Skip to main content
SpringerLink
Log in

Pharmacological Study of Edema and Myonecrosis in Mice Induced by Venom of the Bushmaster Snake (Lachesis muta muta) and Its Basic Asp49 Phospholipase A2 (LmTX-I)

  • Published:
The Protein Journal Aims and scope Submit manuscript

Abstract

Previous in vitro studies show that Lachesis muta venom and its purified Asp49 phospholipase A2, named as LmTX-I, display potent neurotoxic and myotoxic activities. Here, an in vivo study was conducted to investigate some pharmacological effects of the venom or its LmTX-I toxin, after intra-muscular injection in tibialis anterior (TA) and following subplantar injection in hind paws of mice. Findings showed that LmTX-I increased plasma creatine kinase activity and produced strong myonecrosis and inflammatory reactions in TA muscle. In addition to these effects, the venom also induced intense local hemorrhage. Pre-treatment of the venom with EDTA (5 mM) significantly inhibited the edema and hemorrhage. Histological examination showed that L. muta venom caused inner dermal layer thickening in the pad hind paw. In addition, there was marked inflammatory cell infiltration, particularly of neutrophils, and hemorrhage. LmTX-I also demonstrated edema-forming activity, which was inhibited by pretreatment with indomethacin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

CK:

Creatine kinase

EDTA:

Ethylenediaminetetracetic acid

HPLC:

High performance liquid chromatography

i.m.:

Intramuscular

LmTX-I:

Lachesis muta toxin I

TA muscle:

Tibialis anterior muscle

References

  1. Barros SF, Friedlanskaia I, Petricevich BL, Kipnis T (1998) Mediators Inflamm 7:339–346

    Article  CAS  Google Scholar 

  2. Calhoun W, Yu J, Sung A, Chau TT, Marshall LA, Weichman BM, Carlson RP (1989) Agents Actions 27:418–421

    Article  CAS  Google Scholar 

  3. Chaves F, León G, Alvarado VH, Gutiérrez JM (1998) Toxicon 36:1861–1869

    Article  CAS  Google Scholar 

  4. Chaves F, Teixeira CF, Gutiérrez JM (2005) Toxicon 45:171–178

    Article  CAS  Google Scholar 

  5. Chioato L, De Oliveira AH, Ruller R, Sa JM, Ward RJ (2002) Biochem J 366:971–976

    CAS  Google Scholar 

  6. Campbell JA, Lamar WW, Greene H (2003) The venomous reptiles of the Western hemisphere. Cornell University, New York

    Google Scholar 

  7. Cirino G, Peers SH, Wallace JL, Flower RJ (1989) Eur J Pharmacol 166:505–510

    Article  CAS  Google Scholar 

  8. Damico DCS, Bueno LGF, Rodrigues-Simioni L, Marangoni S, Cruz-Höfling MA, Novello JC (2005) Toxicon 46:222–229

    Article  CAS  Google Scholar 

  9. Damico DCS, Lilla S, de Nucci G, Ponce-Soto LA, Winck FV, Novello JC, Marangoni S (2005) Biochim Biophys Acta 1726:75–86

    CAS  Google Scholar 

  10. Damico DCS, Bueno LGF, Rodrigues-Simioni L, Marangoni S, Cruz-Höfling MA, Novello JC (2006) Toxicon 47:759–765

    Article  CAS  Google Scholar 

  11. Dennis EA (1994) J Biol Chem 269:13057–13060

    CAS  Google Scholar 

  12. Farsky SHP, Walber J, Costa-Cruz M, Cury Y, Teixeira CFP (1997) Toxicon 35:185–193

    Article  CAS  Google Scholar 

  13. Francis B, Gutiérrez JM, Lomonte B, Kaiser II (1991) Biophysics 284:1587–1594

    Google Scholar 

  14. Fuly AL, de Miranda ALP, Zingali RB, Guimarães JA (2002) Biochem Pharmacol 63:1589–1597

    Article  CAS  Google Scholar 

  15. Gutiérrez JM, Lomonte B (1995) Toxicon 33:1405–1424

    Article  Google Scholar 

  16. Gutiérrez JM, Ownby CL (2003) Toxicon 42:915–931

    Article  Google Scholar 

  17. Gutiérrez JM, Rojas G, Lomonte B, Gené JA, Cerdas L (1986) Comp Biochem Physiol 85C:171–175

    Google Scholar 

  18. Gutiérrez JM, Rucavado A (2000) Biochimie 82:841–845

    Article  Google Scholar 

  19. Harris JB, Cullen MJ (1990) Electron Microsc Rev 3:183–211

    Article  CAS  Google Scholar 

  20. Kaiser II, Gutiérrez JM, Plummer D, Aird SD, Odell GV (1990) Arch Biochem Biophys 278:319–325

    Article  CAS  Google Scholar 

  21. Kini RM (2003) Toxicon 42:827–840

    Article  CAS  Google Scholar 

  22. Lomonte B, Moreno E, Tarkowski A, Hanson LA, Maccarana M (1994) J Biol Chem 269:29867–29873

    CAS  Google Scholar 

  23. Maraganore JM, Heinrikson RL (1986) J Biol Chem 261:4797–4804

    CAS  Google Scholar 

  24. Murakami M, Kambe T, Shimbara S, Yamamoto S, Kuwata H, Kudo I (1999) J Biol Chem 274:29927–29936

    Article  CAS  Google Scholar 

  25. Neto HS, Marques MJ (2005) Toxicon 46:814–819

    Article  Google Scholar 

  26. Nuñez CE, Angulo Y, Lomote B (2001) Toxicon 39:1587–1594

    Article  Google Scholar 

  27. Queiroz LS, Marques MJ, Neto HS (2002) Toxicon 40:1483–1486

    Article  Google Scholar 

  28. Ran Y, Zheng S, Tu AT (1988) Chem Res Toxicol 1:337–342

    Article  CAS  Google Scholar 

  29. Rojas G, Gutiérrez JM, Gené JA, Gómez M, Cerdas L (1987) Rev Biol Trop 35:59–67

    CAS  Google Scholar 

  30. Rosenthal R, Meier J, Koelz A, Muller C, Wegmann W, Vogelbach P (2002) Toxicon 40:217–220

    Article  CAS  Google Scholar 

  31. Sánchez EF, Magalhães A, Diniz CR (1987) Toxicon 25:611–619

    Article  Google Scholar 

  32. Sánchez EF, Magalhães A, Mandelbaum FR, Diniz CR (1991) Biochim Biophys Acta 1074:347–356

    Google Scholar 

  33. Sánchez EF, Costa MIE, Chavez-Olórtegui C, Assakura MT, Mandelbaum FR, Diniz CR (1995) Toxicon 33:1653–1667

    Article  Google Scholar 

  34. Sánchez EF, Cordeiro MN, de Oliveira EB, Juliano L, Prado ES, Diniz CR (1995) Toxicon 33:1061–1069

    Article  Google Scholar 

  35. Selistre de Araújo HS, White SP, Ownby CL (1996) Arch Biochem Biophys 326:21–30

    Article  Google Scholar 

  36. Teixeira CFP, Landucci ECT, Antunes E, Chacur M, Cury Y (2003) Toxicon 42:947–962

    Article  CAS  Google Scholar 

  37. Vishwanath BS, Kini RM, Gowda TV (1987) Toxicon 25:501–515

    Article  CAS  Google Scholar 

  38. Vishwanath BS, Fawzy AA, Franson RC (1988) Inflammation 12:549–561

    Article  CAS  Google Scholar 

  39. Wang JP, Teng CM (1990) Eur J Pharmacol 190:347–354

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The author thanks my mother Adelina Ribeiro da Silva for taking care of my newly born baby while I revised this article and Paulo A. Baldasso for technical help. This work was supported by CNPq (Conselho Nacional de Pesquisa Científica e Tecnológica) and FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo). D.C·S.D. is supported by a research fellowship from CNPq. M.A.C·H. is an I-A Research Fellow from CNPq.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), P. O. Box 6109, CEP 13083-970, Campinas, SP, Brazil

    Daniela C. S. Damico, Andrana K. Calgarotto & Sérgio Marangoni

  2. Department of Histology and Embryology, Institute of Biology, State University of Campinas (UNICAMP), P. O. Box 6109, CEP 13083-970, Campinas, SP, Brazil

    Maria Alice da Cruz Höfling & Marta B. Leonardo

  3. Department of Pharmacology, Faculty of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil

    Mariana Cintra

  4. Department of Chemistry, Federal University of Amazonas (UFAM), Manaus, AM, Brazil

    Saulo L. da Silva

Authors
  1. Daniela C. S. Damico
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Alice da Cruz Höfling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariana Cintra
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marta B. Leonardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrana K. Calgarotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Saulo L. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sérgio Marangoni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Alice da Cruz Höfling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Damico, D.C.S., da Cruz Höfling, M.A., Cintra, M. et al. Pharmacological Study of Edema and Myonecrosis in Mice Induced by Venom of the Bushmaster Snake (Lachesis muta muta) and Its Basic Asp49 Phospholipase A2 (LmTX-I). Protein J 27, 384–391 (2008). https://doi.org/10.1007/s10930-008-9148-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10930-008-9148-x

Keywords

Search

Navigation