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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Main Authors:	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
Format:	Article
Language:	English
Published:	Malaysian Society of Pathologists 2014
Subjects:	RB Pathology
Online Access:	http://irep.iium.edu.my/40185/ http://irep.iium.edu.my/40185/1/IC_Palm_Nor_Zamzila_Abdullah_2014_%28selected_page%29.pdf

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spelling	iium-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 PeerReviewed 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
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RB Pathology
spellingShingle	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
description	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
format	Article
author	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/ http://irep.iium.edu.my/40185/1/IC_Palm_Nor_Zamzila_Abdullah_2014_%28selected_page%29.pdf
first_indexed	2023-09-18T20:57:38Z
last_indexed	2023-09-18T20:57:38Z
_version_	1777410410657349632

Paraoxonase-1 (PON1): bridging the organophosphate exposure to atherosclerosis

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