题名

Protective Effects of N-acetylcysteine and a Prostaglandin E1 Analog, Alprostadil, Against Hepatic Ischemia: Reperfusion Injury in Rats

DOI

10.4103/2225-4110.124351

作者

Cheng-Chu Hsieh；Shu-Chen Hsieh；Jen-Hwey Chiu；Ying-Ling Wu

关键词

Alprostadil ； Ischemia-reperfusion ； N-acetylcysteine ； Prostaglandin E1 analog

期刊名称

Journal of Traditional and Complementary Medicine

卷期/出版年月

4卷1期（2014 / 01 / 01）

页次

64 - 71

内容语文

英文
中文摘要

Ischemia-reperfusion (I/R) injury has a complex pathophysiology resulting from a number of contributing factors. Therefore, it is difficult to achieve effective treatment or protection by individually targeting the mediators or mechanisms. Our aim was to analyze the individual and combined effects of N-acetylcysteine (NAC) and the prostaglandin E1 (PGE1) analog alprostadil on hepatic I/R injury in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups (six rats per group) as follows: Control group, I/R group, I/R + NAC group, I/R + alprostadil group, and I/R + NAC + alprostadil group. The rats received injections of NAC (150 mg/kg) and/or alprostadil (0.05 μg/kg) over a period of 30 min prior to ischemia. These rats were then subjected to 60 min of hepatic ischemia followed by a 60-min reperfusion period. Hepatic superoxide dismutase (SOD), catalase, and glutathione levels were significantly decreased as a result of I/R injury, but they were increased in groups treated with NAC. Hepatic malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) activities were significantly increased after I/R injury, but they were decreased in the groups with NAC treatment. Alprostadil decreased NO production, but had no effect on MDA and MPO. Histological results showed that both NAC and alprostadil were effective in improving liver tissue morphology during I/R injury. Although NAC and alprostadil did not have a synergistic effect, our findings suggest that treatment with either NAC or alprostadil has benefits for ameliorating hepatic I/R injury.
主题分类 醫藥衛生 > 中醫藥學
参考文献
  1. Acciavatti, A,Laghi Pasini, F,Capecchi, PL,Messa, GL,Lazzerini, PE,De Giorgi, L(2001).Effects of alprostadil on blood rheology and nucleoside metabolism in patients affected with lower limb chronic ischaemia.Clin Hemorheol Microcirc,24,49-57.
  2. Akhgari, M,Abdollahi, M,Kebryaeezadeh, A,Hosseini, R,Sabzevari, O(2003).Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for subchronic toxicity of malathion in blood and liver of rats.Hum Exp Toxicol,22,205-211.
  3. Araki, H,Lefer, AM(1980).Cytoprotective actions of prostacyclin during hypoxia in the isolated perfused cat liver.Am J Physiol,238,H176-H181.
  4. Arthur, MJ(1988).Reactive oxygen intermediates and liver injury.J Hepatol,6,125-131.
  5. Aruoma, OI,Halliwell, B,Hoey, BM,Butler, J(1989).The antioxidant action of n‑acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid.Free Radic Biol Med,6,593-597.
  6. Bonventre, JV,Weinberg, JM(2003).Recent advances in the pathophysiology of ischemic acute renal failure.J Am Soc Nephrol,14,2199-2210.
  7. Buege, JA,Aust, SD(1978).Microsomal lipid peroxidation.Methods Enzymol,52,302-310.
  8. Canada, AT,Stein, K,Martel, D,Watkins, WD(1992).Biochemical appraisal of models for hepatic ischemia-reperfusion injury.Circ Shock,36,163-168.
  9. Chiu, JH,Ho, CT,Wei, YH,Lui, WY,Hong, CY(1997).In vitro and in vivo protective effect of honokiol on rat liver from peroxidative injury.Life Sci,61,1961-1971.
  10. Chiu, JH,Tsou, MT,Tung, HH,Tai, CH,Tsai, SK,Chih, CL(2003).Preconditioned somatothermal stimulation on median nerve territory increases myocardial heat shock protein 70 and protects rat hearts against ischemia‑reperfusion injury.J Thorac Cardiovasc Surg,125,678-685.
  11. Cuzzocrea, S,Mazzon, E,Costantino, G,Serraino, I,De Sarro, A,Caputi, AP(2000).Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury.Cardiovasc Res,47,537-548.
  12. Cuzzocrea, S,Reiter, RJ(2001).Pharmacological action of melatonin in shock, inflammation and ischemia/reperfusion injury.Eur J Pharmacol,426,1-10.
  13. de la Monte, SM,Arcidi, JM,Moore, GW,Hutchins, GM(1984).Midzonal necrosis as a pattern of hepatocellular injury after shock.Gastroenterology,86,627-631.
  14. De Vries, N,De Flora, S(1993).N-acetyl-l-cysteine.J Cell Biochem Suppl,17F,270-277.
  15. Decker, K(1990).Biologically active products of stimulated liver macrophages (kupffer cells).Eur J Biochem,192,245-261.
  16. Greig, PD,Woolf, GM,Abecassis, M,Forster, J,Strasberg, SM,Taylor, BR(1989).Prostaglandin e1 for primary nonfunction following liver transplantation.Transplant Proc,21,3360-3361.
  17. Heinzelmann, M,Mercer‑Jones, MA,Passmore, JC(1999).Neutrophils and renal failure.Am J Kidney Dis,34,384-399.
  18. Hillegass, LM,Griswold, DE,Brickson, B,Albrightson-Winslow, C(1990).Assessment of myeloperoxidase activity in whole rat kidney.J Pharmacol Methods,24,285-295.
  19. Holdiness, MR(1991).Clinical pharmacokinetics of n‑acetylcysteine.Clin Pharmacokinet,20,123-134.
  20. Ischiropoulos, H,Beckman, JS(2003).Oxidative stress and nitration in neurodegeneration: Cause, effect, or association?.J Clin Invest,111,163-169.
  21. Jaeschke, H,Farhood, A,Bautista, AP,Spolarics, Z,Spitzer, JJ(1993).Complement activates kupffer cells and neutrophils during reperfusion after hepatic ischemia.Am J Physiol,264,G801-G809.
  22. Jaeschke, H,Farhood, A,Bautista, AP,Spolarics, Z,Spitzer, JJ,Smith, CW(1993).Functional inactivation of neutrophils with a mac‑1 (cd11b/cd18) monoclonal antibody protects against ischemia-reperfusion injury in rat liver.Hepatology,17,915-923.
  23. Jaeschke, H,Farhood, A,Smith, CW(1990).Neutrophils contribute to ischemia/reperfusion injury in rat liver In Vivo.FASEB J,4,3355-3359.
  24. Knight, KR,MacPhadyen, K,Lepore, DA,Kuwata, N,Eadie, PA,O‘Brien, BM(1991).Enhancement of ischaemic rabbit skin flap survival with the antioxidant and free-radical scavenger n-acetylcysteine.Clin Sci,81,31-36.
  25. Koo, A,Komatsu, H,Tao, G,Inoue, M,Guth, PH,Kaplowitz, N(1992).Contribution of no‑reflow phenomenon to hepatic injury after ischemia‑reperfusion: Evidence for a role for superoxide anion.Hepatology,15,507-514.
  26. Kornberg, A,Schotte, U,Kupper, B,Hommann, M,Scheele, J(2004).Impact of selective prostaglandin e1 treatment on graft perfusion and function after liver transplantation.Hepatogastroenterology,51,526-531.
  27. Koshitani, T,Kodama, T,Sato, H,Takaaki, J,Imamura, Y,Kato, K(2002).A synthetic prostaglandin e1 analog, alprostadil alfadex, relaxes sphincter of oddi in humans.Dig Dis Sci,47,152-156.
  28. Kumar, O,Sugendran, K,Vijayaraghavan, R(2003).Oxidative stress associated hepatic and renal toxicity induced by ricin in mice.Toxicon,41,333-338.
  29. Lin, YH,Chiu, JH,Tung, HH,Tsou, MT,Lui, WY,Wu, CW(2001).Preconditioning somatothermal stimulation on right seventh intercostal nerve territory increases hepatic heat shock protein 70 and protects the liver from ischemia‑reperfusion injury in rats.J Surg Res,99,328-334.
  30. Liu, Z,Xu, Z,Shen, W,Li, Y,Zhang, J,Ye, X(2004).Effect of pharmacologic preconditioning with tetrandrine on subsequent ischemia/reperfusion injury in rat liver.World J Surg,28,620-624.
  31. Look, MP,Rockstroh, JK,Rao, GS,Barton, S,Lemoch, H,Kaiser, R(1998).Sodium selenite and n-acetylcysteine in antiretroviral-naive hiv‑1‑infected patients: A randomized, controlled pilot study.Eur J Clin Invest,28,389-397.
  32. Manson, PN,Anthenelli, RM,Im, MJ,Bulkley, GB,Hoopes, JE(1983).The role of oxygen‑free radicals in ischemic tissue injury in island skin flaps.Ann Surg,198,87-90.
  33. Manson, PN,Narayan, KK,Im, MJ,Bulkley, GB,Hoopes, JE(1986).Improved survival in free skin flap transfers in rats.Surgery,99,211-215.
  34. Mavier, P,Preaux, AM,Guigui, B,Lescs, MC,Zafrani, ES,Dhumeaux, D(1988).In vitro toxicity of polymorphonuclear neutrophils to rat hepatocytes: Evidence for a proteinase‑mediated mechanism.Hepatology,8,254-258.
  35. McCord, JM(1985).Oxygen‑derived free radicals in postischemic tissue injury.N Engl J Med,312,159-163.
  36. Moldeus, P,CotgreaveI, A,Berggren, M(1986).Lung protection by a thiol-containing antioxidant: N‑acetylcysteine.Respiration,50(Suppl 1),31-42.
  37. Nagasaki, H,Nakano, H,Boudjema, K,Jaeck, D,Alexandre, E,Baek, Y(1998).Efficacy of preconditioning with n‑acetylcysteine against reperfusion injury after prolonged cold ischaemia in rats liver in which glutathione had been reduced by buthionine sulphoximine.Eur J Surg,164,139-146.
  38. Oreopoulos, GD,Wu, H,Szaszi, K,Fan, J,Marshall, JC,Khadaroo, RG(2004).Hypertonic preconditioning prevents hepatocellular injury following ischemia/reperfusion in mice: A role for interleukin 10.Hepatology,40,211-220.
  39. Pan, PJ,Chan, RC,Yang, AH,Chou, CL,Cheng, YF,Chiu, JH(2008).Protective effects of preconditioned local somatothermal stimulation on neuromuscular plasticity against ischemia--reperfusion injury in rats.J Orthop Res,26,1670-1674.
  40. Reiter, RJ,Acuna-Castroviejo, D,Tan, DX,Burkhardt, S(2001).Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system.Ann N Y Acad Sci,939,200-215.
  41. Russell, WJ,Jackson, RM(1993).Mnsod protein content changes in hypoxic/hypoperfused lung tissue.Am J Respir Cell Mol Biol,9,610-616.
  42. Sindram, D,Porte, RJ,Hoffman, MR,Bentley, RC,Clavien, PA(2001).Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: A kupffer cell‑mediated injury.FASEB J,15,1230-1232.
  43. Staal, FJ,Ela, SW,Roederer, M,Anderson, MT,Herzenberg, LA(1992).Glutathione deficiency and human immunodeficiency virus infection.Lancet,339,909-912.
  44. Stewart, JR,Blackwell, WH,Crute, SL,Loughlin, V,Greenfield, LJ,Hess, ML.(1983).Inhibition of surgically induced ischemia/reperfusion injury by oxygen free radical scavengers.J Thorac Cardiovasc Surg,86,262-272.
  45. Suzuki, S,Nakamura, S,Koizumi, T,Sakaguchi, S,Baba, S,Muro, H(1991).The beneficial effect of a prostaglandin i2 analog on ischemic rat liver.Transplantation,52,979-983.
  46. Tafazoli, S,Spehar, DD,O‘Brien, PJ(2005).Oxidative stress mediated idiosyncratic drug toxicity.Drug Metab Rev,37,311-325.
  47. Takahashi, Y,Tamaki, T,Tanaka, M,Konoeda, Y,Kawamura, A,Katori, M(1998).Efficacy of heat‑shock proteins induced by severe fasting to protect rat livers preserved for 72 hours from cold ischemia/reperfusion injury.Transplant Proc,30,3700-3702.
  48. Totsuka, E,Todo, S,Zhu, Y,Ishizaki, N,Kawashima, Y,Jin, MB(1998).Attenuation of ischemic liver injury by prostaglandin e1 analogue, misoprostol, and prostaglandin i2 analogue, op‑41483.J Am Coll Surg,187,276-286.
  49. Vajdova, K,Heinrich, S,Tian, Y,Graf, R,Clavien, PA(2004).Ischemic preconditioning and intermittent clamping improve murine hepatic microcirculation and kupffer cell function after ischemic injury.Liver Transpl,10,520-528.
  50. Vollmar, B,Glasz, J,Leiderer, R,Post, S,Menger, MD(1994).Hepatic microcirculatory perfusion failure is a determinant of liver dysfunction in warm ischemia‑reperfusion.Am J Pathol,145,1421-1431.
  51. Weiss, SJ,Ward, PA(1982).Immune complex induced generation of oxygen metabolites by human neutrophils.J Immunol,129,309-313.
  52. Yang, H,Majno, P,Morel, P,Toso, C,Triponez, F,Oberholzer, J(2002).Prostaglandin e (1) protects human liver sinusoidal endothelial cell from apoptosis induced by hypoxia reoxygenation.Microvasc Res,64,94-103.
  53. Yoshikawa, T,Murakami, M,Yoshida, N,Seto, O,Kondo, M(1983).Effects of superoxide dismutase and catalase on disseminated intravascular coagulation in rats.Thromb Haemost,50,869-872.
  54. Zimmerman, BJ,Grisham, MB,Granger, DN(1990).Role of oxidants in ischemia/reperfusion‑induced granulocyte infiltration.Am J Physiol,258,G185-G190.
print cancel