Lactoperoxidase catalyzes in vitro activation of acrylonitrile to cyanide.
Acrylonitrile (ACN) is a widely used industrial chemical. Although it is a well reported animal carcinogen, its current designation to humans is "possibly carcinogenic". The present study aimed at investigating the ability of LPO enzyme system to oxidize ACN to cyanide (CN(-)) in vitro. Detection of CN(-) served as a marker for the possible generation of free radical intermediates implicated in ACN induced toxicity in the activation process. Optimum conditions for the oxidation of ACN to CN(-) were characterized with respect to pH, temperature and time of incubation as well as ACN, LPO and H(2)O(2) concentrations in incubation mixtures. Maximum reaction velocity (V(max)) and Michaelis-Menten constant (K(m)) were assessed. Addition of nitrite (NO(2)(-)) salts to the reaction mixtures significantly enhanced the rate of the reaction. Free radical scavengers (quercetin and trolox C), LPO enzyme inhibitor (resorcinol) and competitors for LPO binding (sodium azide and indomethacin) were found to reduce the rate of CN(-) production. Inclusion of the sulfhydryl compounds glutathione (GSH), NAC (N-acetylcysteine), D-penicillamine or L-cysteine enhanced the rate of ACN oxidation. The present results demonstrate the ability of LPO enzyme system to oxidize ACN to CN(-) and provide insight for the elucidation of ACN chronic toxicity.
Nasralla
Sherry N
SN
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Ghoneim
Asser I
AI
Khalifa
Amani E
AE
Gad
Mohamed Z
MZ
Abdel-Naim
Ashraf B
AB
D000181:Acrylonitrile / Q000378:metabolism*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D002384:Catalysis; D002839:Chromans / Q000494:pharmacology; D003486:Cyanides / Q000378:metabolism*; D003627:Data Interpretation, Statistical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology; D012118:Resorcinols / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D013696:Temperature
D002273:Carcinogens; D002839:Chromans; D003486:Cyanides; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D012118:Resorcinols; D013438:Sulfhydryl Compounds; D019810:Sodium Azide; D011794:Quercetin; D006861:Hydrogen Peroxide; D007784:Lactoperoxidase; D000181:Acrylonitrile; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D007213:Indomethacin; C031389:resorcinol