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Inhibition of key enzymes linked to snake venom induced local tissue damage by kolaviron

  • Azubuike Ikechukwu Okafor EMAIL logo and Elewechi Onyike
Published/Copyright: December 14, 2020
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 32 Issue 6

Abstract

Objectives

Snakebite envenoming is an important public health problem that threatens the lives of healthy individuals especially in many tropical countries like Nigeria. Antivenins, the only efficient approach for snakebite envenoming, are limited in their efficacy in the neutralization of local tissue damage. Snake venom phospholipase A2 (PLA2), protease, hyaluronidase and l-amino acid oxidase (LAAO) are the major hydrolytic enzymes involve in local tissue damage. Therefore, this study evaluates the inhibitory effect of kolaviron (KV) against Naja n. nigricollis (NNN) snake venom hydrolytic enzymes involved in local tissue damage.

Methods

Kolaviron was evaluated for its ability to inhibit the hydrolytic enzyme activities of NNN venom phospholipase A2 (PLA2), protease, hyaluronidase and l-amino acid oxidase (LAAO). Present study also deals with the neutralization of NNN venom enzyme(s) induced complications such as myotoxic, edemic, hemolytic and procoagulant effects.

Results

Kolaviron inhibited the PLA2, protease, hyaluronidase and LAAO enzyme activities of NNN venom in a dose-dependent manner. Furthermore, myotoxic, edemic, hemolytic and procoagulant effects induced by NNN venom enzyme were neutralized significantly (p<0.05) when different doses of KV were pre-incubated with venom before assays.

Conclusions

These findings clearly present kolaviron as a potent inhibitor against NNN venom hydrolytic enzymes involved in local tissue damage and may act by either forming an inhibitor-enzyme complex that restricts the substrate availability to the enzyme or direct binding to the enzyme active site that affects the enzyme activity thereby mitigating venom-induced toxicity.

Keywords: antivenin; hydrolytic enzymes; inhibition; kolaviron; local tissue damage; Naja nigricollis nigricollis venom
Corresponding author: Azubuike Ikechukwu Okafor, Department of Medical Biochemistry, Cross River University of Technology, Calabar, Nigeria, Phone: +2348035723454, E-mail:

Acknowledgments

The authors wish to thank Professor MS Abubakar and Professor HM Inuwa, for their scientific/technical contributions and also Dr. Peter Ofili, for providing Naja nigricollis nigricollis venom.

  1. Research funding: None declared.

  2. Author contributions: All authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Ethical approval for this study (CRUTECH/FBMS/IREC/2019-A0562) was obtained from Institution Research Ethical Committee of Cross River University of Technology (CRUTECH), Calabar, Nigeria. Venous blood from healthy, non-smoking human volunteers was drawn with verbal informed consent and other protocols were performed in accordance to the Institutional Research Ethical Committee guidelines and with the principle laid down in the Declaration of Helsinki (1964), as revised in 2013.

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Received: 2020-06-05
Accepted: 2020-10-30
Published Online: 2020-12-14

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jbcpp-2020-0176
Keywords for this article
antivenin; hydrolytic enzymes; inhibition; kolaviron; local tissue damage; Naja nigricollis nigricollis venom

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Historical account of endocrinal disorders in Unani medicine
  4. Original Articles
  5. Impact of sleep disturbances and autonomic dysfunction on the quality of life of patients with fibromyalgia
  6. Effects of date seeds administration on anxiety and depressive symptoms in streptozotocin-induced diabetic rats: biochemical and behavioral evidences
  7. Piroxicam reduces acute and chronic pain response in type 1 diabetic rats
  8. Protective effect of Elateriospermum tapos in maternal obesity-induced deficit cognitive function of the offspring
  9. Pharmacological investigations on efficacy of Phlorizin a sodium-glucose co-transporter (SGLT) inhibitor in mouse model of intracerebroventricular streptozotocin induced dementia of AD type
  10. Concurrent administration of acetaminophen and ethanol: impact on mouse liver and testis
  11. Electrical vestibular nerve stimulation as an adjunctive therapy in the management of type 2 diabetes
  12. Effect of roxithromycin on contractile activity of gastrointestinal smooth muscles in colitic rats
  13. Anti-inflammatory and analgesic effects of methanol extract of red cultivar Allium cepa bulbs in rats and mice
  14. Prophylactic effect of aquatic extract of stevia on acetic acid induced-ulcerative colitis in male rats: a possible role of Nrf2 and PPARγ
  15. Molecular docking study of flavonoid compounds for possible matrix metalloproteinase-13 inhibition
  16. Inhibition of key enzymes linked to snake venom induced local tissue damage by kolaviron
  17. Hepatoprotective effects of Quassia amara stem bark against cadmium-induced toxicity in male Wistar rats
  18. Curative effects of the aqueous extract of Tithonia diversifolia (Hemsl.) A. gray (Asteraceae) against ethanol induced-hepatotoxicity in rats
  19. The effect of deer antler from East Kalimantan to increase trabecular bone density and calcium levels in serum on osteoporotic mice
  20. Case Report
  21. A case of statin-induced liver injury with positive rechallenge with a second statin. Is there a class effect?
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