Role of Lipid Peroxidation in Metalloporphyrin-Mediated Phototoxic Reactions in Neonatal Rats

Abstract

ABSTRACT. Our group previously demonstrated dosedependent 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 pW/cm2/nm) for 30 min at 37°C. In the in vivo model, neonatal rat pups were given injections of 40 pmol 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. (Pediatr Res 33: 87-91, 1993) Abbreviations MP, metalloporphyrin SnPP, tin protoporphyrin ZnPP, zinc protoporphyrin MDA, malondialdehyde CD, conjugated diene PUFA, polyunsaturated fatty acid MP are being considered in the treatment of neonatal jaundice. These agents are competitive inhibitors of heme oxygenase, the rate-limiting enzyme in bilirubin production. They can therefore prevent the formation and accumulation of bilirubin (I). However, some MP are potential photosensitizers and could react with ambient fluorescent lights or sunlight to lead to tissue damage (1-6). This effect has been demonstrated in vitro (6)(7)(8) and in vivo (2, 9, 10) with SnPP. Our group and others have shown dose-dependent mortality of neonatal rats treated with SnPP and exposed to light (9-1 1). These same animals did not die when exposed to ZnPP or zinc mesoporphyrin in the presence Supported by a grant from the American Lung Association of California.8 of light (9) or when exposed to SnPP in the dark (8, 9). Mimura et al. (10) have shown that lipid peroxidation is involved in the phototoxicity of SnPP. Therefore, we attempted to confirm and expand on these findings by examining whether lipid peroxidation plays a role in MP-mediated phototoxicity. To accomplish this, we assessed the tissues of neonatal rats treated with SnPP or ZnPP and exposed to light for evidence of lipid peroxidation. MATERIALS AND METHODSReagents. Metalloporphyrin solutions. Four-mM solutions of SnPP and ZnPP (Porphyrin Products, Inc., Logan, UT) were made by dissolving the MP in 500 pL of 10% (vol/vol) ethanolamine followed by the addition of 7 mL H20. Fifty mg of BSA (Sigma Chemical Co., St. Louis, MO) were added. ...

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