title: Sex differences regarding the amelioration of wrinkles due to skin dryness by the administration of tranexamic acid.
abstract: Tranexamic acid (trans-4-aminomethylcyclohexanecarboxylic acid) exerts an amelioration effect on wrinkle formation due to skin dryness. We examined the sex differences in this effect. We administered tranexamic acid (750mg/kg/day) orally for 20 consecutive days to male and female Naruto Research Institute Otsuka Atrichia (NOA) mice, which naturally develop skin dryness. In the treated female mice, the amelioration effect on the wrinkle score, deterioration of transepidermal water loss (TEWL), capacitance, and decrease in the expression of collagen type I was stronger than in the male treated mice. Furthermore, the level of β-endorphin in the plasma and the expression of β-endorphin, μ-opioid receptor, and macrophages in the dorsal skin increased after the administration of tranexamic acid, and this increase was higher in female mice than in males. In addition, the macrophage production was increased by the administration of tranexamic acid in the ovary but did not change after administration in the testes. A histological examination revealed that these macrophages produce the β-endorphin, clarifying the source of the elevated levels. The amelioration effect in the female treated mice was decreased by the administration of clophosome (a macrophage inhibitor) to a degree that did not markedly differ from the effect observed in the male treated mice. These results suggest that the amelioration effect on wrinkles is stronger in female NOA mice than in males and that β-endorphin produced by macrophages plays an important role in this sex difference.
authors.affiliation: Department of Pharmaceutical Sciences, Suzuka University of Medical Science, 3500-3 Minamitamagakicho, Suzuka, Mie 513-8670, Japan. Electronic address: hiramoto@suzuka-u.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Hiramoto
authors.affiliation: R&D Department, Daiichi Sankyo Healthcare Co., LTD., 3-14-10 Nihonbashi, Chuo-ku, Tokyo 103-8234, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: R&D Department, Daiichi Sankyo Healthcare Co., LTD., 3-14-10 Nihonbashi, Chuo-ku, Tokyo 103-8234, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: R&D Department, Daiichi Sankyo Healthcare Co., LTD., 3-14-10 Nihonbashi, Chuo-ku, Tokyo 103-8234, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006813:Humidity; D007267:Injections; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012727:Sex Characteristics; D012871:Skin Diseases / Q000097:blood / Q000188:drug therapy*; D014148:Tranexamic Acid / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D001615:beta-Endorphin / Q000097:blood
chemical_list: D017450:Receptors, Opioid, mu; D001615:beta-Endorphin; D014148:Tranexamic Acid
keywords: Macrophage; Sex difference; Tranexamic acid; Transepidermal water loss; Wrinkle; β-Endorphin