Research Article | Volume: 6, Issue: 11, November, 2016

Organic Arsenical Exposure Stimulates Atherosclerosis through Oxidative Stress Increase and Adhesion Molecule Expression

Afeez Adekunle Ishola,  Norlelawati A.Talib,  Naznin Muhammad,  Zunariah Buyong,  Abdul Hadi Mohamed,  Yiyi Myint,  Niza Samsuddin,  Radiah Abdul Ghani,  Norzamzila Abdullah   
Afeez Adekunle Ishola1, Norlelawati A.Talib1, Naznin Muhammad1, Zunariah Buyong1, Abdul Hadi Mohamed1, Yiyi Myint1, Niza Samsuddin2, Radiah Abdul Ghani2, Norzamzila Abdullah1

1Kulliyyah of Medicine, International Islamic University Malaysia, Jalan Indera Mahkota 2, 25200, Kuantan, Pahang, Malaysia.

2Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Jalan Indera Mahkota 2, 25200, Kuantan, Pahang, Malaysia.

Open Access   

Published:  Nov 29, 2016

DOI: 10.7324/JAPS.2016.601107
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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.


Keyword:     Atherosclerosis Organic arsenic Monosodium methylarsonate (MSMA) Paraoxonase 1 (PON1) Lipid peroxidation adhesion molecules (VCAM-1 and ICAM-1).

Citation:

Ishola AA, Talib NA, Muhammad N, Buyong Z, Mohamed AH, Myint Y, Samsuddin N, Ghani RA, Abdullah N. Organic Arsenical Exposure Stimulates Atherosclerosis Through Oxidative Stress Increase and Adhesion Molecule Expression. J App Pharm Sci, 2016; 6 (11): 040-051.

Copyright:The Author(s). This is an open access article distributed under the Creative Commons Attribution Non-Commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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