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Hepatic enzyme induction, an inherent defense system against xenobiotics, is known to simultaneously affect endocrine system functions in mammals under specific conditions, particularly thyroid hormone (TH) regulation. While this phenomenon has been studied extensively, the pathway leading to this indirect thyroid effect in mammals has unclear applicability to amphibians, despite the importance of amphibian species in assessing thyroid-disruptive chemicals. Here, we investigated the effects of three well-known mammalian enzyme inducers-β-naphthoflavone (BNF), pregnenolone carbonitrile (PCN), and sodium phenobarbital (NaPB)-on the gene expression of phase-I and phase-II metabolizing enzymes in Xenopus laevis tadpoles. Waterborne exposure to BNF and PCN significantly induced the expression of both phase-I (cytochrome P450, CYP) and phase-II enzymes (UDP-glucuronosyltransferase, UGT and sulfotransferase, SULT), but in different patterns, while NaPB exposure induced CYP2B expression without affecting phase-II enzymes in tadpoles, in contrast to mammals. Furthermore, an ex vivo hepatic enzyme activity assay confirmed that BNF treatment significantly increased phase-II metabolic activity (glucuronidation and sulfation) toward TH. These results suggest the potential for certain mammalian enzyme inducers to influence TH clearance in X. laevis tadpoles. Our findings provide insights into the profiles of xenosensing activity and enzyme induction in amphibians, which can facilitate a better understanding of the mechanisms of indirect effects on the thyroid system via hepatic enzyme induction in nonmammalian species., (© 2024 John Wiley & Sons Ltd.)

Based on the experimental subcooled liquid vapor pressures (P L ) of 17 polychlorinated naphthalene (PCN) congeners, one type of three-dimensional quantitative structure-activity relationship (3D-QSAR) models, comparative molecular similarity indices analysis (CoMSIA), was constructed with Sybyl software. Full factor experimental design was used to obtain the final regulation scheme for PCN, and then carry out modification of PCN-2 to significantly lower its P L . The contour maps of CoMSIA model showed that the migration ability of PCN decreases when the Cl atoms at the 2-, 3-, 4-, 5-, 6-, 7- and 8-positions of PCNs are replaced by electropositive groups. After modification of PCN-2, 12 types of new modified PCN-2 compounds were obtained with lnP L values two orders of magnitude lower than that of PCN-2. In addition, there are significant differences between the calculated total energies and energy gaps of the new modified compounds and those of PCN-2.

Sulfamethoxazole (SMX), as a common sulfonamide antibiotic, was reported to affect conventional anaerobic denitrification. This study presented effects of SMX on aerobic denitrification by an aerobic denitrifier strain Pseudomonas stutzeri PCN-1. Results demonstrated serious inhibition of N 2 O reduction as SMX reached 4μg/L, leading to higher N 2 O emission ratio (251-fold). Increase of SMX (∼8μg/L) would induce highest nitrite accumulation (95.3mg/L) without reduction, and severe inhibition of nitrate reduction resulted in lower nitrate removal rate (0.15mg/L/h) as SMX reached 20μg/L. Furthermore, corresponding inhibition of SMX on denitrifying genes expression (nosZ>nirS>cnorB>napA) was found with a time-lapse expression between nosZ and cnorB. Meanwhile, the decline in electron transport activity and active microbial biomass of strain PCN-1 was revealed. The insight into mechanism of SMX influence on aerobic denitrifier is of particular significance to upgrade nitrogen removal process in antibiotics-containing wastewater treatment plant., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Rat liver microsomes were examined for their ability to oxidize the mycotoxin ochratoxin A (OTA) to 4(R)-4-hydroxyochratoxin A [(R)-4-OH-OTA] and 4(S)-4-hydroxyochratoxin A [(S)-4-OH-OTA] and to induce OTA-dependent lipid peroxidation. Microsomes isolated from rats pretreated with pregnenolone-16 alpha-carbonitrile greatly induced both (R)-4-OH-OTA and (S)-4-OH-OTA formation whereas isoniazid pretreatment primarily induced (S)-4-OH-OTA. (R)-4-OH-OTA and (S)-4-OH-OTA formation showed significant differences with respect to pH optima, effect of antioxidants, and iron chelators. (R)-4-OH-OTA showed a pH optimum of 6.5 and was not inhibited by the antioxidants butylated hydroxyanisole or N,N-diphenyl-1,4-phenylenediamine or the iron chelators. Desferal or bathophenanthrolinedisulfonic acid. In contrast, both (S)-4-OH-OTA and lipid peroxidation showed a pH optimum of 7.0 and both activities were sensitive to inhibition by the above antioxidants and iron chelators. Lipid peroxidation was not involved in (S)-4-OH-OTA formation since addition of linoleic acid hydroperoxide to microsomes did not give rise to (S)-4-OH-OTA. Cytochrome P450 appeared to be essential since other hemoproteins like horseradish peroxidase and hemoglobin were ineffective in metabolizing OTA in the presence of hydroperoxides. The results suggest that (R)-4-OH-OTA is formed by normal mixed-function oxidation but that (S)-4-OH-OTA formation may involve free iron. It is likely that an active Fe2(+)-oxygen complex, formed via NADPH-cytochrome P450 reductase and cytochrome P450-dependent reduction of free Fe3+ followed by oxygen binding, serves as the species inducing lipid peroxidation and at least part of (S)-4-OH-OTA formation.