The Effects of the Phosphorothioate Insecticide Fenitrothion on Mammalian Cytochrome P450-Dependent Metabolism of Estradiol

Berger, Conney W.; Sultatos, Lester G.

doi:10.1093/toxsci/37.2.150

Cited by 6 publications

(5 citation statements)

References 19 publications

(29 reference statements)

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“…Exposure to fenitrothion might change estradiol biotransformation by inhibition of certain CYP enzymes [4]. It has also been revealed that both chlorpyrifos-oxon and carbaryl inhibited the esterase(s) necessary for the primary step in permethrin metabolism in the human liver [15].…”

Section: Discussionmentioning

confidence: 99%

Effects of several organophosphates on hepatic cytochrome P450 activities in rats

Abdou

Elbadawy

Khalil

et al. 2020

The Journal of Veterinary Medical Science

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Four commonly used organophosphates (fenitrothion, dichlorvos, chlorpyrifos, and trichlorfon) were orally administered to male Sprague-Dawley rats for five days in order to explore their effects on the activities of liver cytochrome P450 (CYP). In addition, Michaelis-Menten kinetics of the metabolic reactions catalyzed by liver CYPs were analyzed following the addition of these compounds to the assay system to examine their potential inhibitory effects on liver CYPs activities. These reactions included ethoxyresorufin O-deethylation, midazolam 4-hydroxylation, tolbutamide hydroxylation, and bufuralol 1'-hydroxylation for CYP1A, 3A, 2C, and 2D activities, respectively. Total CYP content was also examined after oral administration of each organophosphate. Results revealed that oral giving of fenitrothion inhibited significantly CYP1A and 3A activities while elevated activity of CYP2C. Fenitrothion is a potent inhibitor for CYP1A and 2C with Ki values of 0.42 and 36.1 μM, respectively but had a weak inhibitory effect on CYP2D and 3A with Ki values of 290 and 226 μM, respectively. Chlorpyrifos is a potent inhibitor of CYP1A with Ki 0.24 μM and moderately inhibited CYP2C or 3A with Ki values of 84.8 and 77.7 μM, respectively. On the other hand, dichlorvos and trichlorfon caused extremely low or negligible inhibition of different CYP activities. From these results, it is concluded that both fenitrothion and chlorpyrifos may increase the toxicity of chemicals in environmental living organisms through their potent inhibitory effects on these CYP activities, but dichlorvos and trichlorfon may not.

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Section: Discussionmentioning

confidence: 99%

Effects of several organophosphates on hepatic cytochrome P450 activities in rats

Abdou

Elbadawy

Khalil

et al. 2020

The Journal of Veterinary Medical Science

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“…Both the ALS inhibitor‐resistant and ‐susceptible accessions of the Echinochloa spp. were treated with or without fenitrothion at 500 g ai ha −1 5 h prior to the application of the herbicides (Berger & Sultatos ; Lopez‐Martinez et al ). Then, the ALS inhibitors, azimsulfuron, penoxsulam and bispyribac‐sodium, were applied to the plants at concentrations from x1/8 to x8 of their recommended dose at the fourth‐leaf stage, as in the whole‐plant assay described above.…”

Section: Methodsmentioning

confidence: 99%

Cross‐resistance of Echinochloa species to acetolactate synthase inhibitor herbicides

Song

Lim

Yook

et al. 2017

Weed Biology and Management

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This study was conducted to evaluate the cross‐resistance of acetolactate synthase (ALS) inhibitors with different chemistries, specifically azimsulfuron (sulfonylurea), penoxsulam (triazolopyrimidine sulfonanilide) and bispyribac‐sodium (pyrimidinyl thio benzoate), in Echinochloa oryzicola and Echinochloa crus‐galli that had been collected in South Korea and to investigate their herbicide resistance mechanism. Both Echinochloa spp. showed cross‐resistance to the ALS inhibitors belonging to the above three different chemistries. In a whole plant assay with herbicides alone, the resistant/susceptible ratios for azimsulfuron, penoxsulam and bispyribac‐sodium were 12.6, 28.1 and 1.9 in E. oryzicola and 21.1, 13.7 and 1.8 in E. crus‐galli, respectively. An in vitro ALS enzyme assay with herbicides showed that the I 50‐values of the resistant accessions were approximately two‐to‐three times higher than the susceptible accessions, with no statistical difference, suggesting that the difference in ALS sensitivity cannot explain ALS inhibitor resistance in Echinochloa spp. for azimsulfuron, penoxsulam and bispyribac‐sodium. A whole plant assay with fenitrothion showed that the GR 50‐values significantly decreased in both the resistant E. oryzicola and E. crus‐galli accessions when azimsulfuron, penoxsulam and bispyribac‐sodium were applied with the P450 inhibitor, while no significant decrease was observed in the susceptible accessions when the P450 inhibitor was used. Thus, these results suggest that ALS inhibitor cross‐resistance for azimsulfuron, penoxsulam and bispyribac‐sodium is related to enhanced herbicide metabolism.

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“…Liehr et al (26) reported the importance of the relationship between the altered metabolic characteristics and the incidence of estrogen-induced tumors. Exposure to organophosphorus insecticide might alter E 2 metabolism by inhibition of certain P450 isozymes (27). If the chemicals in our environment alter estrogen metabolism, the incidence of estrogenic cancers might be varied.…”

Section: Discussionmentioning

confidence: 99%

Quantitation of Catechol Estrogens and Their N-Acetylcysteine Conjugates in Urine of Rats and Hamsters

Nakagomi

Suzuki

2000

Chem. Res. Toxicol.

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A method for the analysis of N-acetylcysteine conjugates of catechol estrogens [catechol estrogen mercapturates (CE SRs)], which are likely to be urinary markers of estrogen-induced tumors, was established in this study. The characteristics of the method that was established were (1) cleanup of urine using the immunoaffinity column of CE SRs, (2) detection of catechol estrogens (CEs) and CE SRs by electrochemical detection, which provided the high specificity, and (3) stability of CE SRs through the cleanup. Using this method, the simultaneous quantitation of 2-hydroxy-17beta-estradiol (2-OHE(2)), 4-hydroxy-17beta-estradiol (4-OHE(2)), 2-hydroxyestrone (2-OHE(1)), 4-hydroxyestrone (4-OHE(1)), 2-hydroxyestrone 1-N-acetylcysteine thioether (2-OHE(1) 1SR), 2-hydroxyestrone 4-N-acetylcysteine thioether (2-OHE(1) 4SR), and 4-hydroxyestrone 2-N-acetylcysteine thioether (4-OHE(1) 2SR) in the range of 1-15 ng was performed. We first demonstrated the presence of CE SRs, 2-OHE(1) 1SR and 2-OHE(1) 4SR, in urine from rats treated intraperitoneally with 17beta-estradiol (E(2)) at a dose of 5 mg/kg. In female rats, the amount of 2-OHE(1) 1SR was several-fold greater than that of 2-OHE(1) 4SR, while the presence of 4-OHE(1) 2SR was not confirmed. The level of CEs and CE SRs in male rats was approximately (1)/(2)-(1)/(20) of that in female rats. The excretion rate following administration of 2-OHE(1) at 2 mg/kg and that following the administration of 4-OHE(1) at 2 mg/kg were different in female rats. In addition, 4-OHE(1) 2SR was present in the urine of male Syrian hamsters treated intraperitoneally with E(2), whereas it was absent in rats.

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The Effects of the Phosphorothioate Insecticide Fenitrothion on Mammalian Cytochrome P450-Dependent Metabolism of Estradiol

Cited by 6 publications

References 19 publications

Effects of several organophosphates on hepatic cytochrome P450 activities in rats

Effects of several organophosphates on hepatic cytochrome P450 activities in rats

Cross‐resistance of Echinochloa species to acetolactate synthase inhibitor herbicides

Quantitation of Catechol Estrogens and Their N-Acetylcysteine Conjugates in Urine of Rats and Hamsters

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