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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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Related in: MedlinePlus

In vivo neutralization of venom induced renal toxicity.(A) Measurement of plasma urea concentration in both venom induced group as well as alginate coated ASVS fed animals. (B) Measurement of plasma creatinine concentration in both venom induced group as well as alginate coated ASVS fed animals. (C) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 10×. (C1) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 40×. (D and D1) Microscopic image of renal tissue of alginate coated ASVS bead fed animals after hematoxylin and eosin staining at 10× and 40× respectively.
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pntd-0003039-g006: In vivo neutralization of venom induced renal toxicity.(A) Measurement of plasma urea concentration in both venom induced group as well as alginate coated ASVS fed animals. (B) Measurement of plasma creatinine concentration in both venom induced group as well as alginate coated ASVS fed animals. (C) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 10×. (C1) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 40×. (D and D1) Microscopic image of renal tissue of alginate coated ASVS bead fed animals after hematoxylin and eosin staining at 10× and 40× respectively.

Mentions: After 6 hours of intramuscular administration of Daboia russelii venom (1 mg/kg) plasma creatinine and urea level significantly elevated in venom injected animals as compared with normal group of rats. Oral delivery of 30 mg alginate coated ASVS beads in every 30 minutes up to 6 hour showed significantly decreased level of plasma urea and creatinine by 63.31% and 67.55% in treated group of animals as compared with venom injected group of animals (Fig. 6A, 6B).


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 renal toxicity.(A) Measurement of plasma urea concentration in both venom induced group as well as alginate coated ASVS fed animals. (B) Measurement of plasma creatinine concentration in both venom induced group as well as alginate coated ASVS fed animals. (C) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 10×. (C1) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 40×. (D and D1) Microscopic image of renal tissue of alginate coated ASVS bead fed animals after hematoxylin and eosin staining at 10× and 40× respectively.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0003039-g006: In vivo neutralization of venom induced renal toxicity.(A) Measurement of plasma urea concentration in both venom induced group as well as alginate coated ASVS fed animals. (B) Measurement of plasma creatinine concentration in both venom induced group as well as alginate coated ASVS fed animals. (C) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 10×. (C1) Microscopic image of venom induced alteration in renal tissues after hematoxylin and eosin staining at 40×. (D and D1) Microscopic image of renal tissue of alginate coated ASVS bead fed animals after hematoxylin and eosin staining at 10× and 40× respectively.
Mentions: After 6 hours of intramuscular administration of Daboia russelii venom (1 mg/kg) plasma creatinine and urea level significantly elevated in venom injected animals as compared with normal group of rats. Oral delivery of 30 mg alginate coated ASVS beads in every 30 minutes up to 6 hour showed significantly decreased level of plasma urea and creatinine by 63.31% and 67.55% in treated group of animals as compared with venom injected group of animals (Fig. 6A, 6B).

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