title: Effect of light exposure on metalloporphyrin-treated newborn mice.
abstract: BACKGROUND
  Neonatal hyperbilirubinemia arises from increased bilirubin production and decreased bilirubin elimination. Although phototherapy safely and effectively reduces bilirubin levels, recent evidence shows that it has adverse effects. Therefore, alternative treatments are warranted. Metalloporphyrins, competitive inhibitors of heme oxygenase (HO), the rate-limiting enzyme in bilirubin production, effectively reduce bilirubin formation; however, many are photoreactive. Here, we investigated possible photosensitizing effects of chromium mesoporphyrin (CrMP) and zinc deuteroporphyrin bis-glycol (ZnBG).
  
  
  RESULTS
  Administration of CrMP or ZnBG to 3-d-old mouse pups (3.75-30.0 μmol/kg intraperitoneally) and exposure to cool white (F20T12CW) and blue (TL20W/52) fluorescent lights (+L) for 3 h, resulted in a dose-dependent mortality (50% lethal dose (LD50) = 21.5 and 19.5 μmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between the CrMP+L and CrMP groups. Following 30 μmol/kg ZnBG+L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase levels. At 6-d post-light exposure, ZnBG+L-treated pups showed gross and histologic skin changes at doses >7.5 μmol/kg. No lethality was observed following treatment with 30 μmol ZnBG/kg plus exposure to blue light-emitting diodes. Phototoxicity of ZnBG was dependent on light source, emission spectrum, and irradiance.
  
  
  CONCLUSIONS
  Low doses of ZnBG (<3.75 μmol/kg) retained maximal HO inhibitory potency without photosensitizing effects, and therefore are potentially useful in treating neonatal hyperbilirubinemia.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, California, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schulz
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wong
authors.forename: Flora S
authors.initials: FS
authors.lastname: Kalish
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Vreman
authors.forename: David K
authors.initials: DK
authors.lastname: Stevenson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000096:biosynthesis; D003905:Deuteroporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D051556:Hyperbilirubinemia, Neonatal / Q000188:drug therapy*; D007928:Lethal Dose 50; D008027:Light; D008652:Mesoporphyrins / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000633:toxicity*; D016019:Survival Analysis
chemical_list: D003905:Deuteroporphyrins; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C427471:chromium mesoporphyrin; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin