Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

Wataru Watanabe,Asami Shibata,Satoko Hongo,Nao Kuroki,Akihiko Hirose,Tomomi Takeshita,Toshi Akashi,Masahiko Kurokawa,Seiko Hashiguchi,Katsuhiko Konno,Hiroki Yoshida

doi:10.1155/2013/151807

Abstract

Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV) infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm) in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6) and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.

Highlights

Methamidophos, an organophosphate insecticide, is a wellknown toxicant, and its usage is restricted during planting of vegetables [1]
No particular toxicological sign or abnormal behavior was observed in offspring mice
No histopathological change was found in lung tissues of mock-infected offspring mice treated with or without methamidophos. These results indicated that perinatal exposure to methamidophos did not affect the growth of respiratory syncytial virus (RSV) but suppressed moderately the expansion of the virus-induced pneumonia in offsprings

Summary

Introduction

Methamidophos, an organophosphate insecticide, is a wellknown toxicant, and its usage is restricted during planting of vegetables [1]. It was reported that the levels of methamidophos in horticultural greenhouse workers continuously exposed to it were similar to those who ingested methamidophos-contaminated food [2]. A representative mechanism of action of methamidophos is inhibition of cholinesterase in the central nervous system, but delayed neuropathy is speculated to be due to no association with acetylcholinesterase [3]. Toxic effects of methamidophos on male reproductive organs were reported [4]. Except for those on the central nervous system, the cumulative effects of exposure to methamidophos, either directly or in utero, on living organism have not been elucidated clearly. To protect mothers and children from environmental contaminants including organophosphate

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Results

Conclusion