DNA Methyltransferases in Malar Melasma and Their Modification by Sunscreen in Combination with 4% Niacinamide, 0.05% Retinoic Acid, or Placebo

Abstract

Background. Malar melasma has a chronic and recurrent character that may be related to epigenetic changes. Objective. To recognize the expression and DNA methylation of DNA methyltransferases (DNMTs) in malar melasma and perilesional skin, as well as the changes in DNMTs after their treatment with sunscreen in combination with 4% niacinamide, 0.05% retinoic acid, or placebo. Methods. Thirty female patients were clinically evaluated for the expression of DNMT1 and DNMT3b using real-time PCR and immunofluorescence. These initial results were compared to results after eight weeks of treatment with sunscreen in combination with niacinamide, retinoic acid, or placebo. Results. The relative expression of DNMT1 was significantly elevated in melasma compared with unaffected skin in all subjects, indicating DNA hypermethylation. After treatment, it was decreased in all groups: niacinamide (7 versus 1; p<0.01), retinoic acid (7 versus 2; p<0.05), and placebo (7 versus 3; p<0.05), which correlates with clinical improvement. DNMT3b was not overexpressed in lesional skin but reduced in all groups. Conclusions. We found DNA hypermethylation in melasma lesions. Environmental factors such as solar radiation may induce cellular changes that trigger hyperpigmentation through the activation of pathways regulated by epigenetic modifications. However, limiting or decreasing DNA methylation through sunscreen, niacinamide, and retinoic acid treatments that provide photoprotection and genetic transcription can counteract this.

Genome-Protecting Compounds as Potential Geroprotectors

“…[ [765][766][767][768][769][770][771][772][773][774] Vitamin B 3 NAD + precursor, it provides sirtuin activity. HDAC III inhibitor, determines heterochromatin remodeling.…”

Niacinamide for the treatment of melasma: an integrative review of randomized clinical trials

“…The studies were developed in different countries, such as Brazil, 25% (Santos-Caetano et al, 2019), Mexico, 50% (Navarrete-Solís et al, 2011;Campuzano-García et al, 2019) e Korea, 25% (Lee et al, 2016) The instrument for analyzing the methodological quality of the studies selected to assess the response to treatment with niacinamide in patients with melasma found that all (100%) used the treatment concomitantly during eight weeks of treatment (Table 1). However, three articles (75%) did not refer to the complete dosage (nº 1, 2, 4), that is, whether niacinamide was applied during the day or night, or in both situations.…”

Melasma: A Condition of Asian Skin

“…Increased expression of these methyltransferases may lead to greater expression of pro-inflammatory and pro-melanogenic genes. In an eight-week randomized double-blind controlled trial of 30 patients, it was found that there are significantly higher levels of DNMT1 on melasma skin as compared to healthy skin [ 15 ]. DNMT1 is implicated in the hypermethylation of DNA.…”

“…DNMT1 is implicated in the hypermethylation of DNA. Environmental factors such as ultraviolet (UV) radiation may also contribute to hyperpigmentation by activating pathways regulated by epigenetic modifications [ 15 ].…”