Topical atorvastatin ameliorates 12-O-tetradecanoylphorbol-13- acetate induced skin inflammation by reducing cutaneous cytokine levels and NF-jB activation

• Published in: Archives of pharmacal research pp. 1238 - 1247
• Main Authors: Nagaraj M. Kulkarni, Milind M. Muley, Mallikarjun S. Jaji, G. Vijaykanth, J. Raghul, Neetin Kumar D. Reddy, Santosh L. Vishwakarma, Navin B. Rajesh, Jeyamurugan Mookkan, Uma Maheswari Krishnan, Shridhar Narayanan
• Format: Journal Article
• Language: English
• Published: 대한약학회 01.06.2015
• Subjects: 약학
• ISSN: 0253-6269; 1976-3786

Atorvastatin is a 3-hydroxy-3-methylglutarylcoenzyme-A reductase inhibitor used in the treatment ofatherosclerosis and dyslipidemia. Studies have evaluatedthe utility of statins in the treatment of skin inflammationbut with varied results. In the present study, we investigatedthe effect of atorvastatin on TNF-a release andkeratinocyte proliferation in vitro and in acute and chronic12-O-tetradecanoylphorbol-13-acetate (TPA) induced skininflammation in vivo. Atorvastatin significantly inhibitedlipopolysacharide induced TNF-a release in THP-1 cellsand keratinocyte proliferation in HaCaT cells. In an acutestudy, topical atorvastatin showed dose dependent reductionin TPA induced skin inflammation with highest efficacyobserved at 500 lg/ear dose. In chronic study, topicalatorvastatin significantly reduced TPA induced ear thickness,ear weight, cutaneous cytokines, MPO activity andimproved histopathological features comparable to that ofdexamethasone. Atorvastatin also inhibited TPA stimulatedNF-jB activation in mouse ear. In conclusion, our resultssuggest that atorvastatin ameliorates TPA induced skininflammation in mice at least in part, due to inhibition ofcytokine release and NF-jB activation and may be beneficialfor the treatment skin inflammation like psoriasis. KCI Citation Count: 15