Role of lipid peroxidation in metalloporphyrin-mediated phototoxic reactions in neonatal rats.
Our group previously demonstrated dose-dependent mortality in neonatal rats treated with tin protoporphyrin and light. We hypothesize that lipid peroxidation may be responsible for the toxic effects of photosensitizing metalloporphyrins. Neonatal rat blood samples with or without metalloporphyrins (40 mM) were exposed to cool white light (20 microW/cm2/nm) for 30 min at 37 degrees C. In the in vivo model, neonatal rat pups were given injections of 40 mumol of either tin protoporphyrin (4 mM), zinc protoporphyrin/kg body weight, or saline and placed over cool white light. The control animals were similarly treated but kept in the dark. After 3 h, the animals were killed, and their tissues were analyzed for malondialdehyde, conjugated dienes, and disappearance of polyunsaturated fatty acids as indices of lipid peroxidation. In all cases, the known photosensitizer tin protoporphyrin was associated with increased conjugated dienes in the liver and disappearance of polyunsaturated fatty acids and increased malondialdehyde in the liver and brain when animals were exposed to light. Zinc protoporphyrin was not associated with increased lipid peroxidation in the light except in the case of blood in vitro where malondialdehyde levels increased. We conclude that lipid peroxidation plays a role in metalloporphyrin-mediated phototoxicity in neonatal rat tissues.
Dennery
P A
PA
Department of Pediatrics, Stanford University, CA 94304.
Vreman
H J
HJ
Rodgers
P A
PA
Stevenson
D K
DK
D000818:Animals; D000831:Animals, Newborn; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D066298:In Vitro Techniques; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008665:Metalloporphyrins / Q000633:toxicity*; D011524:Protoporphyrins / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D008665:Metalloporphyrins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; C032628:tin protoporphyrin IX