Effect of organophosphate intoxication on human serum paraoxonase.
Recently, interindividual variations in serum paraoxonase (PON1) activity and the differences in its metabolic activity towards different organophosphates (OPs) caused by the coding region polymorphisms L55M and Q192R have been found to be important risk factors in susceptibility to OP poisoning. In this study, we investigated the effect of PON1 on the outcome of acute OP intoxication and the effect of acute OP intoxication on PON1. Twenty-eight OP-poisoned patients and 66 healthy volunteers were studied. Patients were evaluated for the clinical manifestations of OP intoxication as well as PON1 activity, PON1 mass and PON1 polymorphisms. Butyrylcholine-esterase (BChE) activity was 50% lower (2,276 +/- 738 U/L versus 5,037 +/- 1,553 U/L, P<0.01) while PON1 activity was 30% lower [114.2 +/- 67.4 nmol/mL/min versus 152.9 +/- 78.9 nmol/mL/ min, P<0.05) in patients than in controls. We observed that the PON1 and BChE activities of eight of the original subjects returned to normal levels when they were reinvestigated six months after exposure. The frequency of the PON192Q allele was significantly higher in patients than controls (85.7% versus 59.7%, chi2=6.745, P=0.034). QQ/ MM individuals had the lowest activity towards paraoxon, while RR/LL individuals had the highest activity. Our data indicate that interindividual differences in PON1 activity and the PON1-55 and -192 polymorphisms are important risk factors in susceptibility to acute OP poisoning; therefore, identifying an individual's PON1 alloenzymes may play an important role in the treatment of patients suffering from OP intoxication.
Department of Biochemistry, Ege University Faculty of Medicine, Izmir, Turkey.
E Y
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Sözmen
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Mackness
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Sözmen
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Durrington
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Girgin
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Aslan
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Mackness
D043303:Aryldialkylphosphatase; D002091:Butyrylcholinesterase / Q000097:blood; D004950:Esterases / Q000097:blood* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007306:Insecticides / Q000378:metabolism / Q000506:poisoning*; D007902:Length of Stay; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*; D009943:Organophosphorus Compounds; D011041:Poisoning / Q000201:enzymology* / Q000235:genetics; D011110:Polymorphism, Genetic; D014421:Turkey
D007306:Insecticides; D009943:Organophosphorus Compounds; D004950:Esterases; D002091:Butyrylcholinesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human