THE DISTRIBUTION AND ELIMINATION OF Bothrops erythromelas VENOM LABELED WITH 131 I AFTER INTRAVENOUS INJECTION IN MICE

THESIS: M. L. Rocha submitted this dissertation to obtain the degree of Master of Biophysics, publicly examined at the Biophysics and Radiobiology Department of the Federal University of Pernambuco, Recife, Brazil, in February 1998.

Advisor: Dra. Míriam Camargo Guarnieri

ABSTRACT. Pharmacokinetic studies can be used to study the systemic effects of snake venoms and to develop standard serotherapy protocols for envenomation. Bothrops erythromelas is probably responsible for most of the snakebite in Pernambuco. The objective of this study was to investigate the pharmacokinetics of B. erythromelas venom (BeV) in mice, and to evaluate the efficacy of bothropic antivenom (BA). BeV showed bicompartmental distribution in the blood of the experimental animals. The distribution phase of BeV was rapid, both in the absence and presence of BA (t½;a = 8.66 and 5 min, respectively). The elimination phase was slower (t½;b = 6.08 h for BeV alone and t½;b = 23 h for BeV+BA). The transfer rates from the central compartment to the peripheral compartment were 0.0704 minand 0.1072 minfor BeV and BeV+/BA, respectively. The distribution rates from both the tissue compartment to the central compartment and for elimination were 0.02 minand 0.0077 minfor BeV, and 0.04 minand 0.0017 minfor BeV+BA, respectively. These results indicate that after intravenous injection, B. erythromelas venom was rapidly distributed into the tissues. Use of bothropic antivenom resulted in a significant increase in concentration of venom in the plasma, suggesting that toxins were redistributed from the peripheral compartment back into the central compartment. Chromatographic analysis of plasma samples collected at different times from animals inoculated with BeV and BeV+BA suggest that BeV associates reversibly with plasma proteins and in the presence of BA, it forms complexes that remain in the circulation until as much as 8 h after inoculation, thereby explaining the increase for t½;a in the BeV+BA group. BeV distribution in the organs of mice showed that the liver, kidneys, and spleen were responsible for venom catabolism in both groups of animals, specially during the first 15 min. The liver considered the principal organ responsible for venom degradation, showed maximum BeV concentration 5 min post-injection (22% for BeV and 19.8% for BeV+BA, respectively). The lungs and heart of the experimental animals showed a distribution profile of BeV similar to that of the blood. The maximum concentration of BeV (5.2%) in the kidneys was observed 5 min post-injection in BeV+BA group. The BeV animals showed the maximum concentration of 6% 15 min after inoculation. In the gastrointestinal tract, the small intestine, and stomach contained most of the bound BeV during the period 1 to 15 min in BeV and 30 to 120 min in BeV+BA animals. Most of the radioactivity was detected in the gastrointestinal contents rather than in the tissues themselves, indicating that the stomach and intestines actively participate in the elimination and/or metabolism of venom. The administration of BA significantly reduced the concentration of venom in the stomach and small intestine. Clearance through the kidneys occurred primarily during the first 12 h post-injection (50%), rising to only 56% after 48 h. These results indicate that the venom clearance occurs by both urinary and gastrointestinal tracts.

CORRESPONDENCE TO:

M. L. ROCHA - Departamento de Zoologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rego 1235, Cidade Universitária, CEP 50670-901, Recife, Pernambuco, Brasil.

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Publication Dates

• Publication in this collection
  16 Apr 1999
• Date of issue
  1999