Protective effect of apocynin on lung injury induced by acute necrotic pancreatitis in rat_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIA He ¹ , YANG Xiaojia ^1,2 , HONG Yupu ^1,2 , MEI Fangchao ^1,2 ,  WANG Weixing ¹

1. Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Key Laboratory of Hubei Province for Digestive System Disease, Wuhan 430060, P. R. China;

Corresponding author：

WANG Weixing, Email: sate.llite@163.com

Keywords：

acute necrotic pancreatitis; NADPH oxidase Ⅱ; lung injury

DOI：

10.7507/1007-9424.201804017

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate protective effect of apocynin, the inhibitor of NADPH oxidase Ⅱ (NOX2), on lung injury induced by acute necrotic pancreatitis (ANP) in rat. Methods Forty SPF adult male Wistar rats were randomly divided into 4 groups: shame operation group (SO group, n=10), ANP model group (ANP group, n=12), apocynin treated group (APO group, n=10), and apocynin control group (APO-CON group, n=8). The ANP models were induced by the retrograde injection of 5% sodium taurocholate through the biliopancreatic duct in the ANP group and the APO group. The apocynin was injected at 30 min before the induction of ANP models in the APO group. The pancreas and duodenum of rats were just flipped and the apocynin and the 10% DMSO (2 mL/kg) were injected in the APO-CON group and SO group respectively. All the rats were sacrificed at 12 h after the operation. The blood samples were collected by the inferior vena cava puncture, and the levels of serum amylase and lipase were measured by the auto-chemistry analyzer. The lung tissues were harvested and the integrated optical densities (IODs) of the nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and NOX2 were detected by the immunohistochemistry assay. The IODs of the myeloperoxidase (MPO), Toll like receptor 4 (TLR4), and CD68 were detected by the immunofluorescence assay. The concentration of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) were tested by the ELISA method. Results The levels of the serum amylase and lipase and the IODs of the NF-κB, TNF-α, NOX2, MPO, TLR4, CD68, and concentration of MDA of the lung tissues in the ANP group were significantly increased as compared with the SO group (P<0.05), these indices in the APO group were significantly decreased as compared with the ANP group (P<0.05). The SOD activity of the lung tissue in the ANP group was significantly decreased as compared with the SO group (P<0.05), which in the APO group was significantly increased as compared with the ANP group (P<0.05). Conclusion Apocynin can ameliorate lung injury induced by ANP through inhibiting activity of NOX2.

Citation： XIA He, YANG Xiaojia, HONG Yupu, MEI Fangchao, WANG Weixing. Protective effect of apocynin on lung injury induced by acute necrotic pancreatitis in rat. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2018, 25(10): 1165-1170. doi: 10.7507/1007-9424.201804017 Copy

1.	Manohar M, Verma AK, Venkateshaiah SU, et al. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther, 2017, 8(1): 10-25.
2.	Zhang H, Neuhöfer P, Song L, et al. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. J Clin Invest, 2013, 123(3): 1019-1031.
3.	Halonen KI, Pettilä V, Leppäniemi AK, et al. Multiple organ dysfunction associated with severe acute pancreatitis. Crit Care Med, 2002, 30(6): 1274-1279.
4.	Mole DJ, Webster SP, Uings I, et al. Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis. Nat Med, 2016, 22(2): 202-209.
5.	Bernard K, Hecker L, Luckhardt TR, et al. NADPH oxidases in lung health and disease. Antioxid Redox Signal, 2014, 20(17): 2838-2853.
6.	古升, 陈家诚, 周贞学, 等. 胰淀粉酶水平变化与急性胰腺炎病情严重程度的相关性分析. 中国临床研究, 2016, 29(5): 629-631.
7.	Pavlidis P, Crichton S, Lemmich Smith J, et al. Improved outcome of severe acute pancreatitis in the intensive care unit. Crit Care Res Pract, 2013, 2013: 897107.
8.	Chen C, Xu S, Wang WX, et al. Rosiglitazone attenuates the severity of sodium taurocholate-induced acute pancreatitis and pancreatitis-associated lung injury. Arch Med Res, 2009, 40(2): 79-88.
9.	Cheng G, Cao Z, Xu X, et al. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene, 2001, 269(1-2): 131-140.
10.	Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol, 2004, 4(3): 181-189.
11.	Suh YA, Arnold RS, Lassegue B, et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature, 1999, 401(6748): 79-82.
12.	Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev, 2007, 87(1): 245-313.
13.	Liu PG, He SQ, Zhang YH, et al. Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice. World J Gastroenterol, 2008, 14(18): 2832-2837.
14.	Barnes MA, McMullen MR, Roychowdhury S, et al. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology, 2013, 57(5): 1980-1991.
15.	Windyga J, Stefanska-Windyga E, Odnoczko E, et al. Activated prothrombin complex concentrate in combination with tranexamic acid: a single centre experience for the treatment of mucosal bleeding and dental extraction in haemophilia patients with inhibitors. Haemophilia, 2016, 22(5): e465-e468.
16.	Whitmore LC, Goss KL, Newell EA, et al. NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome. Am J Physiol Lung Cell Mol Physiol, 2014, 307(1): L71-L82.
17.	Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Surgery, 2000, 128(2): 225-231.
18.	Lv W, Lv C, Yu S, et al. Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury. Exp Biol Med (Maywood), 2013, 238(12): 1388-1395.
19.	Dasari MS, Richards KM, Alt ML, et al. Synthesis of diapocynin. J Chem Educ, 2008, 85(3): 411-412.
20.	Yubero S, Ramudo L, Manso MA, et al. Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis. Biochim Biophys Acta, 2009, 1792(12): 1205-1211.
21.	Kim C, Sano Y, Todorova K, et al. The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. Nat Immunol, 2008, 9(9): 1019-1027.
22.	Deng W, Abliz A, Xu S, et al. Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin. Mol Med Rep, 2016, 14(4): 3525-3534.
23.	Hayyan M, Hashim MA, AlNashef IM. Superoxide ion: generation and chemical implications. Chem Rev, 2016, 116(5): 3029-3085.
24.	Kim JM, Kim HK, Im YN, et al. FcγR/ROS/CK2α is the key inducer of NF-κB activation in a murine model of asthma. Int Arch Allergy Immunol, 2018, 175(1-2): 16-25.
25.	Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol, 2014, 5: 316.

1. Manohar M, Verma AK, Venkateshaiah SU, et al. Pathogenic mechanisms of pancreatitis. World J Gastrointest Pharmacol Ther, 2017, 8(1): 10-25.
2. Zhang H, Neuhöfer P, Song L, et al. IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality. J Clin Invest, 2013, 123(3): 1019-1031.
3. Halonen KI, Pettilä V, Leppäniemi AK, et al. Multiple organ dysfunction associated with severe acute pancreatitis. Crit Care Med, 2002, 30(6): 1274-1279.
4. Mole DJ, Webster SP, Uings I, et al. Kynurenine-3-monooxygenase inhibition prevents multiple organ failure in rodent models of acute pancreatitis. Nat Med, 2016, 22(2): 202-209.
5. Bernard K, Hecker L, Luckhardt TR, et al. NADPH oxidases in lung health and disease. Antioxid Redox Signal, 2014, 20(17): 2838-2853.
6. 古升, 陈家诚, 周贞学, 等. 胰淀粉酶水平变化与急性胰腺炎病情严重程度的相关性分析. 中国临床研究, 2016, 29(5): 629-631.
7. Pavlidis P, Crichton S, Lemmich Smith J, et al. Improved outcome of severe acute pancreatitis in the intensive care unit. Crit Care Res Pract, 2013, 2013: 897107.
8. Chen C, Xu S, Wang WX, et al. Rosiglitazone attenuates the severity of sodium taurocholate-induced acute pancreatitis and pancreatitis-associated lung injury. Arch Med Res, 2009, 40(2): 79-88.
9. Cheng G, Cao Z, Xu X, et al. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene, 2001, 269(1-2): 131-140.
10. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol, 2004, 4(3): 181-189.
11. Suh YA, Arnold RS, Lassegue B, et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature, 1999, 401(6748): 79-82.
12. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev, 2007, 87(1): 245-313.
13. Liu PG, He SQ, Zhang YH, et al. Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice. World J Gastroenterol, 2008, 14(18): 2832-2837.
14. Barnes MA, McMullen MR, Roychowdhury S, et al. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology, 2013, 57(5): 1980-1991.
15. Windyga J, Stefanska-Windyga E, Odnoczko E, et al. Activated prothrombin complex concentrate in combination with tranexamic acid: a single centre experience for the treatment of mucosal bleeding and dental extraction in haemophilia patients with inhibitors. Haemophilia, 2016, 22(5): e465-e468.
16. Whitmore LC, Goss KL, Newell EA, et al. NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome. Am J Physiol Lung Cell Mol Physiol, 2014, 307(1): L71-L82.
17. Jaffray C, Yang J, Carter G, et al. Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Surgery, 2000, 128(2): 225-231.
18. Lv W, Lv C, Yu S, et al. Lipoxin A4 attenuation of endothelial inflammation response mimicking pancreatitis-induced lung injury. Exp Biol Med (Maywood), 2013, 238(12): 1388-1395.
19. Dasari MS, Richards KM, Alt ML, et al. Synthesis of diapocynin. J Chem Educ, 2008, 85(3): 411-412.
20. Yubero S, Ramudo L, Manso MA, et al. Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis. Biochim Biophys Acta, 2009, 1792(12): 1205-1211.
21. Kim C, Sano Y, Todorova K, et al. The kinase p38 alpha serves cell type-specific inflammatory functions in skin injury and coordinates pro- and anti-inflammatory gene expression. Nat Immunol, 2008, 9(9): 1019-1027.
22. Deng W, Abliz A, Xu S, et al. Severity of pancreatitis-associated intestinal mucosal barrier injury is reduced following treatment with the NADPH oxidase inhibitor apocynin. Mol Med Rep, 2016, 14(4): 3525-3534.
23. Hayyan M, Hashim MA, AlNashef IM. Superoxide ion: generation and chemical implications. Chem Rev, 2016, 116(5): 3029-3085.
24. Kim JM, Kim HK, Im YN, et al. FcγR/ROS/CK2α is the key inducer of NF-κB activation in a murine model of asthma. Int Arch Allergy Immunol, 2018, 175(1-2): 16-25.
25. Vaure C, Liu Y. A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol, 2014, 5: 316.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Protective effect of apocynin on lung injury induced by acute necrotic pancreatitis in rat

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content