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In Vivo Effects of Bothrops jararaca Venom on Metabolic Profile and on Muscle Protein Metabolism in Rats

This study investigated the in vivo effects of the Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, on muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference, indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.

Received May 27, 2008. Accepted for publication July 20, 2008.

Acknowledgments: We thank Luiz Onivaldo Bizuti, Elza A. Filippin, Dr. Amanda Baviera, and Dr. Victor Dias Galbán.

Financial support: This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp 04/02674-0) and Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq; 305847/06-6 and 300440/05-7). During this study, Dawit A. P. Gonçalves and Érico V. C. M. Silva received fellowship from CNPq and PIBIC/CNPq, respectively.

^* Address correspondence to Luiz Carlos C. Navegantes, Department of Physiology, School of Medicine of Ribeirão Preto, USP, 14049-900, Ribeirão Preto, SP, Brazil. E-mail: navegantes{at}fmrp.usp.br

Authors’ addresses: Dawit A. P. Gonçalves, Flávia A. Graça, Eduardo C. Lira, and Neusa M. Zanon, Department of Physiology, School of Medicine of Ribeirão Preto, USP, 14049-900, Ribeirão Preto, SP, Brazil, Tel: 55-16-36023182, E-mails: dawitapg{at}yahoo.com.br, flaviaapgraca{at}yahoo.com.br, eduardoclira{at}gmail.com, and neusam{at}fmrp.usp.br. Érico V. C. M. Silva, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, School of Medicine of Botucatu, UNESP, 18618-000, Botucatu, SP, Brazil, Tel: 55-14-38116256, E-mail: ericovcms{at}hotmail.com. Glória E. Mendes and Emmanuel A. Burdmann, Department of Molecular Biology and Division of Nephrology, School of Medicine of São José do Rio Preto, 15090-000, São José do Rio Preto, SP, Brazil, Tel/Fax: 55-17-32015886 and 55-17-32015712, E-mails: labrim{at}famerp.br and burdmann{at}famerp.br. Renato H. Migliorini (in memoriam), Isis C. Kettelhut, and Luiz C. C. Navegantes, Department of Physiology and Biochemistry and Immunology, School of Medicine of Ribeirão Preto, USP, 14049-900, Ribeirão Preto, SP, Brazil, Tel: 55-16-36023212, E-mails: idckette{at}fmrp.usp.brnavegantes{at}fmrp.usp.br.