1. bookVolume 51 (2017): Issue 1 (January 2017)
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year
access type Open Access

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

Published Online: 17 Feb 2017
Volume & Issue: Volume 51 (2017) - Issue 1 (January 2017)
Page range: 20 - 30
Journal Details
First Published
30 Mar 2016
Publication timeframe
4 times per year

Objective. The aim of the current study was to assess the protective outcome of hemin, a heme oxygenase-1 (HO-1) inducer on L-arginine-induced acute pancreatitis in rats. Acute pancreatitis (AP) is considered to be a critical inflammatory disorder with a major impact on the patient health. Various theories have been recommended regarding the pathophysiology of AP and associated pulmonary complications.

Methods. Twenty-four adult male albino rats were randomly divided into four groups: control group, acute pancreatitis (AP), hemin pre-treated AP group, and hemin post-treated AP group.

Results. Administration of hemin before induction of AP significantly attenuated the L-arginine- induced pancreatitis and associated pulmonary complications characterized by the increasing serum levels of amylase, lipase, tumor necrosis factor-α, nitric oxide, and histo-architectural changes in pancreas and lungs as compared to control group. Additionally, pre-treatment with hemin significantly compensated the deficits in total antioxidant capacities and lowered the elevated malondialdehyde levels observed with AP. On the other hand, post-hemin administration did not show any protection against L-arginine-induced AP.

Conclusions. The current study indicates that the induction of HO-1 by hemin pre-treatment significantly ameliorated the L-arginine-induced pancreatitis and associated pulmonary complications may be due to its anti-inflammatory and antioxidant properties.


Akbarshahi H, Sam A, Chen C, Rosendahl A, Andersson R. Early activation of pulmonary TGF-β1/Smad2 signaling in mice with acute pancreatitis-associated acute lung injury. Mediators Infl amm 2014, 148029, 2014.10.1155/2014/148029394495824688224Search in Google Scholar

Akyazi I, Eraslan E, Gulcubuk A, Ekiz EE, Cirakli ZL, Haktanir D, Bala DA, Ozkurt M, Matur E, Ozcan M. Longterm aspirin pretreatment in the prevention of cerulein-induced acute pancreatitis in rats. World J Gastroenterol 19, 2894-2903, 2013.10.3748/wjg.v19.i19.2894366081423704822Search in Google Scholar

Al-Kahtani M, Abdel-Moneim A, Elmenshawy O, El-Kersh M. Hemin attenuates cisplatin-induced acute renal injury in male rats. Oxid Med Cell Longev 2014, 476430, 2014.10.1155/2014/476430419012325332751Search in Google Scholar

Al-Malki A. Suppression of acute pancreatitis by L-lysine in mice BMC Complementary and Alternative Medicine. The official journal of the International Society for Complementary Medicine Research (ISCMR) 15, 193, 2015.10.1186/s12906-015-0729-x447608726100532Search in Google Scholar

Attuwaybi B, Kozar R, Moore-Olufemi S, Sato N, Hassoun HT, Weisbrodt NW, Moore FA. Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury. J Surg Res 2004, 53-57, 2004.10.1016/j.jss.2004.01.01015093717Search in Google Scholar

Ben-Amotz R, Bonagura J, Velayutham M, Hamlin R, Burns P, Adin C. Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model. Front Physiol 5, 53, 2014.10.3389/fphys.2014.00053392712324600401Search in Google Scholar

Bharucha A, Kulkarni A, Choi K Camilleri M, Lempke M, Brunn GJ, Gibbons SJ, Zinsmeister AR, Farrugia G. Firstin- human study demonstrating pharmacological activation of heme oxygenase-1 in humans. Clin Pharmacol Th er 87, 187-190, 2010.10.1038/clpt.2009.221290614319956091Search in Google Scholar

Biradar S, Veeresh B. Protective eff ect of lawsone on L-Arginine induced acute pancreatitis in rats. Indian J Exp Biol 51, 256-261, 2013.Search in Google Scholar

Charavaryamath C, Keet T, Aulakh G, Townsend H, Singh B. Lung responses to secondary endotoxin challenge in rats exposed to pig barn air. J Occup Med Toxicol 3, 24, 2008.10.1186/1745-6673-3-24258464318973683Search in Google Scholar

Collino M, Pini A, Mugelli N, Mastroianni R, Bani D, Fantozzi R, Papucci L, Fazi M, Masini E. Benefi cial eff ect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure. Dis Model Mech 6, 1012-1020, 2013.10.1242/dmm.011528370122023592614Search in Google Scholar

Cote A, da Silva R, Cuello A. Current protocols for light microscopy immunocytochemistry. In: Cuello AC, editor. Immunohistochemistry II. Chichester: John Wiley and Sons, pp. 147-168, 1993.Search in Google Scholar

Demirogullari B, Ekingen G, Guz G, Bukan N, Erdem O, Ozen IO, Memis L, Sert S. A comparative study of the eff ects of hemin and bilirubin on bilateral renal ischemia reperfusion injury. Nephron Exp Nephrol 103, e1-e5, 2006.10.1159/00009011316340239Search in Google Scholar

Elder A, Saccone G, Dixon D. Lung injury in acute pancreatitis: mechanisms underlying augmented secondary injury. Pancreatology 12, 49-56, 2012.10.1016/j.pan.2011.12.01222487475Search in Google Scholar

Fortunato F, Deng X, Gates L, McClain CJ, Bimmler D, Graf R, Whitcomb DC. Pancreatic response to endotoxin aft er chronic alcohol exposure: switch from apoptosis to necrosis? Am J Physiol Gastrointest Liver Physiol 290, G232-G241, 2006.10.1152/ajpgi.00040.200515976389Search in Google Scholar

Gulcubuk A1, Sonmez K, Gurel A, Altunatmaz K, Gurler N, Aydin S, Oksuz L, Uzun H, Guzel O. Pathologic alterations detected in acute pancreatitis induced by sodium taurocholate in rats and therapeutic eff ects of curcumin, ciprofl oxacin and metronidazole combination. Pancreatology 5, 345-353, 2005.10.1159/00008653415980663Search in Google Scholar

Habtezion A, Kwan R, Akhtar E, Wanaski SP, Collins SD, Wong RJ, Stevenson DK, Butcher EC, Omary MB. Panhematin provides a therapeutic benefi t in experimental pancreatitis. Gut 60, 671-679, 2011.10.1136/gut.2010.217208358095821159893Search in Google Scholar

Hangaishi M, Ishizaka N, Aizawa T, Kurihara Y, Taguchi J, Nagai R, Kimura S, Ohno M. Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo. Biochem Biophys Res Commun 279, 582-588, 2000.10.1006/bbrc.2000.397311118329Search in Google Scholar

Huan C, Kim D, Ou P, Alfonso A, Stanek A. Mechanisms of interleukin-22’s benefi cial eff ects in acute pancreatitis. World J Pathophysiol 7, 108-116, 2016.10.4291/wjgp.v7.i1.108475317626909233Search in Google Scholar

Husseini M, Wang G, Patrick C, Crookshank JA, MacFarlane AJ, Noel JA, Strom A, Scott FW. Heme oxygenase-1 induction prevents autoimmune diabetes in association with pancreatic recruitment of M2-Like macrophages, mesenchymal cells, and fi brocytes. Endocrinology 156, 3937-3949, 2015.10.1210/en.2015-130426252059Search in Google Scholar

Kambhampati S, Park W, Habtezion A. Pharmacologic therapy for acute pancreatitis. World J Gastroenterol 20, 16868-16880, 2014.10.3748/wjg.v20.i45.16868425855625493000Search in Google Scholar

Lee E, Lee Y, Lee E, Ryu GR, Ko SH, Moon SD, Song KH, Ahn YB. Protective eff ect of heme oxygenase-1 on high glucose-induced pancreatic β-cell injury. Diabetes Metab J 35, 469-479, 2011.10.4093/dmj.2011.35.5.469322102222111038Search in Google Scholar

Liu X, Wang X, Xin H, Wu D, Xin XM, Miao L, Zhang QY, Zhou Y, Liu Q, Zhang Q, Zhu YZ. Induction of heme oxygenase-1 by sodium 9-hydroxyltanshinone IIA sulfonate derivative contributes to inhibit LPS-mediated infl ammatory response in macrophages. Cell Physiol Biochem 36, 1316-1330, 2015.10.1159/00043029926159150Search in Google Scholar

Lu X, Chen-Roetling J, Regan R. Systemic hemin therapy attenuates blood-brain barrier disruption aft er intracerebral hemorrhage. Neurobiol Dis 70, 245-251, 2014.10.1016/j.nbd.2014.06.005422118624952361Search in Google Scholar

Mills C. M1 and M2 macrophages: Oracles of health and disease. Crit Rev Immunol 32, 463-488, 2012.10.1615/CritRevImmunol.v32.i6.10Search in Google Scholar

Nakamichi I, Habtezion A, Zhong B, Contag C, Butcher E, Omary M. Hemin-activated macrophages home to the pancreas and protect from acute pancreatitis via heme oxygenase-1 induction. J Clin Invest 115, 3007-3014, 2005.10.1172/JCI24912125753516239966Search in Google Scholar

Nikolic I, Saksida T, Mangano K, Vujicic M, Stojanovic I, Nicoletti F, Stosic-Grujicic S. Pharmacological application of carbon monoxide ameliorates islet-directed autoimmunity in mice via anti-infl ammatory and anti-apoptotic eff ects. Diabetologia 57, 980-990, 2014.10.1007/s00125-014-3170-724488023Search in Google Scholar

Park J, Lee S, Chung M, Kwon SH, Kim EH, Ko KH, Kwon CI, Hahm KB. Antioxidative phytoceuticals to ameliorate pancreatitis in animal models: an answer from nature. World J Gastroenterol 20, 16570-16581, 2014.10.3748/wjg.v20.i44.16570424820025469025Search in Google Scholar

Pezzilli R. Immunological aspects of acute respiratory distress syndrome in acute pancreatitis. Immunogastroenterology 2, 104-108, 2013.10.7178/ig.39Search in Google Scholar

Salem F, Lokman M, Kassab R. Ameliorative eff ects of watery extracts of boswella serrata and syzygium aromaticum on L-arginine induced acute pancreatitis in rats. World Journal of Pharmaceutical Research 3, 71-87, 2014.Search in Google Scholar

Sowjanya J, Sandhya T, Veeresh B. Ameliorating Eff ect of Eugenol on L-arginine Induced Acute Pancreatitis and Associated Pulmonary Complications in Rats. Pharmacologia 3, 657-664, 2012.10.5567/pharmacologia.2012.657.664Search in Google Scholar

Taye A, Ibrahim B. Activation of renal haeme oxygenase-1 alleviates gentamicin-induced acute nephrotoxicity in rats. J Pharm Pharmacol 65, 995-1004, 2013.10.1111/jphp.1206723738727Search in Google Scholar

Wang X, Qin W, Qiu X, Cao J, Liu D, Sun B. A novel role of exogenous carbonmonoxide on protecting cardiac function and improving survival against sepsisvia mitochondrial energetic metabolism pathway. Int J Biol Sci 10, 777-788, 2014.10.7150/ijbs.9220411519825076854Search in Google Scholar

Wu D, Zeng Y, Fan Y. Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury. Sci Rep 6, 20545, 2016.10.1038/srep20545474079426841848Search in Google Scholar

Xu X, Yang X, Bai Y, Zhao YR, Shi GS, Zhang JG, Zheng YH. Treatment with ginkgo biloba extract protects rats against acute pancreatitis-associated lung injury by modulating alveolar macrophage. Prz Gastroenterol 9, 43-48, 2014.10.5114/pg.2014.40850402784224868298Search in Google Scholar

Xue H, Guo H, Li YC, Hao ZM. Heme oxygenase-1 induction by hemin protects liver cells from ischemia/reperfusion injury in cirrhotic rats. World J Gastroenterol 13, 5384-5390, 2007.10.3748/wjg.v13.i40.5384417133217879412Search in Google Scholar

Yadav B, Greish K. Selective inhibition of hemeoxygenase-1 as a novel therapeutic target for anticancer treatment. J Nanomedic Nanotechnol S4, 005, 2011.10.4172/2157-7439.S4-005Search in Google Scholar

Yao L, Wang P, Chen M, Liu Y, Zhou L, Fang X, Huang Z. Carbon monoxide-releasing molecules attenuate postresuscitation myocardial injury and protect cardiacmitochondrial function by reducing the production of mitochondrial reactive oxygen species in a rat model of cardiac arrest. J Cardiovasc Pharmacol Th er 20, 330-341, 2015.10.1177/107424841455983725420477Search in Google Scholar

Yegin Z, Iyidir O, Demirtas C, Suyani E, Yetkin I, Pasaoglu H, Ilhan C, Sucak GT. Th e interplay among iron metabolism, endothelium and infl ammatory cascade in dysmetabolic disorders. J Endocrinol Invest 38, 333-338, 2015.10.1007/s40618-014-0174-625245337Search in Google Scholar

Yenicerioglu A, Cetinkaya Z, Girgin M, Ustundag B, Ozercan IH, Ayten R, Kanat BH. Eff ects of trimetazidine in acute pancreatitis induced by L-arginine. Can J Surg 56, 175-179, 2013.10.1503/cjs.032811367243023484468Search in Google Scholar

Yildar M, Basbug M, Ozkan O, Cavdar F, Yaman I, Aksit H, Ozyigit MO, Aslan F, Derici H. Th e eff ects of 2-aminoethyl diphenylborinate on L-Arginine induced acute pancreatitis in the rats. Medical Science and Discovery 2, 352-357, 2015.10.17546/msd.34835Search in Google Scholar

Zhang B, Wei X, Cui X, Kobayashi T, Li W. Eff ects of heme oxygenase 1 on brain edema and neurologic outcome aft er cardiopulmonary resuscitation in rats. Anesthesiology 109, 260-268, 2008.10.1097/ALN.0b013e31817f5c2e18648235Search in Google Scholar

Zhong W, Xia Z, Hinrichs D, Rosenbaum JT, Wegmann KW, Meyrowitz J, Zhang Z. Hemin exerts multiple protective mechanisms and attenuates dextran sulfate sodium-induced colitis. J Pediatr Gastroenterol Nutr 50, 132-139, 2010.10.1097/MPG.0b013e3181c6159120081544Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo