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LIVER DYSFUNCTION IN PATIENTS BITTEN BY BOTHROPS AND CROTALUS SNAKES IN BOTUCATU (STATE OF SÃO PAULO) BRAZIL:EXPERIMENTAL HEPATIC STUDY IN WISTAR RATS INOCULATED WITH CROTALUS DURISSUS TERRIFICUS (LAURENTI, 1768) VENOM

THESIS: B. Barraviera submitted this dissertation for the degree of Associate Professor publicly examined at the Department of Tropical Medicine of the School of Medicine of Botucatu - São Paulo State University - Brazil in 1993.

ABSTRACT. Thirty-two patients bitten by venomous snakes in Botucatu (State of São Paulo, Brazil), sixteen by Bothrops spp. and sixteen by Crotalus durissus terrificus were studied. The group comprised thirty males and two females, ranging from eight to sixty-three years of age (mean 33 ± 15). Leukocytosis with neutrophilia and lymphopenia, increase of mucoproteins and C-reactive protein, decrease of total serum protein and albumin, were observed on the first day after the accident. The alterations were generally more intense in patients bitten by Crotalus durissus terrificus than by Bothrops spp. Bromsulphalein tests were increased in the majority of patients bitten by Crotalus durissus terrificus. The correlation coefficient of Spearman was positive between bromsulphalein tests and alanine aminotransferase levels, and between alanine aminotransferase and aspartate aminotransferase levels only in the Crotalus group. The only patient who died, was bitten by Crotalus durissus terrificus and showed hydropic degeneration and mitochondrial injury in the liver. It is concluded that these snakebite envenomations closely resemble an acute trauma, inducing a typical acute-phase response and the hepatic damage may have been caused by at least two possible mechanisms: venom effect on liver mitochondria and/or cytokine effects on hepatocyte (1,2).

Wistar rats were experimentally inoculated intraperitoneally with Crotalus durissus terrificus venom and antivenom. The animals were divided into 4 groups: group 1: inoculated only with saline; group 2: inoculated with 0.5 ml anti-Crotalus venom produced by the Instituto Butantan; group 3: inoculated with Crotalus durissus terrificus venom (120 µg of venom to each 100 g of rat weight); group 4: inoculated with venom and immediately after with antivenom (doses according to groups 2 and 3). Forty-eight hours after inoculation, all animals were sacrificed and whole blood was collected to evaluate creatine kinase (CK), dehydrogenase lactic (DHL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymatic activities. Liver samples were collected for electron microscopy (EM). ALT and AST levels increased from groups 1 to 4. CK and DHL levels increased from groups 1 to 3; group 4 showed values between groups 2 and 3. Liver electron microscopy showed nucleus with loss of sharp chromatin details and cytoplasm flocculent aspect of cytoplasm. Mitochondria were enlarged with damage and loss of the matrix and cristae. Hepatic damage might have been caused by the venom effect on hepatocyte. Inoculated antivenom contributed to the deterioration of the hepatic function by increasing ALT and AST.

REFERENCES

01 BARRAVIERA B. Acute-phase response in snake bite. Toxicon, 1994, 32, 861-2.

02 BARRAVIERA B., COELHO KYR., CURI PR., MEIRA DA. Liver dysfunction in patients bitten by Crotalus durissus terrificus (Laurenti, 1768) snakes in Botucatu (State of São Paulo - Brazil). Rev. Inst. Med. Trop. São Paulo, 1995, 37, 63-70.

CORRESPONDENCE TO:

B. BARRAVIERA - Departamento de Doenças Tropicais e Diagnóstico por Imagem - Faculdade de Medicina de Botucatu - Campus de Botucatu - UNESP - CEP 18.618-000 - Botucatu - São Paulo - Brasil.

Publication Dates

  • Publication in this collection
    11 Jan 1999
  • Date of issue
    1995
Centro de Estudos de Venenos e Animais Peçonhentos - CEVAP, Universidade Estadual Paulista - UNESP Caixa Postal 577, 18618-000 Botucatu SP Brazil, Tel. / Fax: +55 14 3814-5555 | 3814-5446 | 3811-7241 - Botucatu - SP - Brazil
E-mail: jvat@cevap.org.br