Background & Aims

Burns are an important global health problem. They are caused by several factors, including ultraviolet (UV) radiation [1,2]. Exposure to ultraviolet B (UVB) radiation can result in sunburn and a consequent inflammatory response that contributes to the development of pain, oedema, inflammatory cell infiltration and erythema [3–6]. Pharmacological treatments often lack efficacy, and prolonged use can cause adverse effects that limit their use [3,7–12]. Therefore, the search for new therapeutic alternatives is necessary. Diosmetin, an aglycone of the flavonoid glycoside diosmin, has antinociceptive, antioxidant, anti-inflammatory and anticancer properties [6,13–17]. Therefore, we developed a topical formulation containing diosmetin and evaluated its antinociceptive and anti-inflammatory potential in a UVB radiation-induced sunburn model in mice.

Methods

Male Swiss mice (25-30g) (CEUA: #4884040522/2022) were anaesthetized, and only the right hind paw was exposed a single once to UVB radiation for 20.5 minutes (0.75 J/cm2). The treatments were applied topically (15 mg/paw) once a day for 5 days, with gel formulations (formulation gel based on Pemulen® TR2) containing diosmetin (0.01, 0.1 and 1%) or dexamethasone (0.1%; reference drug) [18,19]. The antinociceptive effects of the formulations were evaluated by the mechanical paw withdrawal threshold and pain affective-motivational behaviour using von Frey filaments. Anti-inflammatory activity was determined by measuring paw thickness with a digital calliper and infiltration of inflammatory cells through histological analysis [6,18–21]. The results were expressed as mean + standard error of the mean (SEM) and analyzed by one- or two-way ANOVA followed by Bonferroni’s post hoc test or median and interquartile range evaluated using the Kruskal–Wallis test, followed by Dunn’s test.

Results

Topical diosmetin (0.1 and 1%) reduced the UVB radiation-induced mechanical allodynia from 2 to 4 days after irradiation, with maximum inhibition (Imax) of 85.2±19.6% to 1% diosmetin on the 2nd day. Topical diosmetin (0.01, 0.1 and 1%) attenuated the pain affective-motivational responses from 1 to 4 days after irradiation, with Imax of 85.7±7.2% to 0.01% diosmetin on day 3. The paw oedema was reduced by topical 1% diosmetin on the 2nd and 4th days after irradiation with inhibition of 87.5±10.2% on the 2nd day. Also, it reduced the number of inflammatory cells in the plantar tissue by 100%. Topical 0.1% dexamethasone reduced mechanical allodynia and the pain affective-motivational behaviour from 2 to 4 days, with Imax of 100% and 76.97±4.07% on the 2nd day after irradiation, respectively. Moreover, reduced the paw oedema from 2 to 4 days after irradiation with Imax of 100% on the 2nd day and the number of inflammatory cells in the plantar tissue by 100% compared to the irradiated group.

Conclusions

Our results indicate that diosmetin may be a promising therapeutic strategy for the treatment of inflammatory pain associated with sunburn, as it alleviated both nociceptive and inflammatory parameters in our study. Relevantly, diosmetin is considered relatively safe because it has not shown toxic adverse effects in previous studies [13,22]. However, more studies are still needed to investigate its adverse effects, with its prolonged use and in combination with other medications.

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Presenting Author

Amanda Favarin da Silva

Poster Authors

Amanda Favarin da Silva

undergraduate

Federal University of Santa Maria

Lead Author

E-mail

Gabriela Becker

Federal University of Santa Maria

Lead Author

E-mail

Evelyne Silva Brum

PhD

Federal University of Santa Maria

Lead Author

E-mail

Maria Fialho

Federal University of Santa Maria, Santa Maria, RS, Brazil

Lead Author

E-mail

Lara Panazzolo Marquezin

Federal University of Santa Maria

Lead Author

E-mail

Patrick Tuzi Serafini

Federal University of Santa Maria

Lead Author

E-mail

Sara Marchesan Oliveira

PhD

Federal University of Santa Maria

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Burn Pain