Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 2000;9(2):101–107. doi: 10.1080/096293500411569

Local haemorrhage induced by Bothrops jararaca venom: relationship to neurogenic inflammation.

L R Gonçalves 1, M Mariano 1
PMCID: PMC1781750  PMID: 10958383

Abstract

We investigated morphological alterations induced by s.c. injection of 2.5 microg of Bothrops jararaca venom in rats. Intense disorganisation of collagen fibres was observed 1 min after the venom injection, particularly at regions near vessels and nerves. Mast cells were degranulated, and erythrocytes were seen leaving venules throughout the endothelial junctions. At this time, damaged endothelial cells were not observed. In rats envenomed as above, but immediately after cardiorespiratory failure induced by deep ether anaesthesia, alterations in the connective tissue structures, as previously described, were not observed. The mediation of this haemorrhage was investigated by injecting the venom into the foot pad of mice and compared to the mediation of oedema. Local haemorrhage was significantly reduced in mice pre-treated with capsaicin or guanethidine or submitted to a surgical section of sciatic and saphenous nerves. In these animals, oedema was not affected. Groups treated with methysergide or morphine showed both haemorrhage and oedema significantly reduced. Indomethacin or dexamethasone pre-treatments significantly reduced the oedema, but not the haemorrhage. Moreover, in animals treated with promethazine or mepyramine, oedema and haemorrhage were not affected. These data suggest that local haemorrhage induced by Bothrops jararaca venom is partially controlled by serotonin and neurohumoral mediators. Furthermore, results indicate that haemorrhage and oedema are mediated by different pharmacological systems.

Full Text

The Full Text of this article is available as a PDF (852.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baramova E. N., Shannon J. D., Bjarnason J. B., Fox J. W. Degradation of extracellular matrix proteins by hemorrhagic metalloproteinases. Arch Biochem Biophys. 1989 Nov 15;275(1):63–71. doi: 10.1016/0003-9861(89)90350-0. [DOI] [PubMed] [Google Scholar]
  2. Baramova E. N., Shannon J. D., Bjarnason J. B., Fox J. W. Identification of the cleavage sites by a hemorrhagic metalloproteinase in type IV collagen. Matrix. 1990 May;10(2):91–97. doi: 10.1016/s0934-8832(11)80175-7. [DOI] [PubMed] [Google Scholar]
  3. Barros S. F., Friedlanskaia I., Petricevich V. L., Kipnis T. L. Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom. Mediators Inflamm. 1998;7(5):339–346. doi: 10.1080/09629359890866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barthó L., Szolcsányi J. Opiate agonists inhibit neurogenic plasma extravasation in the rat. Eur J Pharmacol. 1981 Jul 17;73(1):101–104. doi: 10.1016/0014-2999(81)90152-7. [DOI] [PubMed] [Google Scholar]
  5. Bjarnason J. B., Fox J. W. Hemorrhagic metalloproteinases from snake venoms. Pharmacol Ther. 1994;62(3):325–372. doi: 10.1016/0163-7258(94)90049-3. [DOI] [PubMed] [Google Scholar]
  6. Bjarnason J. B., Hamilton D., Fox J. W. Studies on the mechanism of hemorrhage production by five proteolytic hemorrhagic toxins from Crotalus atrox venom. Biol Chem Hoppe Seyler. 1988 May;369 (Suppl):121–129. [PubMed] [Google Scholar]
  7. Brown J. H., Kissel J. W., Lish P. M. Studies on the acute inflammatory response. I. Involvement of the central nervous system in certain models of inflammation. J Pharmacol Exp Ther. 1968 Mar;160(1):231–242. [PubMed] [Google Scholar]
  8. Böhm G. M. Vascular events in inflammation. Agents Actions Suppl. 1977;(3):31–50. doi: 10.1007/978-3-0348-7290-4_4. [DOI] [PubMed] [Google Scholar]
  9. Búrigo A. C., Calixto J. B., Medeiros Y. S. Pharmacological profile of rat pleurisy induced by Bothrops jararaca venom. J Pharm Pharmacol. 1996 Jan;48(1):106–111. doi: 10.1111/j.2042-7158.1996.tb05887.x. [DOI] [PubMed] [Google Scholar]
  10. CHAPMAN L. F., GOODELL H. THE PARTICIPATION OF THE NERVOUS SYSTEM IN THE INFLAMMATORY REACTION. Ann N Y Acad Sci. 1964 Aug 27;116:990–1017. doi: 10.1111/j.1749-6632.1964.tb52564.x. [DOI] [PubMed] [Google Scholar]
  11. Cardoso J. L., Fan H. W., França F. O., Jorge M. T., Leite R. P., Nishioka S. A., Avila A., Sano-Martins I. S., Tomy S. C., Santoro M. L. Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil. Q J Med. 1993 May;86(5):315–325. [PubMed] [Google Scholar]
  12. Casellas A. M., Guardiola H., Renaud F. L. Inhibition by opioids of phagocytosis in peritoneal macrophages. Neuropeptides. 1991 Jan;18(1):35–40. doi: 10.1016/0143-4179(91)90161-b. [DOI] [PubMed] [Google Scholar]
  13. Chaves F., Barboza M., Gutiérrez J. M. Pharmacological study of edema induced by venom of the snake Bothrops asper (terciopelo) in mice. Toxicon. 1995 Jan;33(1):31–39. doi: 10.1016/0041-0101(94)00135-u. [DOI] [PubMed] [Google Scholar]
  14. Cury Y., Teixeira C. F., Sudo L. S. Edematogenic responses induced by Bothrops jararaca venom in rats: role of lymphocytes. Toxicon. 1994 Nov;32(11):1425–1431. doi: 10.1016/0041-0101(94)90414-6. [DOI] [PubMed] [Google Scholar]
  15. Detrait J., Jacob J. Antagonists of mouse paw oedema induced by Habu snake (Trimeresurus flavoviridis) venom. Inhibitions by various antagonists administered alone or in combinations. Jpn J Exp Med. 1988 Dec;58(6):249–259. [PubMed] [Google Scholar]
  16. Detrait J., Jacob J. Mouse paw oedema induced by Habu snake (Trimeresurus flavoviridis) venom: inhibition by morphine, naloxone and methylnaloxone alone or in combinations. Jpn J Exp Med. 1990 Aug;60(4):187–196. [PubMed] [Google Scholar]
  17. Farsky S. H., Walber J., Costa-Cruz M., Cury Y., Teixeira C. F., Curry Y. Leukocyte response induced by Bothrops jararaca crude venom: in vivo and in vitro studies. Toxicon. 1997 Feb;35(2):185–193. doi: 10.1016/s0041-0101(96)00135-3. [DOI] [PubMed] [Google Scholar]
  18. Flores C. A., Zappellini A., Prado-Franceschi J. Lipoxygenase-derived mediators may be involved in in vivo neutrophil migration induced by Bothrops erythromelas and Bothrops alternatus venoms. Toxicon. 1993 Dec;31(12):1551–1559. doi: 10.1016/0041-0101(93)90339-k. [DOI] [PubMed] [Google Scholar]
  19. Garcia Leme J., Hamamura L. Formation of a factor increasing vascular permeability during electrical stimulation of the saphenous nerve in rats. Br J Pharmacol. 1974 Jul;51(3):383–389. doi: 10.1111/j.1476-5381.1974.tb10673.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gutiérrez J. M., Chaves F., Bolaños R., Cerdas L., Rojans E., Arroyo O., Portilla E. Neutralization de los effectos locales del veneno de Bothrops asper por un antiveneno polivalente. Toxicon. 1981;19(4):493–500. doi: 10.1016/0041-0101(81)90007-6. [DOI] [PubMed] [Google Scholar]
  21. Gutiérrez J. M., León G., Rojas G., Lomonte B., Rucavado A., Chaves F. Neutralization of local tissue damage induced by Bothrops asper (terciopelo) snake venom. Toxicon. 1998 Nov;36(11):1529–1538. doi: 10.1016/s0041-0101(98)00145-7. [DOI] [PubMed] [Google Scholar]
  22. Gutiérrez J. M., Rojas G., Lomonte B., Gené J. A., Cerdas L. Comparative study of the edema-forming activity of Costa Rican snake venoms and its neutralization by a polyvalent antivenom. Comp Biochem Physiol C. 1986;85(1):171–175. doi: 10.1016/0742-8413(86)90069-1. [DOI] [PubMed] [Google Scholar]
  23. Gyires K., Budavári I., Fürst S., Molnár I. Morphine inhibits the carrageenan-induced oedema and the chemoluminescence of leucocytes stimulated by zymosan. J Pharm Pharmacol. 1985 Feb;37(2):100–104. doi: 10.1111/j.2042-7158.1985.tb05015.x. [DOI] [PubMed] [Google Scholar]
  24. Jancsó N., Jancsó-Gábor A., Szolcsányi J. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol Chemother. 1967 Sep;31(1):138–151. doi: 10.1111/j.1476-5381.1967.tb01984.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Joris J., Costello A., Dubner R., Hargreaves K. M. Opiates suppress carrageenan-induced edema and hyperthermia at doses that inhibit hyperalgesia. Pain. 1990 Oct;43(1):95–103. doi: 10.1016/0304-3959(90)90054-H. [DOI] [PubMed] [Google Scholar]
  26. Kamiguti A. S., Theakston R. D., Desmond H., Hutton R. A. Systemic haemorrhage in rats induced by a haemorrhagic fraction from Bothrops jararaca venom. Toxicon. 1991;29(9):1097–1105. doi: 10.1016/0041-0101(91)90207-8. [DOI] [PubMed] [Google Scholar]
  27. Lembeck F., Holzer P. Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn Schmiedebergs Arch Pharmacol. 1979 Dec;310(2):175–183. doi: 10.1007/BF00500282. [DOI] [PubMed] [Google Scholar]
  28. Lomonte B., Tarkowski A., Hanson L. A. Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model. Inflammation. 1993 Apr;17(2):93–105. doi: 10.1007/BF00916097. [DOI] [PubMed] [Google Scholar]
  29. Malucelli B. E., Mariano M. The haemorrhagic exudate and its possible relationship to neurogenic inflammation. J Pathol. 1980 Mar;130(3):193–200. doi: 10.1002/path.1711300308. [DOI] [PubMed] [Google Scholar]
  30. Maruyama M., Tanigawa M., Sugiki M., Yoshida E., Mihara H. Purification and characterization of low molecular weight fibrinolytic/hemorrhagic enzymes from snake (Bothrops jararaca) venom. Enzyme Protein. 1993;47(3):124–135. doi: 10.1159/000468668. [DOI] [PubMed] [Google Scholar]
  31. Moreira L., Gutiérrez J. M., Borkow G., Ovadia M. Ultrastructural alterations in mouse capillary blood vessels after experimental injection of venom from the snake Bothrops asper (Terciopelo). Exp Mol Pathol. 1992 Oct;57(2):124–133. doi: 10.1016/0014-4800(92)90004-u. [DOI] [PubMed] [Google Scholar]
  32. OHSAKA A., IKEZAWA H., KONDO H., KONDO S., UCHIDA N. Haemorrhagic activities of habu snake venom, and their relations to lethal toxicity, proteolytic activities and other pathological activities. Br J Exp Pathol. 1960 Oct;41:478–486. [PMC free article] [PubMed] [Google Scholar]
  33. OHSAKA A. Proteolytic activities of Habu snake venom and their separation from lethal toxicity. Jpn J Med Sci Biol. 1960 Apr;13:33–41. doi: 10.7883/yoken1952.13.33. [DOI] [PubMed] [Google Scholar]
  34. OMORI T., IWANAGA S., SUZUKI T. THE RELATIONSHIP BETWEEN THE HEMORRHAGIC AND LETHAL ACTIVITIES OF JAPANESE MAMUSHI (AGKISTRODON HALYS BLOMHOFFII) VENOM. Toxicon. 1964 Jun;15:1–4. doi: 10.1016/0041-0101(64)90027-3. [DOI] [PubMed] [Google Scholar]
  35. Osaka A., Just M., Habermann E. Action of snake venom hemorrhagic principles on isolated glomerular basement membrane. Biochim Biophys Acta. 1973 Oct 25;323(3):415–428. doi: 10.1016/0005-2736(73)90187-9. [DOI] [PubMed] [Google Scholar]
  36. Osaka A., Suzuki K., Oashi M. The spurting of erythrocytes through junctions of the vascular endothelium treated with snake venom. Microvasc Res. 1975 Sep;10(2):208–213. doi: 10.1016/0026-2862(75)90007-2. [DOI] [PubMed] [Google Scholar]
  37. Ownby C. L., Bjarnason J., Tu A. T. Hemorrhagic toxins from rattlesnake (Crotalus atrox) venom. Pathogenesis of hemorrhage induced by three purified toxins. Am J Pathol. 1978 Oct;93(1):201–218. [PMC free article] [PubMed] [Google Scholar]
  38. Ownby C. L., Colberg T. R., Odell G. V. A new method for quantitating hemorrhage induced by rattlesnake venoms: ability of polyvalent antivenom to neutralize hemorrhagic activity. Toxicon. 1984;22(2):227–233. doi: 10.1016/0041-0101(84)90023-0. [DOI] [PubMed] [Google Scholar]
  39. Perales J., Amorim C. Z., Rocha S. L., Domont G. B., Moussatché H. Neutralization of the oedematogenic activity of Bothrops jararaca venom on the mouse paw by an antibothropic fraction isolated from opossum (Didelphis marsupialis) serum. Agents Actions. 1992 Nov;37(3-4):250–259. doi: 10.1007/BF02028117. [DOI] [PubMed] [Google Scholar]
  40. Shannon J. D., Baramova E. N., Bjarnason J. B., Fox J. W. Amino acid sequence of a Crotalus atrox venom metalloproteinase which cleaves type IV collagen and gelatin. J Biol Chem. 1989 Jul 15;264(20):11575–11583. [PubMed] [Google Scholar]
  41. Teixeira C. F., Cury Y., Oga S., Jancar S. Hyperalgesia induced by Bothrops jararaca venom in rats: role of eicosanoids and platelet activating factor (PAF). Toxicon. 1994 Apr;32(4):419–426. doi: 10.1016/0041-0101(94)90293-3. [DOI] [PubMed] [Google Scholar]
  42. Toom P. M., Squire P. G., Tu A. T. Characterization of the enzymatic and biological activities of snake venoms by isoelectric focusing. Biochim Biophys Acta. 1969 May;181(1):339–341. doi: 10.1016/0005-2795(69)90262-1. [DOI] [PubMed] [Google Scholar]
  43. Trebien H. A., Calixto J. B. Pharmacological evaluation of rat paw oedema induced by Bothrops jararaca venom. Agents Actions. 1989 Mar;26(3-4):292–300. doi: 10.1007/BF01967293. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES