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).

METHODS AND 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.

CONCLUSION:

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: Stephanie Schulz, Ronald J Wong, Flora S Kalish, Hui Zhao, Kyu Yun Jang, Hendrik J Vreman, David K Stevenson
• Journal: Pediatric research (Pediatr Res) Vol. 72 Issue 2 Pg. 161-8 (Aug 2012) ISSN: 1530-0447 [Electronic] United States
• PMID: 22580722 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Deuteroporphyrins
• Mesoporphyrins
• Photosensitizing Agents
• chromium mesoporphyrin
• zinc deuteroporphyrin IX 2,4-bis(glycol)
• Heme Oxygenase (Decyclizing)
• Bilirubin

Topics

• Animals
• Animals, Newborn
• Bilirubin (biosynthesis)
• Deuteroporphyrins (administration & dosage, pharmacology)
• Dose-Response Relationship, Drug
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors)
• Hyperbilirubinemia, Neonatal (drug therapy)
• Lethal Dose 50
• Light
• Mesoporphyrins (administration & dosage, toxicity)
• Mice
• Photosensitizing Agents (administration & dosage, toxicity)
• Survival Analysis