ABSTRACT
Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medical amino acid widely used as an anti-inflammatory and a whitening agent. This study examined the effect of tranexamic acid administration in wrinkle formation following skin dryness. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In these NOA mice, deterioration of transepidermal water loss (TEWL), generation of wrinkles, decrease of collagen type I, and increases in mast cell proliferation and tryptase and matrix metalloproteinase (MMP-1) release were observed. However, these symptoms were improved by tranexamic acid treatment. Moreover, the increase in the ß-endorphin level in the blood and the expression of µ-opioid receptor on the surface of fibroblasts increased by tranexamic acid treatment. In addition, when the fibroblasts induced by tranexamic acid treatment were removed, the amelioration effect by tranexamic acid treatment was halved. On the other hand, tranexamic acid treated NOA mice and mast cell removal in tranexamic acid treated NOA mice did not result in changes in the wrinkle amelioration effect. Additionally, the amelioration effect of mast cell deficient NOA mice was half that of tranexamic acid treated NOA mice. These results indicate that tranexamic acid decreased the proliferation of mast cells and increases the proliferation of fibroblasts, subsequently improving wrinkles caused by skin dryness.
Subject(s)
Skin Aging/drug effects , Skin Diseases/drug therapy , Tranexamic Acid/therapeutic use , Adrenocorticotropic Hormone/blood , Aminoquinolines/pharmacology , Animals , Antibodies/pharmacology , Benzamides/pharmacology , Body Weight/drug effects , Cell Proliferation/drug effects , Chloroquine/pharmacology , Corticosterone/blood , Immunoglobulin E/blood , Male , Mast Cells/drug effects , Mice , Receptors, Opioid, mu/metabolism , Skin Diseases/blood , Stem Cell Factor/immunology , Tranexamic Acid/pharmacology , Water Loss, Insensible/drug effects , beta-Endorphin/bloodABSTRACT
BACKGROUND: Tranexamic acid has an inhibitory action on ultraviolet (UV) B-induced melanocyte activation. This study examined the sex differences in the inhibitory action of tranexamic acid on UVB-induced melanocyte activation. METHODS: We irradiated the eye and ear of male and female mice with UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp. We orally administered tranexamic acid (750 mg/kg/day) at 30 min before UVB exposure. RESULTS: Tranexamic acid inhibited the UVB-induced epidermal melanocyte activation, and the effect was more remarkable under UVB eye irradiation than under UVB ear irradiation. Furthermore, the melanocyte activity suppression effect was stronger in female mice than in male mice. Following the administration of tranexamic acid, the female displayed increased blood levels of ß-endorphin and µ-opioid receptor and estradiol receptor ß expression in comparison with the male. Furthermore, the effect of melanocyte activity suppression in the female mice was decreased by the administration of tamoxifen (antagonist of estrogen receptor) or naltrexone (antagonist of µ-opioid receptor). CONCLUSIONS: These results suggest that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and ß-endorphin play an important role in this sex difference.
Subject(s)
Antifibrinolytic Agents/pharmacology , Melanocytes/drug effects , Melanocytes/radiation effects , Skin/drug effects , Skin/radiation effects , Tranexamic Acid/pharmacology , Ultraviolet Rays , Adrenocorticotropic Hormone/blood , Animals , Antifibrinolytic Agents/blood , Dihydroxyphenylalanine/analysis , Ear/radiation effects , Estradiol/blood , Estrogen Receptor beta/metabolism , Eye/radiation effects , Female , Male , Melanocytes/chemistry , Mice , Mice, Inbred DBA , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Monophenol Monooxygenase/metabolism , Naltrexone/pharmacology , Narcotic Antagonists/pharmacology , Receptors, Opioid, mu/metabolism , Selective Estrogen Receptor Modulators/pharmacology , Sex Factors , Skin/metabolism , Tamoxifen/pharmacology , Tranexamic Acid/blood , alpha-MSH/blood , beta-Endorphin/blood , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND: Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) is a medicinal amino acid used in skin whitening care. This study examined the effects of tranexamic acid on the melanocyte activation of the skin induced by an ultraviolet (UV) B eye irradiation. METHODS: The eye or ear was locally exposed to UVB at a dose of 1.0 kJ/m(2) using a 20SE sunlamp after covering the remaining body surface with aluminum foil. RESULTS: UVB eye irradiation induced melanocyte activation of the skin, similar to that observed following UVB ear irradiation, which was suppressed by the administration of tranexamic acid treatment. The plasma α-melanocyte-stimulating hormone (α-MSH) content was increased by UVB irradiation of the eye; however, the increase in α-MSH was suppressed by tranexamic acid treatment. In addition, UVB eye irradiation induced the up-regulation of prohormone convertase (PC) 2 in the pituitary gland. Meanwhile, the increase in PC2 induced by UVB eye irradiation was suppressed by tranexamic acid treatment. CONCLUSIONS: These results clearly indicate that tranexamic acid decreases the expression of PC2, which cleavages from proopiomelanocortin to α-MSH in the pituitary gland, thereby suppressing melanocyte activation.