Open Access

Carbon monoxide releasing molecule‑2 (CORM‑2)‑liberated CO ameliorates acute pancreatitis

  • Authors:
    • Yishu Liu
    • Xu Wang
    • Xiaohan Xu
    • Weiting Qin
    • Bingwei Sun
  • View Affiliations

  • Published online on: April 19, 2019     https://doi.org/10.3892/mmr.2019.10173
  • Pages: 5142-5152
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The purpose of the present study was to investigate the effect of carbon monoxide (CO) released from CO‑releasing molecule 2 (CORM‑2) on mice with acute pancreatitis (AP). To perform the investigation, a mouse AP model was established using caerulein. The mice were treated with or without CORM‑2. The survival rate of the mice in the different groups was analyzed, and serum amylase and lipase levels were measured to assess the degree of pancreatic injury. The severity of AP was also evaluated by histological examination, and histopathological scoring of the pancreatic damage was performed. Pancreatic cell apoptosis was analyzed using a terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labelling assay. The function of the lung and liver was also assessed in the present study. Furthermore, the role of CORM‑2 on oxidative stress, intercellular adhesion molecule 1 (ICAM‑1) and vascular cell adhesion molecule 1 (VCAM‑1) expression, pro‑inflammatory cytokine production, and nuclear factor (NF)‑κB activation in the pancreas of AP mice was determined. The results demonstrated that CORM‑2 reduced the mortality, pancreatic damage, and lung and liver injury of AP mice. CORM‑2 administration also reduced systemic and localized inflammatory cell factors. Furthermore, treatment with CORM‑2 inhibited the expression of ICAM‑1 and VCAM‑1, and the activation of NF‑κB and phosphorylated inhibitor of NF‑κB subunit α, in the pancreas of AP mice. These results indicated that CO released from CORM‑2 exerted protective effects on AP mice, and the beneficial effects were likely due to inhibition of NF‑κB pathway activation.

References

1 

Yadav D and Lowenfels AB: Trends in the epidemiology of the first attack of acute pancreatitis: A systematic review. Pancreas. 33:323–330. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Ohashi S, Nishio A, Nakamura H, Kido M, Ueno S, Uza N, Inoue S, Kitamura H, Kiriya K, Asada M, et al: Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 290:G772–G781. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Bhatia M, Ramnath RD, Chevali L and Guglielmotti A: Treatment with bindarit, a blocker of MCP-1 synthesis, protects mice against acute pancreatitis. Am J Physiol Gastrointest Liver Physiol. 288:G1259–G1265. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Cuzzocrea S, Genovese T, Mazzon E, Di Paola R, Muià C, Britti D and Salvemini D: Reduction in the development of cerulein-induced acute pancreatitis by treatment with M40401, a new selective superoxide dismutase mimetic. Shock. 22:254–261. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Escobar J, Pereda J, Arduini A, Sandoval J, Sabater L, Aparisi L, López-Rodas G and Sastre J: Cross-talk between oxidative stress and pro-inflammatory cytokines in acute pancreatitis: A key role for protein phosphatases. Curr Pharm Des. 15:3027–3042. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Zhou HX, Han B, Hou LM, An TT, Jia G, Cheng ZX, Ma Y, Zhou YN, Kong R, Wang SJ, et al: Protective effects of hydrogen gas on experimental acute pancreatitis. PLoS One. 11:e01544832016. View Article : Google Scholar : PubMed/NCBI

7 

Pereda J, Escobar J, Sandoval J, Rodríguez JL, Sabater L, Pallardó FV, Torres L, Franco L, Viña J, López-Rodas G and Sastre J: Glutamate cysteine ligase up-regulation fails in necrotizing pancreatitis. Free Radic Biol Med. 44:1599–1609. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Gómez-Cambronero LG, Sabater L, Pereda J, Cassinello N, Camps B, Viña J and Sastre J: Role of cytokines and oxidative stress in the pathophysiology of acute pancreatitis: therapeutical implications. Curr Drug Targets Inflamm Allergy. 1:393–403. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Altavilla D, Famulari C, Passaniti M, Galeano M, Macrì A, Seminara P, Minutoli L, Marini H, Calò M, Venuti FS, et al: Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice. Lab Invest. 83:1723–1732. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Yu JH, Lim JW, Namkung W, Kim H and Kim KH: Suppression of cerulein-induced cytokine expression by antioxidants in pancreatic acinar cells. Lab Invest. 82:1359–1368. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Pereda J, Sabater L, Aparisi L, Escobar J, Sandoval J, Viña J, López-Rodas G and Sastre J: Interaction between cytokines and oxidative stress in acute pancreatitis. Curr Med Chem. 13:2775–2787. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Frossard JL, Hadengue A, Spahr L, Morel P and Pastor CM: Natural history of long-term lung injury in mouse experimental pancreatitis. Crit Care Med. 30:1541–1546. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Bak I, Szendrei L, Turoczi T, Papp G, Joo F, Das DK, de Leiris J, Der P, Juhasz B, Varga E, et al: Heme oxygenase-1-related carbon monoxide production and ventricular fibrillation in isolated ischemic/reperfused mouse myocardium. FASEB J. 17:2133–2135. 2003. View Article : Google Scholar : PubMed/NCBI

14 

Song H, Zhao H, Qu Y, Sun Q, Zhang F, Du Z, Liang W, Qi Y and Yang P: Carbon monoxide releasing molecule-3 inhibits concurrent tumor necrosis factor-α- and interleukin-1β-induced expression of adhesion molecules on human gingival fibroblasts. J Periodontal Res. 46:48–57. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Patterson EK, Fraser DD, Capretta A, Potter RF and Cepinskas G: Carbon monoxide-releasing molecule 3 inhibits myeloperoxidase (MPO) and protects against MPO-induced vascular endothelial cell activation/dysfunction. Free Radic Biol Med. 70:167–173. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Zheng M, Zhang Q, Joe Y, Kim SK, Uddin MJ, Rhew H, Kim T, Ryter SW and Chung HT: Carbon monoxide-releasing molecules reverse leptin resistance induced by endoplasmic reticulum stress. Am J Physiol Endocrinol Metab. 304:E780–E788. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Lee TS and Chau LY: Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med. 8:240–246. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Motterlini R, Mann BE, Johnson TR, Clark JE, Foresti R and Green CJ: Bioactivity and pharmacological actions of carbon monoxide-releasing molecules. Curr Pharm Des. 9:2525–2539. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Seixas JD, Santos MF, Mukhopadhyay A, Coelho AC, Reis PM, Veiros LF, Marques AR, Penacho N, Gonçalves AM, Romão MJ, et al: A contribution to the rational design of Ru(CO)3Cl2L complexes for in vivo delivery of CO. Dalton Trans. 44:5058–5075. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE and Green CJ: Carbon monoxide-releasing molecules: Characterization of biochemical and vascular activities. Circ Res. 90:E17–E24. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Chung SW, Liu X, Macias AA, Baron RM and Perrella MA: Heme oxygenase-1-derived carbon monoxide enhances the host defense response to microbial sepsis in mice. J Clin Invest. 118:239–247. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Sun B, Sun Z, Jin Q and Chen X: CO-releasing molecules (CORM-2)-liberated CO attenuates leukocytes infiltration in the renal tissue of thermally injured mice. Int J Biol Sci. 4:176–183. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Lee S, Lee SJ, Coronata AA, Fredenburgh LE, Chung SW, Perrella MA, Nakahira K, Ryter SW and Choi AM: Carbon monoxide confers protection in sepsis by enhancing beclin 1-dependent autophagy and phagocytosis. Antioxid Redox Signal. 20:432–442. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Wang X, Qin W, Qiu X, Cao J, Liu D and Sun B: A novel role of exogenous carbon monoxide on protecting cardiac function and improving survival against sepsis via mitochondrial energetic metabolism pathway. Int J Biol Sci. 10:777–788. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Pastor CM, Pugin J, Kwak B, Chanson M, Mach F, Hadengue A and Frossard JL: Role of Toll-like receptor 4 on pancreatic and pulmonary injury in a mice model of acute pancreatitis associated with endotoxemia. Crit Care Med. 32:1759–1763. 2004. View Article : Google Scholar : PubMed/NCBI

26 

Bhatia M, Slavin J, Cao Y, Basbaum AI and Neoptolemos JP: Preprotachykinin-a gene deletion protects mice against acute pancreatitis and associated lung injury. Am J Physiol Gastrointest Liver Physiol. 284:G830–G836. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Sharif R, Dawra R, Wasiluk K, Phillips P, Dudeja V, Kurt-Jones E, Finberg R and Saluja A: Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice. Gut. 58:813–819. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Shen WC, Wang X, Qin WT, Qiu XF and Sun BW: Exogenous carbon monoxide suppresses Escherichia coli vitality and improves survival in an Escherichia coli-induced murine sepsis model. Acta Pharmacol Sin. 35:1566–1576. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Liu DM, Sun BW, Sun ZW, Jin Q, Sun Y and Chen X: Suppression of inflammatory cytokine production and oxidative stress by CO-releasing molecules-liberated CO in the small intestine of thermally-injured mice. Acta Pharmacol Sin. 29:838–846. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Sun BW, Jin Q, Sun Y, Sun ZW, Chen X, Chen ZY and Cepinskas G: Carbon liberated from CO-releasing molecules attenuates leukocyte infiltration in the small intestine of thermally injured mice. World J Gastroenterol. 13:6183–6190. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Deng W, Hui Y, Yu J, Wang W, Xu S, Chen C and Xiong X: A new pathological scoring method for adrenal injury in rats with severe acute pancreatitis. Pathol Res Pract. 210:1011–1017. 2014. View Article : Google Scholar : PubMed/NCBI

32 

Barker PM, Nguyen MS, Gatzy JT, Grubb B, Norman H, Hummler E, Rossier B, Boucher RC and Koller B: Role of gammaENaC subunit in lung liquid clearance and electrolyte balance in newborn mice. Insights into perinatal adaptation and pseudohypoaldosteronism. J Clin Invest. 102:1634–1640. 1998. View Article : Google Scholar : PubMed/NCBI

33 

Hillegass LM, Griswold DE, Brickson B and Albrightson-Winslow C: Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods. 24:285–295. 1990. View Article : Google Scholar : PubMed/NCBI

34 

Wang J, Chen G, Gong H, Huang W, Long D and Tang W: Amelioration of experimental acute pancreatitis with dachengqi decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell. PLoS One. 7:e401602012. View Article : Google Scholar : PubMed/NCBI

35 

Bang S, Kang YH, Reynolds C and Kang M: The pan-Bcl-2 family inhibitor ABT-737 synergizes with DNA damaging agents by enhancing apoptosis in acute lymphoblastic leukemia cells. Cancer Research. 69:2009.

36 

Funaro A, Ortolan E, Ferranti B, Gargiulo L, Notaro R, Luzzatto L and Malavasi F: CD157 is an important mediator of neutrophil adhesion and migration. Blood. 104:4269–4278. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Dawra R, Ku YS, Sharif R, Dhaulakhandi D, Phillips P, Dudeja V and Saluja AK: An improved method for extracting myeloperoxidase and determining its activity in the pancreas and lungs during pancreatitis. Pancreas. 37:62–68. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Armbruster C and Kriwanek S: Multicentre audit of death from acute pancreatitis. Br J Surg. 81:16971994. View Article : Google Scholar : PubMed/NCBI

39 

Chen P, Sun B, Chen H, Wang G, Pan S, Kong R, Bai X and Wang S: Effects of carbon monoxide releasing molecule-liberated CO on severe acute pancreatitis in rats. Cytokine. 49:15–23. 2010. View Article : Google Scholar : PubMed/NCBI

40 

Rae D, Bowyer RC and Wharton RQ: Inflammatory mediators in acute pancreatitis. Br J Surg. 82:8551995. View Article : Google Scholar : PubMed/NCBI

41 

de Beaux AC, Goldie AS, Ross JA, Carter DC and Fearon KC: Serum concentrations of inflammatory mediators related to organ failure in patients with acute pancreatitis. Br J Surg. 83:349–353. 1996. View Article : Google Scholar : PubMed/NCBI

42 

Wang X, Qin W, Song M, Zhang Y and Sun B: Exogenous carbon monoxide inhibits neutrophil infiltration in LPS-induced sepsis by interfering with FPR1 via p38 MAPK but not GRK2. Oncotarget. 7:34250–34265. 2016.PubMed/NCBI

43 

Sun BW, Zhang P, Zou XQ, Shi GS and Sun Y: Inhibitive effect of exogenous carbon monoxide-releasing molecules 2 on the activation of Janus kinase/signal transducer and activator of transcription pathway in sepsis. Zhonghua Shao Shang Za Zhi. 26:100–103. 2010.(In Chinese). PubMed/NCBI

44 

Sun BW, Shi GS, Zhang P, Zou XQ and Chen X: Inhibitive effect of exogenous carbon monoxide-releasing molecules 2 on tissue factor expression in sepsis. Zhonghua Shao Shang Za Zhi. 25:111–114. 2009.(In Chinese). PubMed/NCBI

45 

Xue J and Habtezion A: Carbon monoxide-based therapy ameliorates acute pancreatitis via TLR4 inhibition. J Clin Invest. 124:437–447. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Kim GY, Roh SI, Park SK, Ahn SC, Oh YH, Lee JD and Park YM: Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom Phellinus linteus. Biol Pharm Bull. 26:1418–1423. 2003. View Article : Google Scholar : PubMed/NCBI

47 

Bettaieb A, Chahed S, Tabet G, Yang J, Morisseau C, Griffey S, Hammock BD and Haj FG: Effects of soluble epoxide hydrolase deficiency on acute pancreatitis in mice. PLoS One. 9:e1130192014. View Article : Google Scholar : PubMed/NCBI

48 

Yin MJ, Yamamoto Y and Gaynor RB: The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 396:77–80. 1998. View Article : Google Scholar : PubMed/NCBI

49 

Sun B, Zou X, Chen Y, Zhang P and Shi G: Preconditioning of carbon monoxide releasing molecule-derived CO attenuates LPS-induced activation of HUVEC. Int J Biol Sci. 4:270–278. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Dolinay T, Szilasi M, Liu M and Choi AM: Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury. Am J Respir Crit Care Med. 170:613–620. 2004. View Article : Google Scholar : PubMed/NCBI

51 

Motterlini R and Otterbein LE: The therapeutic potential of carbon monoxide. Nat Rev Drug Discov. 9:728–743. 2010. View Article : Google Scholar : PubMed/NCBI

52 

Tzeng E: Carbon monoxide: Vascular therapeutic for the future. Vascular. 17 (Suppl 1):S55–S62. 2009. View Article : Google Scholar : PubMed/NCBI

53 

Thom SR, Weaver LK and Hampson NB: Therapeutic carbon monoxide may be toxic. Am J Respir Crit Care Med. 171:13182005. View Article : Google Scholar : PubMed/NCBI

54 

Desmard M, Foresti R, Morin D, Dagouassat M, Berdeaux A, Denamur E, Crook SH, Mann BE, Scapens D, Montravers P, et al: Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules. Antioxid Redox Signal. 16:53–63. 2012. View Article : Google Scholar

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June 2019
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Copy and paste a formatted citation
APA
Liu, Y., Wang, X., Xu, X., Qin, W., & Sun, B. (2019). Carbon monoxide releasing molecule‑2 (CORM‑2)‑liberated CO ameliorates acute pancreatitis. Molecular Medicine Reports, 19, 5142-5152. https://doi.org/10.3892/mmr.2019.10173
MLA
Liu, Y., Wang, X., Xu, X., Qin, W., Sun, B."Carbon monoxide releasing molecule‑2 (CORM‑2)‑liberated CO ameliorates acute pancreatitis". Molecular Medicine Reports 19.6 (2019): 5142-5152.
Chicago
Liu, Y., Wang, X., Xu, X., Qin, W., Sun, B."Carbon monoxide releasing molecule‑2 (CORM‑2)‑liberated CO ameliorates acute pancreatitis". Molecular Medicine Reports 19, no. 6 (2019): 5142-5152. https://doi.org/10.3892/mmr.2019.10173