Biphasic Hormetic-like Effect of Lebecetin, a C-type Lectin of Snake Venom, on Formalin-induced Inflammation in Mice
- Authors: Belardo C.1, Jebali J.2, Boccella S.3, Infantino R.4, Fusco A.3, Perrone M.5, Bonsale R.4, Manzo I.4, Iannotta M.4, Scuteri D.6, Ferraraccio F.7, Panarese I.7, Ferrara G.7, Guida F.4, Luongo L.4, Palazzo E.4, Srairi-Abid N.8, Marrakchi N.9, Maione S.4
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Affiliations:
- Department of Experimental Medicine, harmacology Division, University of Campania "L. Vanvitelli"
- Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
- Department of Experimental Medicine, Pharmacology Division, University of Campania "L
- Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria
- Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania"L. Vanvitelli"
- Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis,, University of Tunis El Manar,
- Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis,, University of Tunis El Manar
- Issue: Vol 22, No 8 (2024)
- Pages: 1391-1405
- Section: Neurology
- URL: https://hum-ecol.ru/1570-159X/article/view/644874
- DOI: https://doi.org/10.2174/1570159X22999231207105743
- ID: 644874
Cite item
Full Text
Abstract
Background:Integrins, important extracellular matrix (ECM) receptor proteins, are affected by inflammation and can participate in the maintenance of many painful conditions. Although they are ubiquitous and changeable across all cell types, the roles of these cell adhesion molecules in pathological pain have not been fully explored.
Objective:We evaluated the effects of the subcutaneous injection of lebecetin, a C-type lectin isolated from Macrovipera lebetina snake venom, previously reported to inhibit α5β1 and αv integrin activity, on different components of inflammation induced by the formalin administration in the hind paw of mice.
Methods:The formalin-induced nocifensive behavior, edema, and histopathological changes in the hind paw associated with cytokine, iNOS, and COX2 expression, nociceptive-specific neuron activity, and microglial activation analysis in the spinal cord were evaluated in mice receiving vehicle or lebecetin pretreatment.
Results:Lebecetin inhibited the nocifensive responses in the formalin test, related edema, and cell infiltration in the injected paw in a biphasic, hormetic-like, and dose-dependent way. According to that hormetic trend, a reduction in pro-inflammatory cytokines IL-6, IL-8, and TNF-alpha and upregulation of the anti-inflammatory cytokine IL-10 in the spinal cord were found with the lowest doses of lebecetin. Moreover, COX2 and iNOS expression in serum and spinal cord followed the same biphasic pattern of cytokines. Finally, nociceptive neurons sensitization and activated microglia were normalized in the dorsal horn of the spinal cord by lebecetin.
Conclusion:These findings implicate specific roles of integrins in inflammation and tonic pain, as well as in the related central nervous system sequelae.
Keywords
About the authors
Carmela Belardo
Department of Experimental Medicine, harmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Jed Jebali
Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis, University of Tunis El Manar
Email: info@benthamscience.net
Serena Boccella
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli
Email: info@benthamscience.net
Rosmara Infantino
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Antimo Fusco
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli
Email: info@benthamscience.net
Michela Perrone
Department of Experimental Medicine, Pharmacology Division, University of Campania "L
Email: info@benthamscience.net
Roozbe Bonsale
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Iolanda Manzo
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Monica Iannotta
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Damiana Scuteri
Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria
Author for correspondence.
Email: info@benthamscience.net
Franca Ferraraccio
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania"L. Vanvitelli"
Email: info@benthamscience.net
Iacopo Panarese
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania"L. Vanvitelli"
Email: info@benthamscience.net
Giovanna Ferrara
Pathology Unit, Department of Mental and Physical Health and Preventive Medicine, University of Campania"L. Vanvitelli"
Email: info@benthamscience.net
Francesca Guida
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Livio Luongo
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Enza Palazzo
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Email: info@benthamscience.net
Najet Srairi-Abid
Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis,, University of Tunis El Manar,
Email: info@benthamscience.net
Naziha Marrakchi
Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Institut Pasteur of Tunis,, University of Tunis El Manar
Email: info@benthamscience.net
Sabatino Maione
Department of Experimental Medicine, Pharmacology Division, University of Campania "L. Vanvitelli"
Author for correspondence.
Email: info@benthamscience.net
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