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Modulation of 8‐Methoxypsoralen‐Photoinduced Cutaneous Inflammatory Reactions by Various Chemotherapeutic Agents in vivo
Author(s) -
Kumar Janak R.,
Haberman Herbert F.,
Ranadive Narendranath S.
Publication year - 1996
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1996.tb03080.x
Subject(s) - erythema , nordihydroguaiaretic acid , chemistry , in vivo , pharmacology , medicine , cyclooxygenase , dermatology , biochemistry , enzyme , biology , microbiology and biotechnology
— Exposure of albino rabbits to UVA‐VIS (320‐700 nm) radiation after the topical application of 8‐methoxypsor‐alen (8‐MOP) cream is associated with acute cutaneous inflammatory reactions in situ. In the present studies the effects of various agents on 8‐MOP plus light induced cutaneous inflammatory response viz. increase in vascular permeability (iVP), accumulation of polymorphonuclear leukocytes (aPMN) and erythema formation were investigated. The inflammatory reactions were induced by a single exposure of 8‐MOP‐sensitized sites to UVA‐VIS (9.4J/cm 2 ) light. Indomethacin, p‐bromophenacyl bromide (BPAB), MK886 (trade name of Merck Sharpe & Dome), ibuprofen (IB), nordihydroguaiaretic acid (NDGA) or quinacrine were applied topically in cream base at various times prior to 8‐MOP application. The iVP and aPMN were quantitated 24 h postirradiation using 12S I‐HSA and 51 Cr‐labeled PMN respectively, while erythema was graded visually. The rate of iVP, aPMN and erythema was inhibited almost completely by indomethacin (7.5‐10%) when applied twice, 18 h and 3 h prior to 8‐MOP. At lower concentrations of indomethacin (5%) iVP was inhibited whereas aPMN was augmented. The BPAB (0.25%) inhibited more than 90% of 8‐MOP‐photoinduced iVP and aPMN while there was partial reduction in erythema. The MK886 (0.1%) cream inhibited about 50% of iVP and aPMN but erythema persisted. The agents that are somewhat nonspecific such as IB, quinacrine and NDGA inhibited 8‐MOP‐photoinduced inflammation only marginally at the concentrations tested. The fact that iVP, aPMN and erythema can be dissociated suggests that there are independent variables in 8‐MOP‐photoinduced reactions, which involve multifactorial mechanisms probably controlled by different cell‐signalling pathways and mediators.