioning with hydrogen sulfide against hepatic ischemia-reperfusion injury in rats]. Zhonghua yi xue za zhi, 2012, 92(37), 2607-2610.
[PMID: 23290060]
[10]
Zhang, Q.; Fu, H.; Zhang, H.; Xu, F.; Zou, Z.; Liu, M.; Wang, Q.; Miao, M.; Shi, X. Hydrogen sulfide preconditioning protects rat liver against ischemia/reperfusion injury by activating Akt-GSK-3β signaling and inhibiting mitochondrial permeability transition. PLoS One, 2013, 8(9), e74422.
[http://dx.doi.org/10.1371/journal.pone.0074422] [PMID: 24058562]
[11]
Volarevic, V.; Misirkic, M.; Vucicevic, L.; Paunovic, V.; Simovic Markovic, B.; Stojanovic, M.; Milovanovic, M.; Jakovljevic, V.; Micic, D.; Arsenijevic, N.; Trajkovic, V.; Lukic, M.L. Metformin aggravates immune-mediated liver injury in mice. Arch. Toxicol., 2015, 89(3), 437-450.
[http://dx.doi.org/10.1007/s00204-014-1263-1] [PMID: 24770553]
[12]
Zhang, Y.Q.; Ding, N.; Zeng, Y.F.; Xiang, Y.Y.; Yang, M.W.; Hong, F.F.; Yang, S.L. New progress in roles of nitric oxide during hepatic ischemia reperfusion injury. World J. Gastroenterol., 2017, 23(14), 2505-2510.
[http://dx.doi.org/10.3748/wjg.v23.i14.2505] [PMID: 28465634]
[13]
Oleshchuk, O.; Ivankiv, Y.; Falfushynska, H.; Mudra, A.; Lisnychuk, N. Hepatoprotective effect of melatonin in toxic liver injury in rats. Medicina (Kaunas), 2019, 55(6), E304.
[http://dx.doi.org/10.3390/medicina55060304] [PMID: 31238587]
[14]
Abdel-latif, R.G.; Morsy, M.A.; El-Moselhy, M.A.; Khalifa, M.A. Sildenafil protects against nitric oxide deficiency-related nephrotoxicity in cyclosporine A treated rats. Eur. J. Pharmacol., 2013, 705(1-3), 126-134.
[http://dx.doi.org/10.1016/j.ejphar.2013.02.039] [PMID: 23499693]
[15]
Fouad, A.A.; El-Rehany, M.A.; Maghraby, H.K. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur. J. Pharmacol., 2007, 572(1), 61-68.
[http://dx.doi.org/10.1016/j.ejphar.2007.06.010] [PMID: 17610873]
[16]
Siriussawakul, A.; Zaky, A.; Lang, J.D. Role of nitric oxide in hepatic ischemia-reperfusion injury. World J. Gastroenterol., 2010, 16(48), 6079-6086.
[http://dx.doi.org/10.3748/wjg.v16.i48.6079] [PMID: 21182222]
[17]
Bryan, N.S.; Grisham, M.B. Methods to detect nitric oxide and its metabolites in biological samples. Free Radic. Biol. Med., 2007, 43(5), 645-657.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.026] [PMID: 17664129]
[18]
El-Awdan, S.A.; Abdel-Sala, O.M. Modulation of antipsychotic-induced oxidative stress by selective and non selective COX2 nonsteroidal anti-inflammatory drugs. Pharmacologia., 2012, 3, 222-226.
[http://dx.doi.org/10.5567/pharmacologia.2012.622.626]
[19]
Kiang, J.G.; Krishnan, S.; Lu, X.; Li, Y. Inhibition of inducible nitric-oxide synthase protects human T cells from hypoxia-induced apoptosis. Mol. Pharmacol., 2008, 73(3), 738-747.
[http://dx.doi.org/10.1124/mol.107.041079] [PMID: 18079278]
[20]
Atef, Y.; El-Fayoumi, H.M.; Abdel-Mottaleb, Y.; Mahmoud, M.F. Effect of cardamonin on hepatic ischemia reperfusion induced in rats: Role of nitric oxide. Eur. J. Pharmacol., 2017, 815, 446-453.
[http://dx.doi.org/10.1016/j.ejphar.2017.09.037] [PMID: 28966130]
[21]
Liu, P.; Yin, K.; Nagele, R.; Wong, P.Y. Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats. J. Pharmacol. Exp. Ther., 1998, 284(3), 1139-1146.
[PMID: 9495876]
[22]
Peralta, C.; Rull, R.; Rimola, A.; Deulofeu, R.; Roselló-Catafau, J.; Gelpí, E.; Rodés, J. Endogenous nitric oxide and exogenous nitric oxide supplementation in hepatic ischemia-reperfusion injury in the rat. Transplantation, 2001, 71(4), 529-536.
[http://dx.doi.org/10.1097/00007890-200102270-00008] [PMID: 11258432]
[23]
Kang, K.; Zhao, M.; Jiang, H.; Tan, G.; Pan, S.; Sun, X. Role of hydrogen sulfide in hepatic ischemia-reperfusion-induced injury in rats. Liver Transpl., 2009, 15(10), 1306-1314.
[http://dx.doi.org/10.1002/lt.21810] [PMID: 19790158]
[24]
Shimada, S.; Fukai, M.; Wakayama, K.; Ishikawa, T.; Kobayashi, N.; Kimura, T.; Yamashita, K.; Kamiyama, T.; Shimamura, T.; Taketomi, A.; Todo, S. Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver. Surg. Today, 2015, 45(7), 892-903.
[http://dx.doi.org/10.1007/s00595-014-1064-4] [PMID: 25362520]
[25]
Bos, E.M.; Snijder, P.M.; Jekel, H.; Weij, M.; Leemans, J.C.; van Dijk, M.C.; Hillebrands, J.L.; Lisman, T.; van Goor, H.; Leuvenink, H.G. Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury. Transpl. Int., 2012, 25(8), 897-908.
[http://dx.doi.org/10.1111/j.1432-2277.2012.01514.x] [PMID: 22716165]
[26]
Xie, Z.Z.; Shi, M.M.; Xie, L.; Wu, Z.Y.; Li, G.; Hua, F.; Bian, J.S. Sulfhydration of p66Shc at cysteine59 mediates the antioxidant effect of hydrogen sulfide. Antioxid. Redox Signal., 2014, 21(18), 2531-2542.
[http://dx.doi.org/10.1089/ars.2013.5604] [PMID: 24766279]
[27]
Wallace, J.L.; Blackler, R.W.; Chan, M.V.; Da Silva, G.J.; Elsheikh, W.; Flannigan, K.L.; Gamaniek, I.; Manko, A.; Wang, L.; Motta, J.P.; Buret, A.G. Anti-inflammatory and cytoprotective actions of hydrogen sulfide: Translation to therapeutics. Antioxid. redox signal., 2015, 22(5), 398-410.
[http://dx.doi.org/10.1089/ars.2014.5901] [PMID: 24635322]
[28]
Wang, R. Two’s company, three’s a crowd: Can H2S be the third endogenous gaseous transmitter? FASEB J., 2002, 16(13), 1792-1798.
[http://dx.doi.org/10.1096/fj.02-0211hyp] [PMID: 12409322]
[29]
Zhao, W.; Wang, R. H(2)S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am. J. physiol. heart circ. physiol., 2002, 283(2), H474-H480.
[http://dx.doi.org/10.1152/ajpheart.00013.2002] [PMID: 12124191]
[30]
Li, L.; Bhatia, M.; Zhu, Y.Z.; Zhu, Y.C.; Ramnath, R.D.; Wang, Z.J.; Anuar, F.B.; Whiteman, M.; Salto-Tellez, M.; Moore, P.K. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J., 2005, 19(9), 1196-1198.
[http://dx.doi.org/10.1096/fj.04-3583fje] [PMID: 15863703]
[31]
Chunyu, Z.; Junbao, D.; Dingfang, B.; Hui, Y.; Xiuying, T.; Chaoshu, T. The regulatory effect of hydrogen sulfide on hypoxic pulmonary hypertension in rats. Biochem. Biophys. Res. Commun., 2003, 302(4), 810-816.
[http://dx.doi.org/10.1016/S0006-291X(03)00256-0] [PMID: 12646242]
[32]
Pan, T.T.; Feng, Z.N.; Lee, S.W.; Moore, P.K.; Bian, J.S. Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes. J. Mol. Cell. Cardiol., 2006, 40(1), 119-130.
[http://dx.doi.org/10.1016/j.yjmcc.2005.10.003] [PMID: 16325198]
[33]
Predmore, B.L.; Kondo, K.; Bhushan, S.; Zlatopolsky, M.A.; King, A.L.; Aragon, J.P.; Grinsfelder, D.B.; Condit, M.E.; Lefer, D.J. The polysulfide diallyl trisulfide protects the ischemic myocardium by preservation of endogenous hydrogen sulfide and increasing nitric oxide bioavailability. Am. J. Physiol. Hart Circ. Physiol., 2012, 302(11), H2410-H2418.
[http://dx.doi.org/10.1152/ajpheart.00044.2012] [PMID: 22467307]
[34]
King, A.L.; Polhemus, D.J.; Bhushan, S.; Otsuka, H.; Kondo, K.; Nicholson, C.K.; Bradley, J.M.; Islam, K.N.; Calvert, J.W.; Tao, Y.X.; Dugas, T.R.; Kelley, E.E.; Elrod, J.W.; Huang, P.L.; Wang, R.; Lefer, D.J. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent. Proc. Natl. Acad. Sci. USA, 2014, 111(8), 3182-3187.
[http://dx.doi.org/10.1073/pnas.1321871111] [PMID: 24516168]

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