MORTALITY OF METALLOPORPHYRIN-TREATED NEONATAL RATS AFTER LIGHT EXPOSURE

Tin protoporphyrin (SnPP) has been used to suppress hyperbilirubinemia in human neonates through inhibition of heme oxygenase. Some of the subjects exhibited mild erythema upon receiving phototherapy. SnPP and three proposed alternatives, tin mesoporphyrin (SnMP), zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP) are potential photosensitizers. We therefore studied the phototoxic effects of these compounds in the neonatal rat model. Fed Wistar rats (24-36 h old) were injected intraperitoneally with up to 40 μmol SnPP/kg body weight, 30 μmol SnMP/kg body weight, 60 μmol ZnPP/kg body weight, or 45 μmol ZnMP/kg body weight. The animals were placed over cool white light (20 μW/cm2/nm) for 12 h. Light exposure resulted in SnPP dose-dependent mortality, and the LD50 was determined to be 11.7 μmol/kg body weight. No deaths were observed in pups treated with up to 20 μmol SnMP/kg; treatment with 30 μmol SnMP/kg resulted in a 40% mortality rate. No fatalities were observed among the light-exposed ZuPP- or ZnMP-treated pups. No deaths were observed among control pups treated with the highest metalloporphyrin doses and kept in the dark; similarly, no mortality was observed in untreated lightexposed control animals. We conclude that (1) SnPP and SnMP are potentially fatal phototoxic substances in the neonatal rat; (2) ZnPP and ZnMP may be safer drugs for neonatal rats receiving light exposure, and (3) further studies are needed to fully assess the photobiological hazards of metalloporphyrin administration to humans.