Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 mumol SnPP/kg body weight, 30 mumol SnMP/kg body weight, 60 mumol ZnPP/kg body weight, or 45 mumol ZnMP/kg body weight. The animals were placed over cool white light (20 microW/cm2/nm) for 12 h. Light exposure resulted in SnPP dose-dependent mortality, and the LD50 was determined to be 11.7 mumol/kg body weight. No deaths were observed in pups treated with up to 20 mumol SnMP/kg; treatment with 30 mumol SnMP/kg resulted in a 40% mortality rate. No fatalities were observed among the light-exposed ZnPP- 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 light-exposed 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.
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PMID:Mortality of metalloporphyrin-treated neonatal rats after light exposure. 236 56

In two separate studies, in which two different treatment regimens of Sn-protoporphyrin were used, a total of 69 control and 53 treated infants were studied to determine whether this potent inhibitor of the enzyme, heme oxygenase, could ameliorate the severity of the hyperbilirubinemia which develops in term babies with direct Coombs-positive ABO incompatibility. The results indicate that Sn-protoporphyrin can, in appropriate doses, moderate the postnatal rate of increase of plasma bilirubin levels and diminish the intensity of hyperbilirubinemia in treated babies. In addition, a decreased use of phototherapy in Sn-protoporphyrin-treated infants was observed. No rebound hyperbilirubinemia was detected during the six- to eight-day period after Sn-protoporphyrin administration. The plasma clearance (t1/2) of Sn-protoporphyrin was much faster in newborns than in adults (approximately 1.6 hours v 3.5 hours, respectively). The incidence of clinical side effects in the 53 Sn-protoporphyrin-treated infants was limited to the development of transient erythema during the use of concurrent phototherapy in two babies. In both infants this reaction subsided completely without sequelae. The use of Sn-protoporphyrin or related synthetic heme analogues to diminish the severity of hyperbilirubinemia in newborn infants merits further study because inhibition of the rate-limiting enzyme in the catabolism of heme to bilirubin may prove to be a useful therapeutic approach in the clinical management of neonatal hyperbilirubinemia, especially in settings in which, for social or economic reasons, other treatment modalities are not available.
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PMID:Sn-protoporphyrin use in the management of hyperbilirubinemia in term newborns with direct Coombs-positive ABO incompatibility. 328 Nov 27

Pure synthetic metalloporphyrins have been developed for experimental and clinical use as inhibitors of heme oxygenase, the rate limiting enzyme in the catabolism of heme to bilirubin. Tin (Sn)-protoporphyrin is one such compound, which potently suppresses bilirubin production and thus jaundice in animals and man. We have previously reported that this metalloporphyrin in conjunction with UVA might be useful as a treatment for psoriasis. To assess the photodynamic properties of Sn-protoporphyrin, 31 subjects were investigated with regard to photosensitivity. In all subjects, phototesting using UVB, UVA, and visible light as well as photopatch testing was performed. Our investigations revealed that 16 of the 31 individuals treated with Sn-protoporphyrin developed a mild photosensitivity, mainly erythema of the hands and face, and in some cases a mild conjunctivitis. The duration of this sensitivity, which in no case caused discomfort, was dose-dependent and ranged from several weeks to 1-3 months. After administration of Sn-protoporphyrin, lower thresholds were found for both UVA and visible light, but the sensitivity for UVB was normal and photopatch tests were negative. In summary, the photosensitivity observed during Sn-protoporphyrin administration was of limited duration and magnitude and did not occur in all subjects. Thus, the combination of photoactive synthetic metalloporphyrins and artificial light might prove to be useful as a regimen for the treatment of skin disease.
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PMID:Photodynamic properties of Sn-protoporphyrin: clinical investigations and phototesting in human subjects. 809 46

Solar UVB (290-320 nm) and particularly UVA (320-380 nm) radiations have a capacity to generate reactive chemical species, including free radicals, in cells. These intermediates have been shown to be involved in various biological effects in cultured human skin cells (e.g. cell death) and skin (e.g. erythema). Endogenous glutathione is a critical molecule in protection against the cytotoxic effects of both wavelength ranges. Although there is evidence from cellular studies for the involvement of an oxidative component of UVC/UVB radiations in activation of several genes, the doses used are generally extremely cytotoxic and could cause aberrant signalling. Genes activated by sublethal doses of UVA radiations (e.g. haem oxygenase 1 and the CL100 phosphatase) are clearly redox regulated. The strong induction of haem oxygenase 1 in human fibroblasts has been implicated in an adaptive response to oxidative membrane damage that involves increased synthesis of the iron storage protein, ferritin.
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PMID:Ultraviolet radiation and free radical damage to skin. 866 Apr 2

Neonatal jaundice continues to be a common problem. Kernicterus, although rare, continues to be a very real concern in both full-term and preterm infants. The diagnosis of kernicterus requires not only bilirubin staining in a characteristic pattern in the brain but also neuronal damage. With careful pathologic evaluation, kernicterus should be distinguishable from the brain damage associated with asphyxia and hypoxia. Early hospital discharge is a risk factor for the development of kernicterus. Combining the use of traditional phototherapy from above and a fiberoptic blanket from below has improved the effectiveness of phototherapy. Clinical trials with SnMP as an inhibitor of heme oxygenase appear encouraging; no adverse effects were noted, except for mild, occasional photosensitization manifest by erythema in babies receiving phototherapy. One theoretical toxicity of inhibitors of heme oxygenase involves the recent observation that carbon monoxide (CO) is a neurotransmitter in certain regions of the brain, possibly comparable to nitric oxide (NO), and the consequences of such inhibition are unknown. More research is needed to improve our understanding about the entry of bilirubin into the brain, the predilection of bilirubin for certain brain regions, and the cytotoxicity of bilirubin. In the United States, there is currently no generally accepted method to predict hyperbilirubinemia or kernicterus. Brain stem auditory evoked responses and MRI can both be used effectively to monitor the effects of severe hyperbilirubinemia.
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PMID:Bilirubin metabolism and kernicterus. 926 71