Abstract
UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm2). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 µg/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1β cytokines levels by 82 ± 8%, 59 ± 10%, 40 ± 12%, and 85 ± 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 ± 10% and reverted SOD activity by 81 ± 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.
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Abbreviations
- ANOVA:
-
Analysis of variance
- BSA:
-
Serum albumin
- CGRP:
-
Calcitonin gene-related peptide
- Dexa 0.5%:
-
0.5% Dexamethasone
- DMSO:
-
Dimethyl sulfoxide
- EDTA:
-
Ethylenediamine tetraacetic acid
- HCl:
-
Hydrochloric acid
- HTAB:
-
Hexadecyl trimethylammonium bromide
- IL-1β:
-
Interleukin 1β
- i.p:
-
Intraperitoneal
- MIP-2:
-
Protein inflammatory macrophage 2
- MPO:
-
Myeloperoxidase
- Na2CO3 :
-
Sodium carbonate
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NaOH:
-
Sodium hydroxide
- NF-κB:
-
Nuclear factor kappa B
- OD:
-
Optical density
- PMSF:
-
Phenylmethane sulfonyl fluoride
- ROS:
-
Reactive oxygen species
- RTX:
-
Resiniferatoxin
- SEM:
-
Standard error of the mean
- SP:
-
Substance P
- TRP:
-
Potential transient receptor
- TRPV1:
-
Potential transient receptor vanilloid 1
- UI:
-
International units
- UVB:
-
Ultraviolet type B
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Acknowledgements
We thank the professor of the Program in Biological Sciences: Toxicological Biochemistry (Federal University of Santa Maria), Vera Morsch, for loaning equipment and all authors for their contribution. We also acknowledge fellowships from CNPq and CAPES.
Funding
Study was supported by the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul-FAPERGS [Grant #17/2551-0001082-5] (Brazil); by the Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq [Grant #406098/2018-2], and by the Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior—CAPES/PROEX [#23038.005450/2020-19, Grant: #0578/2020]. SMO is recipient of fellowship from CNPq [Grant #304985/2020-1]. CC, ESB, IB and NSP are recipient of fellowship from CAPES/PROEX (process #88882.182152/2018-01; process #88887.185973/2018-00; process #88882.182148/2018-01 and process #88882.182128/2018-01).
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Participated in research design: [CC; SMO]. Conducted experiments: [CC; IB; ESB; NSP; NB; SMO]. Performed data analysis: [CC; SMO].Wrote or contributed to the writing of the manuscript: [CC; SMO]. All the authors reviewed the manuscript.
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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted and ethical approval was obtained from Institutional Committee for Animal Care and Use of the Federal University of Santa Maria (Process number 7999090818/2018).
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Camponogara, C., Brum, E.S., Pegoraro, N.S. et al. Diosmetin, a novel transient receptor potential vanilloid 1 antagonist, alleviates the UVB radiation-induced skin inflammation in mice. Inflammopharmacol 29, 879–895 (2021). https://doi.org/10.1007/s10787-021-00802-1
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DOI: https://doi.org/10.1007/s10787-021-00802-1