题名

Inhibition of Inducible Nitric Oxide Synthase in Murine Visceral Larva Migrans: Effects on Lung and Liver Damage

作者

Cihan Demirci;Aysen Gargili;Aslι Kandil;Handan Cetinkaya;Ilhan Uyaner;Basak Boynuegri;M. Koray Gumustas

关键词

Toxocara canis ; iNOS ; visceral larva migrans ; oxidative stress

期刊名称

The Chinese Journal of Physiology

卷期/出版年月

49卷6期(2006 / 12 / 01)

页次

326 - 334

内容语文

英文

英文摘要

The roles of nitric oxide production and oxidative process were studied in mice infected with Toxocara canis and treated with aminoguanidine which is a specific inhibitor of inducible nitric oxide synthase (iNOS). Relations of nitric oxide synthase inhibition and tissue pathology were assessed by biochemical, histological and immunohistochemical methods. In experiments, Balb/c albino mice were inoculated with T. canis eggs either with or without aminoguanidine treatment or alone, at 24(superscript th), 48(superscript th) hours and on 7(superscript th) days. LPx and SOD values in liver tissue and plasma were measured. Liver and lung tissues were evaluated for the pathological lesions. The expression of eNOS and iNOS in both tissues were studied with immunohistochemistry in the same intervals. We observed significant differences between T. canis infected and aminoguanidine treated animals. Larval toxocarosis led to oxidative stress elevation in plasma. Microscopic examination of the liver histological sections revealed pathological lesions in the hepatic parenchyma in infected mice. In the mice received T. canis eggs plus aminoguanidine, the sinusoidal areas were enlarged. Histological lesions were more severe at 48 hours after infection. Numbers of eNOS and iNOS expressing epithelial cells were increased in the T. canis infected mice. The activities of eNOS and iNOS were also observed in the body of the larvae which have migrated to lung and liver. As a result, we have demonstrated that in vivo production of eNO and iNO during T. canis infection cause direct host damages and it is strongly related to the oxidative stress. We propose that larval NO can also be effective in larval migration, but it needs further investigation on distribution of NO in larvae.

主题分类 醫藥衛生 > 基礎醫學
参考文献
  1. Gargιlι, A.,Demirci, C.,Kandil, A.,Cetinkaya, H.,Atukeren, P.,GümüStaS, M.K.(2004).In vivo inhibition of inducible nitric oxide and evaluation of the brain tissue damage induced by Toxocara canis larvae in experimentally infected mice.Chinese J. Physiol.,26,273-281.
    連結:
  2. Ascenzi, P.,Gradoni, L.(2002).Nitric oxide limits parasite development in vectors and in invertebrate intermediate hosts.IUBMB Life,53,121-123.
  3. Bergmeyer, H.U.,Scheibe, P.,Wahlefeld, A.W.(1978).Optimization of methods for aspartate aminotransferase and alanine aminotransferase.Clin. Chem.,24,58-73.
  4. Bowman, J.W.,Winterrowd, C.A.,Friedman, A.R.,Thompson, D.P.,Klein, R.D.,Davis, J.P.,Maule, A.G.,Blair, K.L.,Geary, T.G.(1995).Nitric oxide mediates the inhibitory effects of SDPNFLRFamide, a nematode FMRFamide-related neuropeptide, in Ascaris suum.J. Neurophysiol,74,1880-1888.
  5. Brunet, L.R.,Beall, M.,Dunne, D.W.,Pearce, E.J.(1999).Nitric oxide and the Th2 response combine to prevent severe hepatic damage during Schistosoma mansoni infection.J. Immunol,163,4976-4984.
  6. Brunet, L.R.,Finkelman, F.D.,Cheever, A.W.,Kopf, M.A.,Pearce, E.J.(1997).IL-4 protects against TNF-alpha-mediated cachexia and death during acute schistosomiasis.J. Immunol,159,777-785.
  7. Buege, J.A.,Aust, S.D.(1978).Microsomal lipid peroxydation.Methods Enzymol,12,302-310.
  8. El-Sokkary, G.H.,Omar, H.M.,Hassanein, A.M.M.,Cuzzocrea, S.,Reiter, R.J.(2002).Melatonin reduces oxidative damage and increases survival of mice infected with Schistosoma mansoni.Free Radic. Biol. Med.,32,319-332.
  9. Espinosa, E.,Perez Arellano, J.L.,Ciarranza, C.,Collia, F.,Muro, A.(2002).In vivo inhibition of inducible nitric oxide synthase decreases lung injury induced by Toxocara canis in experimentally infected rats.Parasite Immunol,24,511-520.
  10. Espinoza, E.,Muro, A.,Sanchez-Martin, M.M.,Casanueva, P.,Perez-Arellano, J.L.(2002).Toxocara canis antigens stimulate the production of nitric oxide and prostaglandin E2 by rat alveolar macrophages.Parasite Immunol,24,311-319.
  11. Espinoza, E.,Perez-Arellano, J.L.,Vicente, B.,Muro, A.(2002).Cytoplasmic signaling pathways in alveolar macrophages involved in the production of nitric oxide after stimulation with excretory/ secretory antigens of Toxocara canis.Parasite Immunol,24,535-544.
  12. Fan, C.K.,Lin, Y.H.,Hung, C.C.,Chang, S.F.,Su, K.E.(2004).Enhanced inducible nitric oxide synthase expression and nitrotyrosine accumulation in experimental granulomatous hepatitis caused by Toxocara canis in mice.Parasite Immunol,26,273-281.
  13. Galvin, T.(1964).Experimental Toxocara canis infections in chickens and pigeons.J. Parasitol,50,124-127.
  14. Garside, P.,Kennedy, M.W.,Wakelin, D.,Lawrence, C.E.(2000).Immunopathology of intestinal helminth infection.Parasite Immunol,22,605-612.
  15. Garthwaite, J.(1991).Glutamate, nitric oxide and cell-cell signaling in the nervous system.Trends Neurosci.,14,60-67.
  16. James, S.L.(1995).Role of nitric oxide in parasitic infections.Microbiol. Rev.,59,533-547.
  17. Khan, I.A.,Schwartzman, J.D.,Matsuura, T.,Kasper, L.H.(1997).A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice.Proc. Natl. Acad. Sci. USA,94,13955-13960.
  18. Lawrence, C.E.,Paterson, J.C.,Wei, X.Q.,Liew, F.Y.,Garside, P.,Kennedy, M.W.(2000).Nitric oxide mediates intestinal pathology but not immune expulsion during Trichinella spiralis infection in mice.J. Immunol,164,4229-4234.
  19. Nilsson, B.O.(1999).Biological effects of aminoguanidine: an update.Inflamm. Res.,48,509-515.
  20. Oliveira, F.J.,Cecchini, R.(2000).Oxidative stress of liver in hamsters infected with Leishmania (L.) chagasi.J. Parasitol,86,1067-1072.
  21. Oshima, T.(1961).Standardization of techniques for infecting mice with Toxocara canis and observations on the normal migration routes of the larvae.J. Parasitol,47,652-656.
  22. Oswald, I.P.,James, S.L.(1996).Nitrogen oxide in host defense against parasites.Methods,10,8-14.
  23. Oswald, I.P.,Wynn, T.A.,Sher, A.,James, S.L.(1994).NO as an effector molecule of parasite killing: modulation of its synthesis by cytokines.Comp. Biochem. Physiol. Pharmacol. Toxicol. Endocrinol,108,11-18.
  24. Palmer, R.M.J.,Ferrige, A.G.,Moncada, S.(1987).Nitric oxide release accounts for the biological activity of endothelium derived-relaxing factor.Nature,327,524-526.
  25. Rajan, T.V.,Porte, P.,Yates, J.A.,Keefer, L.,Schultz, L.D.(1996).Role of nitric oxide in host defence against an extracellular, metazoan parasite, Brugia malayi.Infect. Immun,64,3351-3353.
  26. Schluter, D.,Deckert, M.,Hof, H.,Frei, K.(2001).Toxoplasma gondii infection of neurons induces neuronal cytokine and chemokine production, but gamma interferon- and tumor necrosis factorstimulated neurons fail to inhibit the invasion and growth of T.gondii. Infect. Immun,69,7889-7893.
  27. Selkirk, M.E.,Smith, V.P.,Thomas, G.R.,Gounaris, K.(1998).Resistance of filarial nematode parasites to oxidative stress.Int. J. Parasitol,28,1315-1332.
  28. Soh, C. T.(1958).The distribution and persistence of hookworm larvae in the tissues of mice in relation to species and to route of inoculation.J. Parasitol,44,545-519.
  29. Sun, Y.,Oberley, L.W.,Li, Y.A.(1988).Simple method for clinical assay of superoxide dismutase.Clin. Chem,34,497-500.
  30. Taylor, B.S.,Alarcon, L.H.,Billiar, T.R.(1998).Inducible nitric oxide synthase in the liver: regulation and function.Biochemistry,63,766-781.
  31. Taylor, M.J.,Cross, H.F.,Mohammed, A.A.,Trees, A.J.,Bianco, A.E.(1996).Susceptibility of Brugia malayi and Onchocerca lienalis microfilariae to nitric oxide and hydrogen peroxide in cellfree culture and from IFN gamma-activated macrophages.Parasitology,112,315-322.
  32. Wandurska-Nowak, E.,Wisniewska, J.(2002).Release of nitric oxide during experimental trichinellosis in mice.Parasitol. Res.,88,708-711.
  33. Wynn, T.A.,Oswald, I.P.,Eltoum, I.A.,Caspar, P.,Lowenstein, C. J.,Lewis, F.A.,James, S.L.,Sher, A.(1994).Elevated expression of Th1 cytokines and NO synthase in the lungs of vaccinated mice after challenge infection with Schistosoma mansoni.J. Immunol,153,5200-5209.
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