Biochemical and pharmacological characterization of a toxic fraction and its cytotoxin-like component isolated from Russell's viper (Daboia russelii russelii) venom.

Thakur, Rupamoni; Chattopadhyay, Pronobesh; Mukherjee, Ashis K

Thakur, Rupamoni; Chattopadhyay, Pronobesh; Mukherjee, Ashis K.

Afiliación

Thakur R; Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Science, Tezpur University, Tezpur-784 028, Assam, India. Electronic address: rupat@tezu.ernet.in.
Chattopadhyay P; Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur 784 001, Assam, India.
Mukherjee AK; Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Science, Tezpur University, Tezpur-784 028, Assam, India.

Comp Biochem Physiol C Toxicol Pharmacol ; 168: 55-65, 2015 Feb.

Article en En | MEDLINE | ID: mdl-25500420

RESUMEN

The pathophysiological significance of a toxic fraction (GF-VI DEAE-II) isolated from Russell's viper venom (RVV) is characterized. GF-VI DEAE-II represents 1.6% of the total RVV protein and it comprises of a 27.6kDa minor component (RP-I) (0.04%, w/w) and a major 6.6kDa non-enzymatic peptide (1.11%, w/w), named Rusvitoxin. The LC-MS/MS analysis of RP-I showed its identity to snake venom serine proteases, whereas Rusvitoxin demonstrated its close identity with snake venom three finger toxins, cytotoxins and cardiotoxins particularly from Naja sp. GF-VI DEAE-II was found to be non-cytotoxic to the tested mammalian cancer cells and non-hemolytic; nevertheless, it demonstrated α-fibrin(ogen)ase activity and in vivo toxicity in BALB/c mice with an LD50 (i.p.) of 2.3mg/kg. GF-VI DEAE-II induced lethargy and hind-leg paralysis in mice within 10min of i.p. injection. GF-VI DEAE-II induced hyperfibrinogenomia, and significantly altered (p<0.05) the plasma levels of factor X, pro- and anti-inflammatory cytokines viz. TNF-α, IL-6 and IL-10 in treated mice. Histological observations of tissues and biochemical properties of serum from GF-VI DEAE-II-treated mice suggested multiple organ dysfunctions. Conversely, Rusvitoxin at a dose of 5mg/kg did not induce toxicity in BALB/c mice. At 1:15 (antigen: antivenom, w/w) ratio, commercially polyvalent and monovalent antivenoms neutralized more than 80% of the fibrinolytic and anticoagulant activities of GF-VI DEAE-II. The present study suggests the significant role of GF-VI DEAE-II in RVV-induced pathogenesis in victim/prey.

Asunto(s)

Citotoxinas/efectos adversos; Citotoxinas/farmacología; Daboia/metabolismo; Venenos de Moluscos/efectos adversos; Venenos de Moluscos/farmacología; Venenos de Víboras/efectos adversos; Venenos de Víboras/farmacología; Animales; Anticoagulantes/metabolismo; Antivenenos/farmacología; Fibrinolíticos/metabolismo; Interleucina-10/metabolismo; Interleucina-6/metabolismo; Ratones; Ratones Endogámicos BALB C; Factor de Necrosis Tumoral alfa/metabolismo

Palabras clave

Cytotoxin; Hyperfibrinogenomia; Inflammatory cytokines; Multiple organ dysfunction; Prey immobilization; Protease; Russell's viper venom

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Víboras / Daboia / Citotoxinas / Venenos de Moluscos Límite: Animals Idioma: En Revista: Comp Biochem Physiol C Toxicol Pharmacol Asunto de la revista: FARMACOLOGIA / TOXICOLOGIA Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos

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