Flora S Kalish

Publications (2)5.4 Total impact

• Article: Effect of Light Exposure on Metalloporphyrin-Treated Newborn Mice.

  Stephanie Schulz, Ronald J Wong, Flora S Kalish, Hui Zhao, Kyu Yun Jang, Hendrik J Vreman, David K Stevenson
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  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-day-old pups (3.75-30.0 µmol/kg i.p.) and exposure to cool white (F20T12CW) and blue (TL20W/52) fluorescent lights (+L) for 3h, resulted in a dose-dependent mortality (LD50=21.5 and 19.5 µmol/kg, respectively). In contrast to ZnBG, there was no significant difference in survival between CrMP+L and CrMP groups. Following 30 µmol/kg ZnBG+L, we found significant weight loss, decreased liver antioxidant capacities, and increased aspartate aminotransaminase (AST) levels. 6-days 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 thus are potentially useful in treating neonatal hyperbilirubinemia.
  Pediatric Research 05/2012; · 2.70 Impact Factor
• Article: Effects of zinc deuteroporphyrin bis glycol on newborn mice after heme loading.

  Cynthia X He, Claire M Campbell, Hui Zhao, Flora S Kalish, Stephanie Schulz, Hendrik J Vreman, Ronald J Wong, David K Stevenson
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  ABSTRACT: Infants with hemolytic diseases frequently develop hyperbilirubinemia and are treated with phototherapy, which only eliminates bilirubin after its production. A better strategy might be to directly inhibit heme oxygenase (HO), the rate-limiting enzyme in bilirubin production. Metalloporphyrins (Mps) are heme analogs that competitively inhibit HO activity in vitro and in vivo and suppress plasma bilirubin levels in vivo. A promising Mp, zinc deuteroporphyrin bis glycol (ZnBG), is orally absorbed and effectively inhibits HO activity at relatively low doses. We determined the I(50) (the dose needed to inhibit HO activity by 50%) of orally administered ZnBG in vivo and then evaluated ZnBG's effects on in vivo bilirubin production, HO activity, HO protein levels, and HO-1 gene expression in newborn mice after heme loading, a model analogous to a hemolytic infant. The I(50) of ZnBG was found to be 4.0 μmol/kg body weight (BW). At a dose of 15 μmol/kg BW, ZnBG reduced in vivo bilirubin production, inhibited heme-induced liver HO activity and spleen HO activity to and below baseline, respectively, transiently induced liver and spleen HO-1 gene transcription, and induced liver and spleen HO-1 protein levels. We conclude that ZnBG may be an attractive compound for treating severe neonatal hyperbilirubinemia caused by hemolytic disease.
  Pediatric Research 07/2011; 70(5):467-72. · 2.70 Impact Factor