Indomethacin, a Non-steroidal Anti-inflammatory Drug, Induces Skin Dryness via PPARγ in Mice

• Published in: Biological & pharmaceutical bulletin Vol. 45; no. 1; pp. 77 - 85
• Main Authors: Maruyama, Kiyoko, Goto, Kenji, Hiramoto, Keiichi, Tanaka, Shota, Ooi, Kazuya
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.01.2022; Japan Science and Technology Agency
• Subjects: Blood levels; CD163 antigen; CD23 antigen; Celecoxib; Cell proliferation; Collagen (type I); dry skin; Histamine; Immunoglobulin E; Indomethacin; Inflammation; Interleukin 10; Interstitial collagenase; Jejunum; macrophage; Macrophages; mast cell; Mast cells; Matrix metalloproteinase; Metalloproteinase; Nonsteroidal anti-inflammatory drugs; Oral administration; peroxisome proliferation-activated receptor γ; Peroxisome proliferator-activated receptors; Polarity; Prostaglandin endoperoxide synthase; Pruritus; Skin; Small intestine; mast cell; peroxisome proliferation-activated receptor γ; macrophage; dry skin; indomethacin
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b21-00532

Cyclooxygenase (COX)-1-selective inhibitors have side effects such as itching and dryness of the skin. In this study, the degree of skin dryness and the onset mechanism of this condition were investigated by comparing the effects of three non-steroidal anti-inflammatory drugs (NSAIDs) in mice. Mice were orally administered either indomethacin, loxoprofen sodium, or celecoxib (n = 5 per group) once daily for four consecutive days, and blood samples as well as skin and jejunal tissues were isolated on day 5. In the mice treated with indomethacin, transepidermal water loss was significantly increased, and dry skin was observed. In addition, the expression of matrix metalloproteinase (MMP)-I, mast cells, CD163, CD23, CD21, histamine, and peroxisome proliferation-activated receptor (PPAR)γ in the skin and jejunum was increased, and the blood levels of interleukin-10 and immunoglobulin E were also increased. In contrast, the expression of collagen type I in the skin was decreased. These results show that indomethacin activates PPARγ in the skin and jejunum, changes the polarity of macrophages, increases the secretion of MMP-1 from mast cells, and decomposes collagen type I, leading to dry skin.