In vitro and in vivo characteristics of a heme oxygenase inhibitor: ZnBG.
The authors evaluated the in vitro and in vivo efficacy and photosensitizing effects of zinc deuteroporphyrin 2,4-bis glycol (ZnBG) as an inhibitor of adult Wistar rat tissue heme oxygenase (HO) activity and bilirubin production. Concentrations of 0.02-0.05 microM ZnBG inhibited the HO activity in postmitochondrial supernatants of liver, spleen, brain, and kidney by at least 50%. Administration of 4 mumole ZnBG/kg body weight to adult rats significantly reduced the total body carbon monoxide (CO) excretion, an index of bilirubin formation, from 1 to 6 hours posttreatment. At 6 hours posttreatment, the HO activity in postmitochondrial supernatants of the liver and spleen, but not of the brain, was significantly lowered. ZnBG also behaved as an in vitro photooxidizer by degrading, in the presence of cool white light, the reduced form of nicotinamide adenine dinucleotide phosphate and histidine to CO and other nonidentified products. ZnBG also enhanced the natural photodegradation of bilirubin. Furthermore, administration of ZnBG to 1-day-old neonatal rats caused mortality within 12 hours in light-exposed animals, with a lethal dose 50 of 23 microM/kg body weight.
Vreman
H J
HJ
Department of Pediatrics, Stanford University School of Medicine, California 94305-5119.
Lee
O K
OK
Stevenson
D K
DK
D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001834:Body Water / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism; D003905:Deuteroporphyrins / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000517:prevention & control; D010787:Photosensitivity Disorders / Q000139:chemically induced; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003905:Deuteroporphyrins; D011524:Protoporphyrins; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); C017803:zinc protoporphyrin; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin