Molecular and Cellular Biochemistry

, Volume 282, Issue 1, pp 147–155

Strong myotoxic activity of Trimeresurus malabaricus venom: Role of metalloproteases

  • C. D. Raghavendra Gowda
  • R. Rajesh
  • A. Nataraju
  • B. L. Dhananjaya
  • A. R. Raghupathi
  • T. V. Gowda
  • B. K. Sharath
  • B. S. Vishwanath
Article

DOI: 10.1007/s11010-006-1738-3

Cite this article as:
Gowda, C.D.R., Rajesh, R., Nataraju, A. et al. Mol Cell Biochem (2006) 282: 147. doi:10.1007/s11010-006-1738-3

Abstract

Trimeresurus malabaricus is an endemic snake found in the Southern region of Western Ghats section of India along with the more widely distributed species like Naja naja and Daboia russelii. T. malabaricus venom is not lethal when injected (i.p.) up to 20 mg/kg body weight in mice, but causes extensive local tissue degeneration. N. naja and D. russelii are highly toxic (i.p.) with minimum local tissue damage in experimental mice. In this study a comparative analysis of local tissue damage of T. malabaricus venom is made with N. naja and D. russelii snake venoms of the Southern regions of Western Ghats. T. malabaricus venom exhibits caseinolytic activity 16 and 24 times more than N. naja and D. russelii venom. Inhibition studies with specific protease inhibitors reveal that the major proteases belong to metalloproteases. T. malabaricus venom hydrolyses gelatin and induces strong hemorrhagic activity in mice. Both N. naja and D. russelii fail to hydrolyze gelatin even at very high concentration and did not induce any hemorrhagic activity. With D. russelii venom small hemorrhagic spot was observed at the site of injection. The hemorrhagic activity of T. malabaricus venom is completely neutralized by metalloprotease inhibitors and not by serine protease inhibitor. The i.m. injection of T. malabaricus venom causes extensive degradation of muscle tissue within 24 h. The light microscopic observation of muscle tissue showed congestion of blood vessels and hemorrhage at the early stage followed by extensive necrosis of muscle fibers. The elevated levels of serum CK and LDH activity further supported the muscle degeneration. Such pathological symptoms were not seen with N. naja and D. russelii snake venom. The hemorrhagic and the muscle necrosis was completely neutralized by metalloprotease inhibitors and not by serine protease inhibitor strongly suggests that the major toxin component in the T. malabaricus venom is metalloprotease and its activity can be easily neutralized using chelating agents and its use in the first aid as chelation therapy is beneficial.

Key words

gelatinasehemorrhagemetalloproteasemyotoxicitysouthern region of Western GhatsTrimeresurus malabaricus

Abbreviation

C

degree Celsius

cm

centimeter

g

gram

h

hour(s)

i.m.

intramuscular

i.p.

intraperitonial

kg

kilogram

LD50

lethal dose 50

μg

microgram

μM

micromolar

min

minute

ml

milliliter

mM

millimolar

nmol

nanomole

%

percentage

s

second(s)

s.c.

subcutaneous

S.E.M.

standard error mean

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • C. D. Raghavendra Gowda
    • 1
  • R. Rajesh
    • 1
  • A. Nataraju
    • 1
  • B. L. Dhananjaya
    • 1
  • A. R. Raghupathi
    • 2
  • T. V. Gowda
    • 1
  • B. K. Sharath
    • 3
  • B. S. Vishwanath
    • 1
  1. 1.Department of Studies in BiochemistryMysore UniversityManasagangotri, MysoreIndia
  2. 2.Department of PathologyGovernment Medical CollegeMysoreIndia
  3. 3.Department of Studies in BioscienceMysore UniversityHassanIndia