Faculty Collaboration Database

In vitro sulfoxidation of aldicarb by hepatic microsomes of channel catfish, Ictalurus punctatus. Toxicol Sci 1999 Mar;48(1):67-73

Date

05/20/1999

Pubmed ID

10330685

DOI

10.1093/toxsci/48.1.67

Scopus ID

2-s2.0-0033017209 (requires institutional sign-in at Scopus site)   27 Citations

Abstract

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.

Author List

Perkins EJ, el-Alfy A, Schlenk D

Author

Abir El-Alfy PhD Assistant Dean, Professor in the School of Pharmacy Administration department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aldicarb
Animals
Biotransformation
Blotting, Western
Carbon Monoxide
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System
Ethanol
Ictaluridae
Insecticides
Male
Microsomes, Liver
Muscle, Skeletal
NADP
Oxidation-Reduction
Sulfoxides
beta-Naphthoflavone