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.
Environmental and Community Health Research, University of Mississippi, University, Mississippi 38677, USA. aelalfyolemiss.edu
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El-Alfy
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Schlenk
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