Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis
Introduction: Organophosphate (OP) is hydrolyzed by paraoxonase (PON1), an antioxidant enzyme that prevent atherosclerosis by inhibiting oxidative modification of low density lipoprotein (LDL). Low PON1 activities have been observed among individuals chronically exposed to OP while their decreased a...
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my.iium.irep.401852018-06-11T05:53:12Z http://irep.iium.edu.my/40185/ Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis Abdullah, Nor Zamzila A.Talib, Norlelawati Buyong, Zunariah Ku Zaifah, Norsidah Samsuddin, Niza Mohamed, Abdul Hadi Abdullah, Nasuruddin Mat Zainone, Zamzuria Abdul Razak, Redzuan Nul Hakim RB Pathology Introduction: Organophosphate (OP) is hydrolyzed by paraoxonase (PON1), an antioxidant enzyme that prevent atherosclerosis by inhibiting oxidative modification of low density lipoprotein (LDL). Low PON1 activities have been observed among individuals chronically exposed to OP while their decreased activities were reported in individuals with atherosclerosis related disease. However, a connection between chronic OP exposure, PON1 and the development of atherosclerosis has not yet been reported. The aim of this study was to investigate the effects of chronic OP exposure on the development of atherosclerosis in rat model. Materials & Methods: Twenty male Sprague-Dawley rats were divided into 3 groups; Group 1 did not receive any injection, both Group 2 and Group 3 received subcutaneous injection of vehicle and injection of 18.0 mg/kg of chlorpyrifos (CPF) respectively every other day for 180 days. Blood were analyzed for paraoxonase enzyme activities and ox-LDL. Aorta were harvested and stained for light and electron microscopic examination. Results: The paraoxonase activities, oxidized LDL and PON1: ox-LDL ratio were found to be significantly lower in OP exposed rats. The OP exposed rats also showed positive early atherosclerosis changes microscopically with VCAM-1 expression. The electron microscopic (EM) showed evidence of vascular damage with disruptions of the intimal layer of aorta, irregularly oriented and morphologically changed endothelial cells and numerous endothelial gaps with areas of deendothelialization. Discussion: This study highlighted that chronic OP exposure leads to the development of atherosclerosis which is confirmed microscopically and further affirmed by positive VCAM-1 expression. The basis for the above observation could be explain by low PON1 activities and low PON1:ox-LDL ratio. In conclusion, chronic intermittent low dose of OP chlorpyrifos induced the development of early atherosclerosis which could be explained by inability of the PON1 to hydrolyze oxidized-LDL. Keywords: paraoxonase, atherosclerosis, chlorpyrifos, organophsphate, oxidized-low density lipoprotein Malaysian Society of Pathologists 2014-08-01 Article REM application/pdf en http://irep.iium.edu.my/40185/1/IC_Palm_Nor_Zamzila_Abdullah_2014_%28selected_page%29.pdf Abdullah, Nor Zamzila and A.Talib, Norlelawati and Buyong, Zunariah and Ku Zaifah, Norsidah and Samsuddin, Niza and Mohamed, Abdul Hadi and Abdullah, Nasuruddin and Mat Zainone, Zamzuria and Abdul Razak, Redzuan Nul Hakim (2014) Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis. The Malaysian Journal of Pathology, 36. pp. 76-77. ISSN 0126-8635 |
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RB Pathology Abdullah, Nor Zamzila A.Talib, Norlelawati Buyong, Zunariah Ku Zaifah, Norsidah Samsuddin, Niza Mohamed, Abdul Hadi Abdullah, Nasuruddin Mat Zainone, Zamzuria Abdul Razak, Redzuan Nul Hakim Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
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Introduction: Organophosphate (OP) is hydrolyzed by paraoxonase (PON1), an antioxidant enzyme that prevent atherosclerosis by inhibiting oxidative modification of low density lipoprotein (LDL). Low PON1 activities have been observed among individuals chronically exposed to OP while their decreased activities were reported in individuals with atherosclerosis related disease. However, a connection between chronic OP exposure, PON1 and the development of atherosclerosis has not yet been reported. The aim of this study was to investigate the effects of chronic OP exposure on the development of atherosclerosis in rat model. Materials & Methods: Twenty male Sprague-Dawley rats were divided into 3 groups; Group 1 did not receive any injection, both Group 2 and Group 3 received subcutaneous injection of vehicle and injection of 18.0 mg/kg of chlorpyrifos (CPF) respectively every other day for 180 days. Blood were analyzed for paraoxonase enzyme activities and ox-LDL. Aorta were harvested and stained for light and electron microscopic examination. Results: The paraoxonase activities, oxidized LDL and PON1: ox-LDL ratio were found to be significantly lower in OP exposed rats. The OP exposed rats also showed positive early atherosclerosis changes microscopically with VCAM-1 expression. The electron microscopic (EM) showed evidence of vascular damage with disruptions of the intimal layer of aorta, irregularly oriented and morphologically changed endothelial cells and numerous endothelial gaps with areas of deendothelialization. Discussion: This study highlighted that chronic OP exposure leads to the development of atherosclerosis which is confirmed microscopically and further affirmed by positive VCAM-1 expression. The basis for the above observation could be explain by low PON1 activities and low PON1:ox-LDL ratio. In conclusion, chronic intermittent low dose of OP chlorpyrifos induced the development of early atherosclerosis which could be explained by inability of the PON1 to hydrolyze oxidized-LDL.
Keywords: paraoxonase, atherosclerosis, chlorpyrifos, organophsphate, oxidized-low density lipoprotein
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Article |
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Abdullah, Nor Zamzila A.Talib, Norlelawati Buyong, Zunariah Ku Zaifah, Norsidah Samsuddin, Niza Mohamed, Abdul Hadi Abdullah, Nasuruddin Mat Zainone, Zamzuria Abdul Razak, Redzuan Nul Hakim |
author_facet |
Abdullah, Nor Zamzila A.Talib, Norlelawati Buyong, Zunariah Ku Zaifah, Norsidah Samsuddin, Niza Mohamed, Abdul Hadi Abdullah, Nasuruddin Mat Zainone, Zamzuria Abdul Razak, Redzuan Nul Hakim |
author_sort |
Abdullah, Nor Zamzila |
title |
Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
title_short |
Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
title_full |
Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
title_fullStr |
Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
title_full_unstemmed |
Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis |
title_sort |
paraoxonase-1 (pon1): bridging the organophosphate exposure to atherosclerosis |
publisher |
Malaysian Society of Pathologists |
publishDate |
2014 |
url |
http://irep.iium.edu.my/40185/1/IC_Palm_Nor_Zamzila_Abdullah_2014_%28selected_page%29.pdf http://irep.iium.edu.my/40185/ |
_version_ |
1643616508918628352 |
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13.18916 |