Modulation of 8-methoxypsoralen-photoinduced cutaneous inflammatory reactions by various chemotherapeutic agents in vivo.

Abstract

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.

• Authors: J R Kumar, H F Haberman, N S Ranadive
• Journal: Photochemistry and photobiology (Photochem Photobiol) Vol. 63 Issue 4 Pg. 535-40 (Apr 1996) ISSN: 0031-8655 [Print] United States
• PMID: 8934766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Indoles
• MK-886
• Masoprocol
• Quinacrine
• 4-bromophenacyl bromide
• Methoxsalen
• Ibuprofen
• Indomethacin

Topics

• Acetophenones (pharmacology)
• Animals
• Capillary Permeability (drug effects)
• Erythema (etiology, prevention & control)
• Ibuprofen (pharmacology)
• Indoles (pharmacology)
• Indomethacin (pharmacology)
• Masoprocol (pharmacology)
• Methoxsalen (pharmacology)
• Neutrophils (drug effects)
• PUVA Therapy
• Quinacrine (pharmacology)
• Rabbits
• Skin (drug effects, radiation effects)