- Email: [email protected]
Pharmacokinetics of Bothrops erythromelas venom
528
Abstracts/Toxtcon 38 (2000) 487-595
Thalassophryne nattereri. M. Lopes-Ferreira, H. Takehara, A.M. Moura-da-Silva, I. Mota (Laborat6rio de Imunopatologia, Instituto Butantan, S~o Paulo, Brasil). Objective: Accidents by fishes of the Genus Thalassopho,ne is a serious problem in the northeast of Brazil, causing in the victims intense pain and edema followed by necrosis. Since there is no specific treatment for the envenomation by these fishes the present work aims the evaluation of a potential treatment with serumtherapy using experimental models. Methods and results: Antivenom was prepared in rabbits injected intramuscularly (i.m.) with crude venom without adjuvant. It has an ELISA titer of 1:8,192,000. Its neutralizing ability was accessed by preincubation in vitro with the venom or independent injections into Swiss mice. In order to analyze the neutralization of the lethality induced by the venom, increasing doses of the antiserum (50, 100, 200, 300 and 400 ~tl) were incubated with 364 ~tg venom (4DLs0), for 30 rain at 37°C followed by intraperitoneal (i.p.) injections into normal mice. Controls were similarly treated using venom incubated with normal rabbit serum. The animals were observed for 48 h and complete surveillance of the animals could be observed when venom was incubated with doses higher than 400 ~tl of antiserum. The EDs0 of this serum was 141.42 rag. The ability of the antivenom in neutralizing the other venom activities was analysed by independent injections of venom and antivenom into the mice. Animals were injected intradermally (i.d.) in the foot pad with 30 ~tg venom and then injected with 200 ~1 antiserum intravenously (i.v.) or i.m. 30 rain before, immediately or 15 min after. When the antiserum was injected by the i.m. route there was significant neutralization of the necrotic activity independently of the time of antiserum application but there was no effect on the nociception or edema. When the antiserum was applied i.v. there was neutralization of all toxic activities but edema in all instances. Conclusion: These results suggest that serumtherapy might be a promissing treatment for victims of accidents with T. nctttereri. The antivenom was able in neutralizing venom activities even when injected 30 min after the venom. However, the edema was not neutralized by the antiserum suggesting that the use of specific pharmacological antagonists together with serumtherapy could be necessary in order to neutralize the action of this venom. Acknowledgements" Supported by FAPESP 96/05092-3 and CNPq 520636/ 96-1.
Pharmacokinetics of Bothrops erythromelas venom. M.L. Rocha a, R.C. Valenca b, M.M. Pontes °, J.C. Modesto c, C.M.L. Vasconcelos b, E.A. Araujo b, R.M. Lirada-Silva d, M.C. Guarnieri c (aDepartamento Biologia, UEFS, Feira de Santana, BA; bDepartamento Biofisica; ~Departamento Zoologia, UFPE, Recife, PE; dDepartamento Zoologia, UFBA, Salvador, BA). Objective; To determine the pharmacokinetic parameters of B. e~vthromelas venom (BeV) in the presence and absence of the Bothrops antivenom (BA). Methods and results: BeV was labeled with NaI-131 by the Chloramine T method. Forty mice received an intravenous injection of 0.3 ml of labeled venom (12 × 106 Bq). Blood samples were collected at 1, 5, 15, 30, 60, 120, 240 or 480 rain post-injection to determine the levels of
Abstracts / Toxicon 38 (2000) 487 595
529
radioactivity. BeV showed a bicompartmental distribution in the blood of both experimental groups. The administration of Bothrops antivenom (BA) resulted in higher concentrations of venom in the blood. The distribution phase of BeV was fast, both in the absence and presence of BA (tl/2c~=5 and 8.66 min, respectively). The elimination phase was slower, with tl/2/~ = 6.08 h for BeV alone and tl/2/~=23 h for B e V + B A . The rates of transfer from the central to the tissue compartment (Kct) were 0.0704 min -1 and 0.1072 min -I for BeV and B e V + B A , respectively. The distribution constants for the tissue to the central compartment (Ktc) and for elimination (Kd) were 0.02 min 1 and 0.0077 min -1 for BeV and 0.04 min -1 and 0.0017 min -1 for B e V + B A , respectively. Chromatographic analysis of plasma samples suggested that BeV associated reversibly with plasma proteins and that the venom components formed complexes with BA that remained in the circulation for as long as 8 h after inoculation, thus explaining the increase in tl/2c~ in the B e V + B A group. Conclusions: B. erythromelas venom is rapidly distributed into tissues. In the presence of antibothropic serum, the venom components were redistributed from the tissue compartment back into the central compartment.
Toxin data bank." a database of molecular atzd biological data on toxhTs. A.M. Siqueira a' b W. Meira Jr c, A.C.M. Pereira c, S.L. Novaes b, M.M. Santoro a (aDepartamento Bioquimica e Imunologia, ICB-UFMG; bCENAPAD-MG/CO; CDepartamento Ci6ncia da Computaqfio, I C E X - U F M G , C.P. 486, 31270-910, Belo Horizonte, MG, Brazil)[email protected] Objectives: Our goal was to implement a database of molecular, structural, pharmacological and biological data on toxins of animal, plant and microbiological origins and their receptor molecules, accessible over the Internet and linked to databases already established. The purpose of the Toxin Data Bank is to act as a central information source for researchers of toxins and their receptors. Methods and results: Existing data banks were taken as models for our own implementation. The PDB format was used for the structural data. The Medline and Entrez formats were adopted for bibliographic and taxonomic data. Our data bank enables one to retrieve all the available data, or an user-defined data subset for a given toxin or toxin-receptor molecule: biological source and describing literature, 3dimensional structure, mode of action and target biological structure or agonist. We already have over 128 entries in the Toxin Data Bank. The same data cannot be easily and rapidly retrieved elsewhere since they are scattered over several nonspecialized databases. Conclusion: We have implemented, at a single Internet address, an useful and powerful tool for the retrieval and maintenance of data on toxins of biological origin and their target molecular structures. Computerized mirroring of other sources and direct and voluntary submission of data by authors or publishers will achieve the c o n t i n u o u s u p d a t e o f the T o x i n D a t a Bank. Acknowledgements: Financial support from C E N A P A D - M G / C O . Molecular modell#tg and expression of recombinant kn-bj 2, a kinin-releasing and
Abstracts/Toxtcon 38 (2000) 487-595
Thalassophryne nattereri. M. Lopes-Ferreira, H. Takehara, A.M. Moura-da-Silva, I. Mota (Laborat6rio de Imunopatologia, Instituto Butantan, S~o Paulo, Brasil). Objective: Accidents by fishes of the Genus Thalassopho,ne is a serious problem in the northeast of Brazil, causing in the victims intense pain and edema followed by necrosis. Since there is no specific treatment for the envenomation by these fishes the present work aims the evaluation of a potential treatment with serumtherapy using experimental models. Methods and results: Antivenom was prepared in rabbits injected intramuscularly (i.m.) with crude venom without adjuvant. It has an ELISA titer of 1:8,192,000. Its neutralizing ability was accessed by preincubation in vitro with the venom or independent injections into Swiss mice. In order to analyze the neutralization of the lethality induced by the venom, increasing doses of the antiserum (50, 100, 200, 300 and 400 ~tl) were incubated with 364 ~tg venom (4DLs0), for 30 rain at 37°C followed by intraperitoneal (i.p.) injections into normal mice. Controls were similarly treated using venom incubated with normal rabbit serum. The animals were observed for 48 h and complete surveillance of the animals could be observed when venom was incubated with doses higher than 400 ~tl of antiserum. The EDs0 of this serum was 141.42 rag. The ability of the antivenom in neutralizing the other venom activities was analysed by independent injections of venom and antivenom into the mice. Animals were injected intradermally (i.d.) in the foot pad with 30 ~tg venom and then injected with 200 ~1 antiserum intravenously (i.v.) or i.m. 30 rain before, immediately or 15 min after. When the antiserum was injected by the i.m. route there was significant neutralization of the necrotic activity independently of the time of antiserum application but there was no effect on the nociception or edema. When the antiserum was applied i.v. there was neutralization of all toxic activities but edema in all instances. Conclusion: These results suggest that serumtherapy might be a promissing treatment for victims of accidents with T. nctttereri. The antivenom was able in neutralizing venom activities even when injected 30 min after the venom. However, the edema was not neutralized by the antiserum suggesting that the use of specific pharmacological antagonists together with serumtherapy could be necessary in order to neutralize the action of this venom. Acknowledgements" Supported by FAPESP 96/05092-3 and CNPq 520636/ 96-1.
Pharmacokinetics of Bothrops erythromelas venom. M.L. Rocha a, R.C. Valenca b, M.M. Pontes °, J.C. Modesto c, C.M.L. Vasconcelos b, E.A. Araujo b, R.M. Lirada-Silva d, M.C. Guarnieri c (aDepartamento Biologia, UEFS, Feira de Santana, BA; bDepartamento Biofisica; ~Departamento Zoologia, UFPE, Recife, PE; dDepartamento Zoologia, UFBA, Salvador, BA). Objective; To determine the pharmacokinetic parameters of B. e~vthromelas venom (BeV) in the presence and absence of the Bothrops antivenom (BA). Methods and results: BeV was labeled with NaI-131 by the Chloramine T method. Forty mice received an intravenous injection of 0.3 ml of labeled venom (12 × 106 Bq). Blood samples were collected at 1, 5, 15, 30, 60, 120, 240 or 480 rain post-injection to determine the levels of
Abstracts / Toxicon 38 (2000) 487 595
529
radioactivity. BeV showed a bicompartmental distribution in the blood of both experimental groups. The administration of Bothrops antivenom (BA) resulted in higher concentrations of venom in the blood. The distribution phase of BeV was fast, both in the absence and presence of BA (tl/2c~=5 and 8.66 min, respectively). The elimination phase was slower, with tl/2/~ = 6.08 h for BeV alone and tl/2/~=23 h for B e V + B A . The rates of transfer from the central to the tissue compartment (Kct) were 0.0704 min -1 and 0.1072 min -I for BeV and B e V + B A , respectively. The distribution constants for the tissue to the central compartment (Ktc) and for elimination (Kd) were 0.02 min 1 and 0.0077 min -1 for BeV and 0.04 min -1 and 0.0017 min -1 for B e V + B A , respectively. Chromatographic analysis of plasma samples suggested that BeV associated reversibly with plasma proteins and that the venom components formed complexes with BA that remained in the circulation for as long as 8 h after inoculation, thus explaining the increase in tl/2c~ in the B e V + B A group. Conclusions: B. erythromelas venom is rapidly distributed into tissues. In the presence of antibothropic serum, the venom components were redistributed from the tissue compartment back into the central compartment.
Toxin data bank." a database of molecular atzd biological data on toxhTs. A.M. Siqueira a' b W. Meira Jr c, A.C.M. Pereira c, S.L. Novaes b, M.M. Santoro a (aDepartamento Bioquimica e Imunologia, ICB-UFMG; bCENAPAD-MG/CO; CDepartamento Ci6ncia da Computaqfio, I C E X - U F M G , C.P. 486, 31270-910, Belo Horizonte, MG, Brazil)[email protected] Objectives: Our goal was to implement a database of molecular, structural, pharmacological and biological data on toxins of animal, plant and microbiological origins and their receptor molecules, accessible over the Internet and linked to databases already established. The purpose of the Toxin Data Bank is to act as a central information source for researchers of toxins and their receptors. Methods and results: Existing data banks were taken as models for our own implementation. The PDB format was used for the structural data. The Medline and Entrez formats were adopted for bibliographic and taxonomic data. Our data bank enables one to retrieve all the available data, or an user-defined data subset for a given toxin or toxin-receptor molecule: biological source and describing literature, 3dimensional structure, mode of action and target biological structure or agonist. We already have over 128 entries in the Toxin Data Bank. The same data cannot be easily and rapidly retrieved elsewhere since they are scattered over several nonspecialized databases. Conclusion: We have implemented, at a single Internet address, an useful and powerful tool for the retrieval and maintenance of data on toxins of biological origin and their target molecular structures. Computerized mirroring of other sources and direct and voluntary submission of data by authors or publishers will achieve the c o n t i n u o u s u p d a t e o f the T o x i n D a t a Bank. Acknowledgements: Financial support from C E N A P A D - M G / C O . Molecular modell#tg and expression of recombinant kn-bj 2, a kinin-releasing and