title: Biochemical and pharmacological characterization of a toxic fraction and its cytotoxin-like component isolated from Russell's viper (Daboia russelii russelii) venom.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rupamoni
authors.initials: R
authors.lastname: Thakur
authors.affiliation: Division of Pharmaceutical Technology, Defence Research Laboratory, Tezpur 784 001, Assam, India.
authors.forename: Pronobesh
authors.initials: P
authors.lastname: Chattopadhyay
authors.affiliation: Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, School of Science, Tezpur University, Tezpur-784 028, Assam, India.
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D000997:Antivenins / Q000494:pharmacology; D003603:Cytotoxins / Q000009:adverse effects* / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008978:Mollusk Venoms / Q000009:adverse effects* / Q000494:pharmacology*; D017840:Daboia / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014757:Viper Venoms / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D000997:Antivenins; D003603:Cytotoxins; D005343:Fibrinolytic Agents; D015850:Interleukin-6; D008978:Mollusk Venoms; D014409:Tumor Necrosis Factor-alpha; D014757:Viper Venoms; D016753:Interleukin-10
keywords: Cytotoxin; Hyperfibrinogenomia; Inflammatory cytokines; Multiple organ dysfunction; Prey immobilization; Protease; Russell's viper venom