Activation of Adenosine 2A Receptor Attenuating Oxidative Stress on Small-for-Size Liver Transplantation_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHU Jianfei ¹ , TANG Liming ² , LI Dechun ¹

1.Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China;;
2.Department of General Surgery, Changzhou No.2 Hospital Affiliated to Nanjing Medical University, Changzhou 213003, Jiangsu Province, China;

Corresponding author：

Keywords：

Adenosine receptor; Oxidative stress; Ischemia-reperfusion injury; Small-for-size liver transplantation

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Objective To investigate the effects of adenosine 2A receptor (A2AR) activation on oxidative stress in small-forsize liver transplantation.
Methods A rat orthotopic liver transplantation model was performed using 40% graft, 18 recipients were given intravenously saline (control group), CGS21680 (A2AR agonist, CGS21680 group) or ZM241385 (A2AR antagonist, CGS21680+ZM241385 group) randomly. Aspartate aminotransferase (AST), enzymatic antioxidants 〔superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GSH-Px)〕, non-enzymatic antioxidants 〔ascorbic acid (AA); glutathione (GSH); α-tocopherol (TOC)〕 and lipid oxidant metabolites malondialdehyde (MDA) were measured and analyzed at 6 h after reperfusion.
Results Compared with the control group and CGS21680+ZM241385 group, A2AR activation increased the activities of SOD and GSHPx (P lt;0.05), reduced the productions of AST and MDA (P lt;0.05), increased the levels of AA, GSH and TOC (P lt;0.05) in CGS21680 group. But there was no significant change in CAT activity (P gt;0.05) among 3 groups.
Conclusions A2AR activation improves the antioxidant enzyme activities, promotes the production of antioxidants, and slowes down the increase in MDA level, depresses of the increase in AST activity. A2AR activation suppresses oxidative damage and increases the antioxidant capacity which in turn minimizes their harmful effects of ischemia-reperfusion in small-for-size liver transplantation.

Citation： ZHU Jianfei ,TANG Liming,LI Dechun. Activation of Adenosine 2A Receptor Attenuating Oxidative Stress on Small-for-Size Liver Transplantation. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(3): 243-247. doi: Copy

1.	Ikegami T, Shimada M, Imura S, et al. Current concept of smallforsize grafts in living donor liver transplantation [J]. Surg Today, 2008; 38(11): 971982.
2.	Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin1 transfer improves survival and early graft function after ischemia and reperfusion in rat smallforsize liver transplantation model [J]. Transpl Int， 2008; 21(4): 372383.
3.	Yao A, Li X, Pu L, et al. Impaired hepatic regeneration by ischemic preconditioning in a rat model of smallforsize liver transplantation [J]. Transpl Immunol, 2007; 18(1): 3743.
4.	Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcoholinduced liver injury [J]. Arch Toxicol, 2009; 83(6):519548.
5.	Sucher R, Gehwolf P, Kaier T, et al. Intracellular signaling pathways control mitochondrial events associated with the development of ischemia/reperfusionassociated damage [J]. Transpl Int, 2009; 22(9): 922930.
6.	Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in smallforsize liver transplantation [J]. Transpl Int, 2007; 20(1): 93101.
7.	Uchiyama S, Shimizu T, Shirasawa T. CuZnSOD deficiency causes ApoB degradation and induces hepatic lipid accumulation by impaired lipoprotein secretion in mice [J]. J Biol Chem, 2006; 281(42): 3171331719.
8.	Décordé K, Ventura E, Lacan D, et al. An SOD rich melon extract Extramel prevents aortic lipids and liver steatosis in dietinduced model of atherosclerosis [J]. Nutr Metab Cardiovasc Dis, 2009 Aug 18. DOI:10.1016/j.numecd.2009.04.017.
9.	卢峻, 陈英松, 阿古拉, 等. 蒙医温针对大鼠疲劳模型肝脏MDA、GSH 含量及GSHPX、SOD活性的影响 [J]. 针刺研究, 2007; 32(3): 167169.
10.	Kim SJ, Lee JW, Jung YS, et al. Ethanolinduced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice [J]. J Hepatol, 2009; 50(6): 11841191.
11.	Jiang WW, Kong LB, Li GQ, et al. Expression of iNOS in early injury in a rat model of smallforsize liver transplantation [J]. Hepatobiliary Pancreat Dis Int, 2009; 8(2): 146151.
12.	孙要武, 董艳梅, 吴嘉慧, 等. 复合维生素B 和谷胱甘肽对脂肪肝的保护作用 [J]. 卫生研究, 2009; 38(4): 413416.
13.	Kang P, Dalvie D, Smith E, et al. Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts [J]. Chem Res Toxicol, 2009; 22(1): 106117.
14.	Crincoli CM, Patel NN, Harvison PJ. Formation of glutathione (GSH) conjugates from 3(3, 5dichlorophenyl) 2, 4thiazolidinedione (DCPT) by rat liver microsomes [J]. FASEB J, 2007; 21: 731.2.
15.	Chou PT, Khan AU. Lascorbic acid quenching of singlet delta molecular oxygen in aqueous media: generalized antioxidant property of vitamin C [J]. Biochem Biophys Res Commun, 1983; 115(3): 932937.
16.	Dillard CJ, Gavino VC, Tappel AL. Relative antioxidant effectiveness of αtocopherol and ωtocopherol in ironloaded rats [J]. J Nutr, 1983; 113(11): 22662273.
17.	Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more [J]. Free Radic Biol Med, 2007; 43(1): 415.
18.	Soden JS, Devereaux MW, Haas JE, et al. Subcutaneous vitamin E ameliorates liver injury in an in vivo model of steatocholestasis [J]. Hepatology, 2007; 46(2): 485495.
19.	Shang F, Lu M, Dudek E, et al. Vitamin C and vitamin E restore the resistance of GSHdepleted lens cells to H2O2 [J]. Free Radic Biol Med, 2003; 34(5): 521530.
20.	Ross D. Glutathione, free radicals and chemotherapeutic agents. Mechanisms of freeradical induced toxicity and glutathionedependent protection [J]. Pharmacol Ther, 1988; 37(2): 231249.
21.	Reiter RJ, Tan DX, Manchester LC, et al. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence [J]. Cell Biochem Biophys, 2001; 34(2): 237256.
22.	Frank J, Lundh T, Parker RS, et al. Dietary (+) catechin and BHT markedly increase αtocopherol concentrations in rats by a tocopherolωhydroxylaseindependent mechanism [J]. J Nutr, 2003; 133(10): 31953199.
23.	Ramanathan K, Shila S, Kumaran S, et al. Protective role of ascorbic acid and alphatocopherol on arsenicinduced microsomal dysfunctions [J]. Hum Exp Toxicol, 2003; 22(3): 129136.
24.	Evans ZP, Ellett JD, Fariss MW, et al. Vitamin E succinate reduces ischemia/reperfusion injury in steatotic livers [J]. Transplant Proc, 2008; 40(10): 33273329.
25.	Hiroyuki A. Molecular mechanisms of αtocopherol transfer protein (αTTP) dependent αtocopherol transfer in hepatocytes [J]. Jpn J Physiol, 2005; 55(Suppl): S31.

1. Ikegami T, Shimada M, Imura S, et al. Current concept of smallforsize grafts in living donor liver transplantation [J]. Surg Today, 2008; 38(11): 971982.
2. Song J, Zhang YW, Yao AH, et al. Adenoviral cardiotrophin1 transfer improves survival and early graft function after ischemia and reperfusion in rat smallforsize liver transplantation model [J]. Transpl Int， 2008; 21(4): 372383.
3. Yao A, Li X, Pu L, et al. Impaired hepatic regeneration by ischemic preconditioning in a rat model of smallforsize liver transplantation [J]. Transpl Immunol, 2007; 18(1): 3743.
4. Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcoholinduced liver injury [J]. Arch Toxicol, 2009; 83(6):519548.
5. Sucher R, Gehwolf P, Kaier T, et al. Intracellular signaling pathways control mitochondrial events associated with the development of ischemia/reperfusionassociated damage [J]. Transpl Int, 2009; 22(9): 922930.
6. Tang LM, Wang YP, Wang K, et al. Protective effect of adenosine A2A receptor activation in smallforsize liver transplantation [J]. Transpl Int, 2007; 20(1): 93101.
7. Uchiyama S, Shimizu T, Shirasawa T. CuZnSOD deficiency causes ApoB degradation and induces hepatic lipid accumulation by impaired lipoprotein secretion in mice [J]. J Biol Chem, 2006; 281(42): 3171331719.
8. Décordé K, Ventura E, Lacan D, et al. An SOD rich melon extract Extramel prevents aortic lipids and liver steatosis in dietinduced model of atherosclerosis [J]. Nutr Metab Cardiovasc Dis, 2009 Aug 18. DOI:10.1016/j.numecd.2009.04.017.
9. 卢峻, 陈英松, 阿古拉, 等. 蒙医温针对大鼠疲劳模型肝脏MDA、GSH 含量及GSHPX、SOD活性的影响 [J]. 针刺研究, 2007; 32(3): 167169.
10. Kim SJ, Lee JW, Jung YS, et al. Ethanolinduced liver injury and changes in sulfur amino acid metabolomics in glutathione peroxidase and catalase double knockout mice [J]. J Hepatol, 2009; 50(6): 11841191.
11. Jiang WW, Kong LB, Li GQ, et al. Expression of iNOS in early injury in a rat model of smallforsize liver transplantation [J]. Hepatobiliary Pancreat Dis Int, 2009; 8(2): 146151.
12. 孙要武, 董艳梅, 吴嘉慧, 等. 复合维生素B 和谷胱甘肽对脂肪肝的保护作用 [J]. 卫生研究, 2009; 38(4): 413416.
13. Kang P, Dalvie D, Smith E, et al. Bioactivation of lumiracoxib by peroxidases and human liver microsomes: identification of multiple quinone imine intermediates and GSH adducts [J]. Chem Res Toxicol, 2009; 22(1): 106117.
14. Crincoli CM, Patel NN, Harvison PJ. Formation of glutathione (GSH) conjugates from 3(3, 5dichlorophenyl) 2, 4thiazolidinedione (DCPT) by rat liver microsomes [J]. FASEB J, 2007; 21: 731.2.
15. Chou PT, Khan AU. Lascorbic acid quenching of singlet delta molecular oxygen in aqueous media: generalized antioxidant property of vitamin C [J]. Biochem Biophys Res Commun, 1983; 115(3): 932937.
16. Dillard CJ, Gavino VC, Tappel AL. Relative antioxidant effectiveness of αtocopherol and ωtocopherol in ironloaded rats [J]. J Nutr, 1983; 113(11): 22662273.
17. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more [J]. Free Radic Biol Med, 2007; 43(1): 415.
18. Soden JS, Devereaux MW, Haas JE, et al. Subcutaneous vitamin E ameliorates liver injury in an in vivo model of steatocholestasis [J]. Hepatology, 2007; 46(2): 485495.
19. Shang F, Lu M, Dudek E, et al. Vitamin C and vitamin E restore the resistance of GSHdepleted lens cells to H2O2 [J]. Free Radic Biol Med, 2003; 34(5): 521530.
20. Ross D. Glutathione, free radicals and chemotherapeutic agents. Mechanisms of freeradical induced toxicity and glutathionedependent protection [J]. Pharmacol Ther, 1988; 37(2): 231249.
21. Reiter RJ, Tan DX, Manchester LC, et al. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence [J]. Cell Biochem Biophys, 2001; 34(2): 237256.
22. Frank J, Lundh T, Parker RS, et al. Dietary (+) catechin and BHT markedly increase αtocopherol concentrations in rats by a tocopherolωhydroxylaseindependent mechanism [J]. J Nutr, 2003; 133(10): 31953199.
23. Ramanathan K, Shila S, Kumaran S, et al. Protective role of ascorbic acid and alphatocopherol on arsenicinduced microsomal dysfunctions [J]. Hum Exp Toxicol, 2003; 22(3): 129136.
24. Evans ZP, Ellett JD, Fariss MW, et al. Vitamin E succinate reduces ischemia/reperfusion injury in steatotic livers [J]. Transplant Proc, 2008; 40(10): 33273329.
25. Hiroyuki A. Molecular mechanisms of αtocopherol transfer protein (αTTP) dependent αtocopherol transfer in hepatocytes [J]. Jpn J Physiol, 2005; 55(Suppl): S31.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Activation of Adenosine 2A Receptor Attenuating Oxidative Stress on Small-for-Size Liver Transplantation

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