Partial protection of photodynamic-induced skin reactions in mice by N-acetylcysteine: a preclinical study.
The major side effect of photodynamic therapy (PDT) using Photofrin is enhanced skin sensitivity for sunlight, which persists for 3-8 weeks after injection. Formation of singlet oxygen and radicals is believed to be involved in the basic mechanism of inducing skin damage. Reducing this side effect would make PDT more widely acceptable, particularly for palliative use. Hairless dorsal skin patches of mice, injected with 10 mg kg-1 photofrin intraperitoneally (i.p.) 24 h before illumination, were used to evaluate the effect of increasing light doses. The light was obtained from a halogen lamp and transmitted via a fiber optic to illuminate a field of 2.5 cm2. After establishing a dose-response relationship for single or fractionated light dose illumination of the skin, drugs known to scavenge radicals, quench singlet oxygen or interfere with histamine release were tested for their protective effect. N-acetyl-cysteine (NAC), a radical scavenger, administered i.p. (1000 and 2000 mg kg-1) 1 h before illumination produced a significant decrease in skin damage at light doses > 50 J cm-2 (protection factor of 1.3-1.8). When NAC was administered in a dose of 500 mg kg-1, no protection was observed. Fractionated illumination experiments in combination with multiple injections of NAC (1000 mg kg-1) also failed to show any protection. The addition of Ranitidine, a histamine blocking agent (25-100 mg kg-1), given prior to illumination, resulted in a limited protection at higher light doses. From this study we conclude that NAC could be of value in amelioration of the photosensitivity in patients treated with PDT.
Baas
P
P
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
Oppelaar
H
H
van der Valk
M A
MA
van Zandwijk
N
N
Stewart
F A
FA
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy / Q000009:adverse effects*; D010787:Photosensitivity Disorders / Q000209:etiology / Q000517:prevention & control*; D011899:Ranitidine / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000473:pathology
D011899:Ranitidine; D000111:Acetylcysteine