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Organic arsenical exposures stimulates atheroscleorosis through oxidative stress increase and adhesion molecule expression

Ishola, Afeez Adenkule and A Talib, Noorlelawati and Muhammad, Naznin and Buyong, Zunariah and Mohamed, Abdul Hadi and Myint, Yi Yi and Samsuddin, Niza and Abdul Ghani, Radiah and Abdullah, Norzamzila (2016) Organic arsenical exposures stimulates atheroscleorosis through oxidative stress increase and adhesion molecule expression. Journal of Applied Pharmaceutical Science, 6 (11). 040-051. ISSN 2231-3354

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Abstract

Approximately 100 million people are exposed to arsenic worldwide, majorly through drinking water and anthropogenic activities. Monosodium methylarsonate (MSMA) is a potent organoarsenical content of herbicides used in many Asian countries. Epidemiological studies have linked inorganic arsenic exposure with atherosclerosis, whereas organoarsenicals toxicological studies are scanty. Paraoxonase 1 (PON1) enzyme suppresses systemic Ox-LDL generation, thereby preventing atherosclerosis. We investigated effects of MSMA oral exposure on PON1, lipid peroxidation and atherosclerosis development. Five groups (n=11) of Sprague- Dawley rats received daily intubation of MSMA at 0 (control), 42.1, 63.2, 126.4 and 210.7 mg/kg BW respectively for 16 weeks. Serum samples were analysed for PON1 activities, Ox-LDL and MDA levels. Histomorphometric evaluation (H&E and VVG) and immunohistochemistry (VCAM-1 and ICAM-1) were done on aorta. High mortality rate led to discontinuation of 126.4 and 210.7 mg/kg BW treatment groups. Groups treated with 42.1 and 63.2 mg/kg B.W. MSMA had a significantly higher MDA (p=0.004,CI: 2.73-0.82) and Ox-LDL (p<0.0001,CI: 2425.07-955.45) levels but lower PON1:Ox-LDLratio (p<0.0001,CI: 0.49-1.07) compared to control. Microscopically, treatment groups showed early atherosclerotic intima thickening and positive VCAM-1 and ICAM-1 expressions. In conclusion, chronic MSMA exposure reduced PON1 ability to hydrolyse Ox-LDL and also induced inflammation by elevating oxidative stress that supports early atherosclerosis development.

Item Type: Article (Journal)
Additional Information: 4667/53867
Uncontrolled Keywords: Atherosclerosis, Organic arsenic, Monosodium methylarsonate (MSMA), paraoxonase 1 (PON1), lipid peroxidation, adhesion, molecules (VCAM-1 and ICAM-1)
Subjects: R Medicine > RB Pathology
R Medicine > RM Therapeutics. Pharmacology > RM283 Endocrinotheraphy
Kulliyyahs/Centres/Divisions/Institutes: Kulliyyah of Allied Health Sciences > Department of Biomedical Science (Effective:1st July 2011)
Kulliyyah of Medicine > Department of Basic Medical
Depositing User: Dr Radiah Abdul Ghani
Date Deposited: 05 Jan 2017 07:49
Last Modified: 30 May 2017 04:27
URI: http://irep.iium.edu.my/id/eprint/53867

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