Toxicological Sciences, Vol 48, 67-73, Copyright © 1999 by Society of Toxicology
EJ Perkins, A el-Alfy and D Schlenk
The carbamate pesticide, aldicarb, demonstrates significant acute toxicity
in mammals, birds, and fish, and is readily biotransformed by most
organisms studied. Metabolic products of aldicarb include the more toxic
sulfoxide and the less toxic sulfone as two of the major products. Both the
cytochrome P450 (CYP) and the flavin monooxygenase systems (FMO) are
involved in this process. This study examined the capacities of liver
microsomes of male channel catfish (Ictalurus punctatus), which lack FMO,
to biotransform aldicarb in vitro. In addition, the acetylcholinesterase
inhibitory potencies of aldicarb and its sulfoxide and sulfone derivatives
were determined. For metabolism studies, incubations of [14C]-aldicarb
(0.1mM) were carried out for up to 15-90 min using 1.0 mg/mL of hepatic
microsomal protein. Total NADPH- dependent biotransformation was low (<
3.0% conversion to polar metabolites), and was inhibited by carbon
monoxide. The only metabolite detected was aldicarb sulfoxide (Kmapp = 53.8
+/- 25.3 microM; Vmaxapp = 0.040 +/- 0.007 nmol/min/mg). Treatment of fish
with the CYP modulators beta-naphthoflavone (BNF, 50 mg/kg) and ethanol
(EtOH, 1.0% aqueous) had no effect on sulfoxide production. No correlation
existed between CYP isoform expression (determined by western blot) and
aldicarb sulfoxidation rates, suggesting the involvement of an unmeasured
CYP isoform or involvement of several isoforms with low specificity. This
study indicates that a low rate of bioactivation of aldicarb to aldicarb
sulfoxide may be responsible for the resistance of channel catfish to
aldicarb toxicity relative to that of other piscine species.
ARTICLES
In vitro sulfoxidation of aldicarb by hepatic microsomes of channel catfish, Ictalurus punctatus
Department of Pharmacology, School of Pharmacy, University of Mississippi 38677, USA. eperkins@olemisss.edu
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