Dual Effects of Alpha-Hydroxy Acids on the Skin

Abstract

AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling agents as well as to ameliorate the appearance of keratoses and acne in dermatology. However, caution should be exercised in relation to certain adverse reactions among patients using products with AHAs, including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo damage of the skin remains unclear, compelling us to ask the question, is AHA a friend or a foe of the skin? The aim of this manuscript is to review the various biological effects and mechanisms of AHAs on human keratinocytes and in an animal model. We conclude that whether AHA is a friend or foe of human skin depends on its concentration. These mechanisms of AHAs are currently well understood, aiding the development of novel approaches for the prevention of UV-induced skin damage.

Keywords: UVB; alpha-hydroxy acids; apoptosis; glycolic acid; keratinocyte.

Figure 1

The structures of AHAs commonly used in dermatology including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid. AHAs are weak organic acids with one or more hydroxyl group attached to the alpha carbon, indicating α. Malic acid and citric acid contain a hydroxyl group in the α-position to one carboxyl group and in the β-position to the other carboxyl group. Tartaric acid is a dicarboxylic acid with two hydroxyl groups at the alpha position of the acid. Malic acid and citric acid are also prominent representatives in alpha hydroxyl acids and beta hydroxyl acids.

Figure 2

Molecular pathways involved in the effects of citric acid and malic acid on HaCaT cells. Citric acid inhibits the proliferation of HaCaT cells via the induction of cell-cycle arrest and apoptosis. Summarizing our previous studies evaluating the effects of treatment with citric acid or malic acid, HaCaT cells exhibit the apoptotic features of apoptotic bodies, DNA damage, and an increase of sub-G1 cells, resulting from activation of caspase-8, -9, and -3 and the induction of AIF and endonuclease G (Endo G) release from mitochondria. Citric acid (CA) and malic acid (MA)-induced apoptosis occur through multiple molecular pathways including the involvement of endoplasmic reticulum (ER) stress- and mitochondria-dependent signaling pathways. Red arrows indicate up-regulation; blue arrows indicate down-regulation. ROS: reactive oxygen species.

Figure 3

Glycolic acid (GA) had anti-inflammatory and photoprotective effects against UVB-irradiation in keratinocytes. (Left) UVB-irradiation activated the nuclear factor-kappa B (NF-kB) pathway and promoted the inflammasome complex assembly, which in ROS accumulation and the release of several proinflammatory cytokines (e.g., interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, IL-Iβ, COX-2, and IL-1β; (Right) Pretreatment with GA could activate DNMT-3B activity and induce the hypermethylation of promoters of NLRC4 and ASC genes, which subsequently hinder of the assembly of the inflammasome complex. GA also inhibited the UVB-induced promoter activity of NF-kB in keratinocyte cells.

Figure 4

Review of the various biological effects (phototoxicity or photoprotection) and mechanisms (apoptosis or anti-inflammation) of GA on human keratinocytes (HaCaT or NHEK), and in the mice animal model.