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Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

Bhattacharya S, Chakraborty M, Mukhopadhyay P, Kundu PP, Mishra R - PLoS Negl Trop Dis (2014)

Bottom Line: Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required.Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Calcutta, Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India.

ABSTRACT

Background: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.

Methodology/principal findings: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.

Conclusions/significance: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

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Neutralization of hemolysis activity and hemorrhagic activity of venom by normal ASVS and released ASVS.(A) Dose dependent hemolytic activity of Naja naja venom on HRBC (B): Dose dependent protective efficacy of normal ASVS against Naja naja venom induced hemolysis. (C): Dose dependent protective efficacy of released ASVS against Naja naja venom induced hemolysis. (D): Comparison of anti-hemolytic activity of normal ASVS and released ASVS on Naja naja venom induced hemolysis. (E) Effect of normal ASVS and released ASVS on LDH level of HRBC hemolysate. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. * Venom control vs normal ASVS, released ASVS. (Fi) Hemorrhagic activity of Daboia russelii venom; (Fii) Neutralization of hemorrhagic activity of Daboia russelii venom by released ASVS from alginate beads.
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pntd-0003039-g004: Neutralization of hemolysis activity and hemorrhagic activity of venom by normal ASVS and released ASVS.(A) Dose dependent hemolytic activity of Naja naja venom on HRBC (B): Dose dependent protective efficacy of normal ASVS against Naja naja venom induced hemolysis. (C): Dose dependent protective efficacy of released ASVS against Naja naja venom induced hemolysis. (D): Comparison of anti-hemolytic activity of normal ASVS and released ASVS on Naja naja venom induced hemolysis. (E) Effect of normal ASVS and released ASVS on LDH level of HRBC hemolysate. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. * Venom control vs normal ASVS, released ASVS. (Fi) Hemorrhagic activity of Daboia russelii venom; (Fii) Neutralization of hemorrhagic activity of Daboia russelii venom by released ASVS from alginate beads.

Mentions: In vitro hemolysis of RBC was increased dose dependently after Naja naja venom incubation (2.5 µg–40 µg) as was observed from hemoglobin concentration of sample supernatant. The median hemolytic dose of Naja naja venom was found to be 17.45 µg in 20% RBC solution (Fig. 4A). Released ASVS dose dependently (2.5 µg–50 µg) neutralized the hemolytic activity of Naja naja venom (10 µg) significantly. The median neutralization dose of normal ASVS and released ASVS hemolytic activity of Naja naja venom was found to be 12.5 µg and 12.05 µg respectively (Fig. 4B, 4C). The neutralization capacity of hemolytic activity for released ASVS did not show any significant alteration as compared with normal ASVS in a similar 25 µg dose (Fig. 4D).


Viper and cobra venom neutralization by alginate coated multicomponent polyvalent antivenom administered by the oral route.

Bhattacharya S, Chakraborty M, Mukhopadhyay P, Kundu PP, Mishra R - PLoS Negl Trop Dis (2014)

Neutralization of hemolysis activity and hemorrhagic activity of venom by normal ASVS and released ASVS.(A) Dose dependent hemolytic activity of Naja naja venom on HRBC (B): Dose dependent protective efficacy of normal ASVS against Naja naja venom induced hemolysis. (C): Dose dependent protective efficacy of released ASVS against Naja naja venom induced hemolysis. (D): Comparison of anti-hemolytic activity of normal ASVS and released ASVS on Naja naja venom induced hemolysis. (E) Effect of normal ASVS and released ASVS on LDH level of HRBC hemolysate. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. * Venom control vs normal ASVS, released ASVS. (Fi) Hemorrhagic activity of Daboia russelii venom; (Fii) Neutralization of hemorrhagic activity of Daboia russelii venom by released ASVS from alginate beads.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125299&req=5

pntd-0003039-g004: Neutralization of hemolysis activity and hemorrhagic activity of venom by normal ASVS and released ASVS.(A) Dose dependent hemolytic activity of Naja naja venom on HRBC (B): Dose dependent protective efficacy of normal ASVS against Naja naja venom induced hemolysis. (C): Dose dependent protective efficacy of released ASVS against Naja naja venom induced hemolysis. (D): Comparison of anti-hemolytic activity of normal ASVS and released ASVS on Naja naja venom induced hemolysis. (E) Effect of normal ASVS and released ASVS on LDH level of HRBC hemolysate. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. * Venom control vs normal ASVS, released ASVS. (Fi) Hemorrhagic activity of Daboia russelii venom; (Fii) Neutralization of hemorrhagic activity of Daboia russelii venom by released ASVS from alginate beads.
Mentions: In vitro hemolysis of RBC was increased dose dependently after Naja naja venom incubation (2.5 µg–40 µg) as was observed from hemoglobin concentration of sample supernatant. The median hemolytic dose of Naja naja venom was found to be 17.45 µg in 20% RBC solution (Fig. 4A). Released ASVS dose dependently (2.5 µg–50 µg) neutralized the hemolytic activity of Naja naja venom (10 µg) significantly. The median neutralization dose of normal ASVS and released ASVS hemolytic activity of Naja naja venom was found to be 12.5 µg and 12.05 µg respectively (Fig. 4B, 4C). The neutralization capacity of hemolytic activity for released ASVS did not show any significant alteration as compared with normal ASVS in a similar 25 µg dose (Fig. 4D).

Bottom Line: Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required.Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of Calcutta, Kolkata, India; Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India.

ABSTRACT

Background: Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals.

Methodology/principal findings: To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom.

Conclusions/significance: Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid.

Show MeSH
Related in: MedlinePlus