The effect of diethyldithiocarbamate on brain uptake of cadmium

Abstract

A previous study in mice has shown that the chelating agent diethyldithiocarbamate (DDC), when used to treat intoxication with cadmium, increased the concentration of the metal in brain. Studies were undertaken to confirm these findings in rats and to determine the mechanism of the observed effect. DDC (10 mg/kg, ip) given to male Sprague-Dawley rats 30 min prior to intracarotid Cd administration resulted in a 10-fold increase in the single pass cerebral extraction of cadmium. Two possible mechanisms were studied to explain this observation. First, DDC via a central adrenergic mechanism may cause a generalized increase in cerebral capillary permeability ( CCP) to a diffusion-limited substance or may reduce cerebral blood flow ( CBF) thereby prolonging cerebral circulatory transit time. Second, DDC ma6 chelate Cd to form a complex more permeable to the blood:brain barrier (BBB). CBF was determined from the ratio of [ 14C]butanol taken up by the brain to the [ 14C]butanol in an arterial blood sample withdrawn at a constant rate following iv injection of the tracer. CCP was determined as E w (extraction fraction of water) by the double-diffusion tracer technique. DDC did not alter either parameter, suggesting that the mechanism of the DDC-Cd interaction may involve the formation of a complex more permeable to the BBB. This conclusion is supported by the finding that the addition of DDC to a CdCl 2 solution increased the octanol-water partition coefficient of Cd (as DDC-Cd complex) by 375-fold.