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In vivo and in vitro effects of porphyrins (tin-protoporphyrin [SnPP], cobalt-mesoporphyrin, haemin and protoporphyrin) on neonatal rats were investigated. Under photoirradiation a high mortality rate was recognized in SnPP injected rats. None died from the application of SnPP without photoirradiation. In photoirradiated rats the median lethal dose (LD50) value of SnPP was calculated to be about 7.4 mumol/kg body weight. Haemolysis and malonaldehyde formation of red blood cells were induced by SnPP together with photoirradiation. SnPP may be useful in reducing bilirubin levels in severely jaundiced infants under non-photoirradiated conditions or dim light, but prophylactic administration of SnPP to the majority of infants is not recommended.

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Lipid peroxidation induced by Sn-protoporphyrin (SnPP) plus photoirradiation was investigated in vivo and in vitro using nonjaundiced Gunn rats. Membrane lipids from young adult rat brain were peroxidized by SnPP plus photoirradiation depending on the SnPP concentration and photoirradiance. Similarly, coadministration of SnPP and photoirradiation to suckling rats increased lipid peroxides in the whole blood and was found lethal. The influence of the wavelength distribution of light sources was also examined by using blue-white and green fluorescent lights. The photodynamic effect by green light irradiation whose energy distribution had no overlap with the Soret band of SnPP was about half of that produced by blue-white light with regard to the membrane peroxidation and the lethal effect on neonatal rats. We therefore conclude that the combination of SnPP and photoirradiation is a potentially hazardous treatment of neonatal jaundice.

ABSTRACT. Our study was undertaken to examine the pharmacological and biological effects of tin-protoporphyrin, a competitive inhibitor of heme oxygenase, on 5-or 6-day-old homozygous Cjlj) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j / j neonates were injected subcutaneously with 20 pmol of tin-protoporphyrintkg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j / j rats was strikingly reduced by the administration of 1 to 100 pmol of tin-protoporphyrin/kg; the most effective dose was 5 pmol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed. (Pediatr Res 24: 209-912, 1988)

The protective effect of free radical scavengers against phototoxicity was investigated with tin-protoporphyrin (SnPP)-treated suckling rats. Six kinds of scavengers (L-ascorbic acid, reduced glutathione, α-tocopherol, retinol, uric acid and cystine) were intraperitoneally injected to rats treated with SnPP plus photoirradiation. Among them, L-ascorbic acid was found to be most effective in protecting SnPP-treated rats against phototoxicity. The survival period was markedly prolonged, and the frequency of abnormal behaviors was reduced with the treatment. Lipid peroxidation in vitro with the brain membrane fraction was also suppressed. The other five substances gave only a little antioxidant effect both in vivo and in vitro. The present study shows that L-ascorbic acid may be a promising chemical to prevent the phototoxicity of SnPP.

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Tin-protoporphyrin (SnPP) was administered to albino rats and the toxic effects of photoirradiation were evaluated. SnPP-treated rats showed no appreciable alterations in physiologic functions in the dark. SnPP-treated suckling rats showed serious responses to photoirradiation in an age-dependent manner. All of the 7-day-old rats died 2 h after the commencement of photoirradiation. However, 0-day-old, 20-day-old, and adult rats tended to tolerate phototoxicity and they survived for 5 h or more under photoirradiation. Suckling rats treated with SnPP plus photoirradiation showed neurological signs such as sudden tumbling with squeaking, while 20-day-old and adult rats died without any symptom. A decrease in the blood pressure and an increase in the heart rate were observed in SnPP-injected, photoirradiated rats. Twenty-day-old rats which had received both SnPP and photoirradiation at postnatal day 5 showed scale formation, sparse hair, turbid cornea, growth retardation of the brain and partial loss of cerebellar granule cells. These results indicate that cautious managements are required for the therapeutic use of photoirradiation for SnPP-injected human babies.