Limits...
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.

Show MeSH

Related in: MedlinePlus

In vivo neutralization of venom induced hemotoxicity.(A1) RBC morphological alteration after venom induction (A2) RBC morphological alteration in alginate coated ASVS fed animals after venom induction, (B) Venom induced clotting time alterations, (C) Hemolysis assay. (C1) Spectrum of plasma hemoglobin, (C2) Pictorial depiction of plasma of venom injected animal and venom injected perorally alginate coated ASVS fed animal. (C3) Assessment of plasma free hemoglobin concentration measurement by Drabkin's methods. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. # Normal control animals vs Venom control animal, * Venom control animal vs alginate coated ASVS fed animal.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4125299&req=5

pntd-0003039-g005: In vivo neutralization of venom induced hemotoxicity.(A1) RBC morphological alteration after venom induction (A2) RBC morphological alteration in alginate coated ASVS fed animals after venom induction, (B) Venom induced clotting time alterations, (C) Hemolysis assay. (C1) Spectrum of plasma hemoglobin, (C2) Pictorial depiction of plasma of venom injected animal and venom injected perorally alginate coated ASVS fed animal. (C3) Assessment of plasma free hemoglobin concentration measurement by Drabkin's methods. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. # Normal control animals vs Venom control animal, * Venom control animal vs alginate coated ASVS fed animal.

Mentions: Intramuscular administration of Daboia russelii venom (1 mg/kg) significantly alter erythrocyte morphology after 120 minutes as seen in light microscopy. Normal discocytic cells have been altered to different morphological shapes like spherocytes, echinocytes, stomatocytes, etc., thereby decreasing the population of discocytes. Oral ASVS beads treatment found to prevent this morphological alterations (Fig. 5A, 5B) in treated group of animals.


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)

In vivo neutralization of venom induced hemotoxicity.(A1) RBC morphological alteration after venom induction (A2) RBC morphological alteration in alginate coated ASVS fed animals after venom induction, (B) Venom induced clotting time alterations, (C) Hemolysis assay. (C1) Spectrum of plasma hemoglobin, (C2) Pictorial depiction of plasma of venom injected animal and venom injected perorally alginate coated ASVS fed animal. (C3) Assessment of plasma free hemoglobin concentration measurement by Drabkin's methods. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. # Normal control animals vs Venom control animal, * Venom control animal vs alginate coated ASVS fed animal.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0003039-g005: In vivo neutralization of venom induced hemotoxicity.(A1) RBC morphological alteration after venom induction (A2) RBC morphological alteration in alginate coated ASVS fed animals after venom induction, (B) Venom induced clotting time alterations, (C) Hemolysis assay. (C1) Spectrum of plasma hemoglobin, (C2) Pictorial depiction of plasma of venom injected animal and venom injected perorally alginate coated ASVS fed animal. (C3) Assessment of plasma free hemoglobin concentration measurement by Drabkin's methods. Result showed as mean ±SEM, n = 6. *p<0.05 was considered significant. # Normal control animals vs Venom control animal, * Venom control animal vs alginate coated ASVS fed animal.
Mentions: Intramuscular administration of Daboia russelii venom (1 mg/kg) significantly alter erythrocyte morphology after 120 minutes as seen in light microscopy. Normal discocytic cells have been altered to different morphological shapes like spherocytes, echinocytes, stomatocytes, etc., thereby decreasing the population of discocytes. Oral ASVS beads treatment found to prevent this morphological alterations (Fig. 5A, 5B) in treated group of animals.

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