Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka, Oryzias latipes, at high salinity. Toxicol Appl Pharmacol 1998 Sep;152(1):175-83
Date
10/17/1998Pubmed ID
9772213DOI
10.1006/taap.1998.8479Scopus ID
2-s2.0-0031769590 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
In an attempt to understand underlying mechanism(s) of salinity-induced aldicarb toxicity in Japanese medaka (Oryzias latipes), aldicarb uptake, biotransformation, and its effect on acetylcholinesterase (AChE) were examined. Salinity had no effect on aldicarb uptake. However, gill microsomal flavin-containing monooxygenase (FMO) activity and a 57-kDa FMO1-like protein increased as the salinity was raised from 0.15 to 2.0%. Sulfoxidation of 14C-aldicarb by liver and gill microsomal incubations showed ninefold and 1.8-fold increases, respectively, as the salinity was raised from 0.15 to 2.0%. Formation of aldicarb sulfoxide was not affected by incubation with carbon monoxide, indicating that cytochrome P450 (CYP450) was not a primary pathway in the formation of the sulfoxide. Muscle AChE activity showed no significant relationship with salinity, although the IC50 of aldicarb to muscle AChE differed significantly between 6.21 +/- 1. 253 and 2.97 +/- 0.597 microM for 0.15 and 2.0% salinity, respectively. Aldicarb sulfoxide was 40 times more potent than aldicarb in inhibiting muscle AChE in Japanese medaka. Based on these results, we conclude that salinity-induced enhancement of aldicarb toxicity to Japanese medaka might be partly attributed to the upregulation of FMO(s), which, in turn, increase the biotransformation of aldicarb to aldicarb sulfoxide, which is a more potent inhibitor of AChE than aldicarb. In addition, salinity also seems to potentiate the anticholinesterase activity of aldicarb (the parent) through an unknown mechanism.
Author List
El-Alfy A, Schlenk DAuthor
Abir El-Alfy PhD Assistant Dean, Professor in the School of Pharmacy Administration department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylcholinesteraseAldicarb
Animals
Biotransformation
Cytochrome P-450 Enzyme System
Drug Synergism
Gills
Insecticides
Microsomes, Liver
Muscle, Skeletal
Oryzias
Oxygenases
Sodium Chloride
Up-Regulation