Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka, Oryzias latipes, at high salinity.
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.
El-Alfy
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Environmental and Community Health Research, University of Mississippi, University, Mississippi 38677, USA. aelalfyolemiss.edu
Schlenk
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D000110:Acetylcholinesterase / Q000378:metabolism; D000448:Aldicarb / Q000633:toxicity*; D000818:Animals; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004357:Drug Synergism; D005880:Gills / Q000187:drug effects* / Q000201:enzymology; D007306:Insecticides / Q000633:toxicity*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D009990:Oryzias; D010105:Oxygenases / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology*; D015854:Up-Regulation
D007306:Insecticides; D012965:Sodium Chloride; D000448:Aldicarb; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D000110:Acetylcholinesterase