Modulation of microvascular function following low-dose exposure to the organophosphorous compound malathion in human skin in vivo.
This study investigates whether malathion, a widely used organophosphate insecticide, has its effects on cutaneous vasculature in healthy human volunteers through its anticholinergic activity or through the modulation of other, noncholinergic pathways. Acute, low-dose exposure to malathion (10 mg/ml for 5 h under occlusive dressing) caused a significant increase in cutaneous blood flux, monitored by using laser-Doppler flowmetry and imaging. It had little effect on tissue levels of ACh, nitric oxide, and histamine assayed in dermal dialysate collected from malathion-exposed and control-treated skin. The duration of the cutaneous vascular response to exogenous ACh (2%) delivered by iontophoresis was significantly enhanced by preexposure to malathion, both <1 h after its removal and 24 h later (P < 0.001). At <1 h, the time to 50% decay of the response was 24 +/- 4 and 50 +/- 8 min in control and malathion-treated skin, respectively. Malathion also enhanced the size and duration of the axon reflex-mediated vasoresponse to ACh. The increase in blood flux to malathion and the endothelium-mediated response to exogenous ACh, both in the presence and absence of malathion, were attenuated by pretreatment of the skin with atropine and local anesthesia (P < 0.01). We conclude that short-term exposure to a single low dose of malathion causes prolonged modulation of the physiological function of the cutaneous vasculature and that this is, in part, through its action on acetylcholinesterase at both neuronal and nonneuronal sites.
Boutsiouki
Paraskevi
P
Infection Inflammation and Repair, School of Medicine, Mail Point 825, Southampton General Hospital, Southampton SO16 6YD, UK.
Clough
Geraldine F
GF
D000109:Acetylcholine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000494:pharmacology; D005260:Female; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008294:Malathion / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects* / Q000503:physiopathology
D002800:Cholinesterase Inhibitors; D004785:Environmental Pollutants; D009943:Organophosphorus Compounds; D000109:Acetylcholine; D008294:Malathion