Tranexamic Acid Ameliorates Nonmelanoma Skin Cancer Induced by Long‐term Ultraviolet A Irradiation

Abstract

To date, there have been no treatments developed to ameliorate nonmelanoma skin cancer induced by long‐term exposure to ultraviolet A (UVA) irradiation. In this study, we examined the effects of tranexamic acid (trans‐4‐aminomethyl cyclohexanecarboxylic acid) on long‐term UVA‐induced skin cancer. We exposed the dorsal skin of male hairless mice to UVA at a dose of 110 kJ m−2 using an FL20SBLB‐A lamp three times weekly for 15 weeks after application of 7,12‐dimethylbenz [a] anthracene (DMBA). During the experimental period, the mice were administered tranexamic acid (750 mg kg−1 day−1) three times weekly. We found that cancer development was ameliorated by administration of tranexamic acid. Furthermore, tranexamic acid treatment was observed to suppress increases in the plasma levels of matrix metalloproteinase‐9 and interleukin (IL)‐6, and skin expression of plasmin, CC chemokine 2, macrophages, signal transducer and activator of transcription (STAT)3, cyclin D and vascular endothelial growth factor (VEGF)‐A that occurred in mice subjected to long‐term UVA irradiation. These results indicated that the nonmelanoma skin cancer induced by DMBA+UVA long‐term irradiation is ameliorated by tranexamic acid through regulation of the plasmin/macrophage/IL‐6/STAT3/cyclin D signal transmission pathway. In addition, this ameliorative effect against skin cancer may be mediated via inhibition of the IL‐6‐induced expression of VEGF‐A.

Long-term UVA exposure to the eye compromises memory and learning ability in mice via corticotropin-releasing hormone type 2 receptor

“…The role of long-term UVA irradiation is well-known in causing chronic photooxidative stress and inflammation (18). CRH and urocortin 2 are the important mediators of the effects of physiological stress (19).…”

Decreased Memory and Learning Ability Mediated by Bmal1/M1 Macrophages/Angptl2/Inflammatory Cytokine Pathway in Mice Exposed to Long-Term Blue Light Irradiation

“…The homogenates were centrifuged, and the supernatants were obtained. Western blotting was performed as previously described [24]. The membranes were incubated at room temperature for 1 h with primary antibodies against brain and muscle arnt-like 1 (Bmal1) (1:1000; Cell Signaling Technology, Danvers, MA, USA), Cryptochrome 1 (Cry1) (1:1000; Proteintech Group, Rosemont, IL, USA), Cry2 (1:1000; Proteintech Group, Rosemont, IL, USA), ionized calcium-binding adapter protein 1 (Iba1; marker of microglia (1:1000; Wako, Osaka, Japan), CC-Chemokine receptor 7 (CCR7) (1:1000; Abcam; Cambridge, MA, USA), and β-actin (1:5000; Sigma-Aldrich, St. Louis, MO, USA) as loading controls.…”