title: Effect of 17beta-estradiol and testosterone on the expression of flavin-containing monooxygenase and the toxicity of aldicarb to Japanese medaka, Oryzias latipes.
abstract: Previous studies in our laboratory indicated gender differences in salinity-enhanced acute toxicity of aldicarb in Japanese medaka with females being more susceptible. In the current study, the effects of the sex steroids, 17beta estradiol (E2) and testosterone (T) on aldicarb toxicity was examined. Adult Japanese medaka were separated by sex and exposed to 100 microg/l E2 or T for 6 days followed by exposure to the 96-h LC50 (0.5 mg/l) of aldicarb. The toxicity of aldicarb to adult males was significantly lowered by E2 and T whereby the mortality percentage was reduced to 23.3 +/- 5.8% and 3.3 +/- 5.8%, respectively, compared to the fish not receiving steroids (46.7 +/- 5.8% mortality). In females, T caused significant reduction in aldicarb toxicity to 16.7 +/- 5.8%, while E2 significantly enhanced the toxicity to 96.7 +/- 5.8% mortality. Since the flavin-containing monooxygenase (FMO) enzyme system had been shown to play a critical role in aldicarb toxicity, the effect of E2 and T on FMO expression was examined. Gill FMO activity showed a direct correlation with the overall toxicity of aldicarb in both male and female medaka. Expression of FMO1-like protein was significantly reduced by T in male livers and gills, and T did not affect the expression of FMOs in female tissues. In contrast, E2 significantly reduced FMO1-like protein expression in male gills and female livers, as well as FMO3 expression in both male and female livers, but significantly increased gill FMO1 expression in females. Since aldicarb acts by inhibiting the enzyme cholinesterase (ChE), the effect of sex hormones on the activity of this enzyme was also examined. In both male and female medaka, T counteracted the inhibitory effect of aldicarb on muscle ChE. In male fish, E2 had similar effects but did not seem to counteract the ChE inhibition in females. In conclusion, E2 and T modulation of aldicarb toxicity in Japanese medaka seems to be mediated via alteration of gill FMO and ChE actitivies.
authors.affiliation: School of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Abir T
authors.initials: AT
authors.lastname: El-Alfy
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlenk
mesh_terms: D000448:Aldicarb / Q000633:toxicity*; D000818:Animals; D002802:Cholinesterases / Q000378:metabolism; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005880:Gills / Q000187:drug effects / Q000201:enzymology; D007306:Insecticides / Q000633:toxicity*; D008136:Longevity / Q000187:drug effects*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009990:Oryzias; D010105:Oxygenases / Q000096:biosynthesis*; D012727:Sex Characteristics; D013739:Testosterone / Q000494:pharmacology*; D023382:Toxicity Tests, Acute
chemical_list: D007306:Insecticides; D013739:Testosterone; D004958:Estradiol; D000448:Aldicarb; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D002802:Cholinesterases