Paraoxonase (PON1) activities and lipid parameters among organophosphate pesticide exposed workers

Abstract

Paraoxonase (PON1) is a high density lipoprotein (HDL)-associated enzyme which is known to hydrolyze organophosphates (OPs) into harmless substances and prevent atherosclerosis by inhibiting oxidative modification of low density lipoprotein (LDL). Reports showed low PON1 activity among OPs-exposed individuals, while low PON1 activity was associated with a high risk of coronary artery disease (CAD). Relationship between OPs exposure and lipid parameters, which are known risk factors of CAD, has not yet been reported in Malaysia. This study aimed at comparing the activities of PON1 and lipid parameters (ox-LDL, TC, TG, LDL-C and HDL-C) between workers who are exposed to OPs and non-exposed comparative groups as well as to study the correlations between PON1 activities and lipid parameters among OPs-exposed group. A total of 103 subjects (53 OPs-exposed and 50 non-exposed) were recruited. Fasting serum samples were analyzed for PON1 activities towards substrates paraoxon, phenylacetate and diazoxon as well as for lipid profiles and oxidized-LDL (ox-LDL). Results showed lower basal paraoxonase activity [156.96 (58.87) vs 177.06 (66.78)], arylesterase activity [90.06 (17.14) vs 96.92 (23.87)] and diazoxonase activity [850.93 (206.75) vs 990.48 (248.73)] among OPs-exposed as compared to non-exposed, but only diazoxonase activity was significantly lower (p<0.05). There was significantly higher ox-LDL [4.89 (3.94) vs 2.83 (1.63)] (p<0.05) among the OPs-exposed group. There were no differences in lipid profiles (p>0.05) between the two groups and no significant correlations between PON1 activities and lipid profiles among OPs-exposed group. The PON1 to ox-LDL ratio which probably reflects the ability of PON1 to hydrolyze ox-LDL were also significantly lower (p<0.05) among OPs-exposed group. Our study suggested that the decreased PON1 activity among OPs-exposed individuals could be a predisposition to development of atherosclerosis and CAD through decreased PON1 ability to hydrolyze ox-LDL but not through lipid profiles. A larger scale study is required to confirm our observation.