Abstract

Abstract:
Approximately 100 million people are exposed to arsenic (As) worldwide, mainly through drinking water and anthropogenic activities. Monosodium methylarsonate (MSMA) is a potent organoarsenical herbicide used in many Asian countries. Epidemiological studies have linked inorganic As exposure with atherosclerosis; however, organoarsenicals toxicological studies are scarce. Paraoxonase 1 (PON1) enzymes suppress systemic oxidized low-density lipoprotein (ox-LDL) generation, thereby preventing atherosclerosis. We investigated the effects of oral exposure to MSMA 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/kgBW, respectively, for 16 weeks. Serum samples were analyzed for PON1 activities, ox-LDL, and malondialdehyde (MDA) levels. Histomorphometric, hematoxylin and eosin (H&E) and Verhoeff–Van Gieson (VVG), and immunohistochemical (vascular adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule 1 (ICAM-1)) evaluations of the rat aortas were conducted. A high mortality rate led to discontinuation of the 126.4 and 210.7 mg/kgBW treatment groups. Groups treated with 42.1 and 63.2 mg/kgBW MSMA had significantly higher MDA levels (P=0.004,CI: 2.73–0.82) and ox-LDL (P

Key words: atherosclerosis, organic arsenic, monosodium methylarsonate (MSMA), paraoxonase 1 (PON1), lipid peroxidation, adhesion molecules (VCAM-1 and ICAM-1).