Modulation of 8-methoxypsoralen-photoinduced cutaneous inflammatory reactions by various chemotherapeutic agents in vivo.
Exposure of albino rabbits to UVA-VIS (320-700 nm) radiation after the topical application of 8-methoxypsoralen (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/cm2) 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 125I-HSA and 51Cr-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 (< or = 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.
Kumar
J R
JR
Department of Medicine, University of Toronto, Canada.
Haberman
H F
HF
Ranadive
N S
NS
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004890:Erythema / Q000209:etiology / Q000517:prevention & control; D007052:Ibuprofen / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008730:Methoxsalen / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D011701:PUVA Therapy; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D002722:Chlorobenzenes
D000098:Acetophenones; D007052:Ibuprofen; D007211:Indoles; D007213:Indomethacin; D009637:Masoprocol; D008730:Methoxsalen; D011796:Quinacrine; C060893:MK-886; D002722:Chlorobenzenes; C006821:4-bromophenacyl bromide