Effects of malathion on the vascular function in human skin

Abstract

This work examines the effects of a single low-dose of malathion on the cutaneous vasculature in healthy human skin in vivo. The percutaneous delivery of malathion to the tissue space was established using dermal microdialysis. Scanning laser Doppler imaging was used to assess changes in skin blood flow following exposure to a single low-dose of malathion. The effects of changes in local blood flow on the distribution of malathion within the tissue space were also investigated. In addition the mechanisms by which malathion exerts its effects on the vasculature were investigated both directly by the assay of ACh and nitric oxide in dermal dialysates and indirectly using the response to exogenous ACh as a measure of AChE activity. The role of cutaneous muscarinic receptors in the malathion-induced changes in vascular perfusion was also addressed in this study using dermal iontophoresis to deliver agonists and/or antagonists in the skin and laser Doppler fluximetry to monitor the responses of the vasculature to these agents.

The results from the present study demonstrate that malathion is absorbed through the skin and can have direct vasodilator effects which are mediated in part by the increase in tissue levels of ACh and subsequent stimulation of cutaneous muscarinic receptors. This study also showed that tissue levels of malathion are dependent upon local skin blood flow and thus malathion through its effects on the vasculature can influence its own systemic distribution. In addition the results in this study confirm that the responses to ACh are only in part modulated by nitric oxide and demonstrate that at high concentrations ACh has neurogenic effects manifest as flare and itch.

Together these findings result in a better understanding of the factors that contribute to the systemic distribution of malathion following its topical application to the skin, as well as of the mechanisms by which OP's modulate the physiological responses of the cutaneous vasculature. The latter provides valuable information about the potential toxic effects following acute exposure to low-doses of OP's.

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