Biologically Active Conjugates of Drugs and Toxic Chemicals

Kauffman, Frederick C.; Zaleski, Jan; Thurman, R. G.; Kwei, Gloria Y.

doi:10.1007/978-3-642-78429-3_12

Cited by 5 publications

(3 citation statements)

References 71 publications

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“…Limited studies have reported the serum concentrations of p-NEOs and m-NEOs in humans. ,− Our results on serum levels of NEOs agree with those monitored previously in whole blood samples (median Σ 11 NEOs: 7.75 ng/mL) and in periodontal blood samples (median Σ 9 NEOs: 6.87 ng/mL) collected from Guangzhou. , However, the median sum concentration of seven p-NEOs (including ACE, IMI, CLO, THD, and THM) in human serum samples collected from Wuxi city in China was 0.026 ng/mL, which is 2 orders of magnitude lower than that of Σp-NEOs_ total (median: 2.54 ng/mL) found in our study, mostly because our study used enzymatic hydrolysis while the other study did not. Therefore, our study highlights the significance of quantification of free and conjugated forms of NEOs.…”

Section: Resultssupporting

confidence: 90%

“…Several studies have presented evidence that conjugated forms of chemicals may elicit greater toxicity. Kauffman et al summarized that some chemicals may generate more potent carcinogenic compounds via a Phase II conjugation reaction . For example, the metabolic transformation of 2-naphthylamine produces N -hydroxy-N-glucuronide that decomposes in urine to hydroxylamine and its protonated nitrogen ions, which easily react with DNA to cause bladder cancer .…”

Section: Resultsmentioning

confidence: 99%

“…Kauffman et al summarized that some chemicals may generate more potent carcinogenic compounds via a Phase II conjugation reaction. 41 For example, the metabolic transformation of 2-naphthylamine produces N-hydroxy-N-glucuronide that decomposes in urine to hydroxylamine and its protonated nitrogen ions, which easily react with DNA to cause bladder cancer. 42 Furthermore, Feng et al investigated possible impacts of free and conjugated forms of phthalate metabolites on male fertility and they showed that in the fertile group, the ratios of free forms to conjugated forms of monoethyl phthalate and mono-2-ethylhexyl phthalate were higher than those in the infertile group, indicating a higher efficiency of Phase II metabolic transformation in the infertile group.…”

Section: Associations Between Oxidative Stress and Serum Neos Levelsmentioning

confidence: 99%

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Insights into Free and Conjugated Forms of Neonicotinoid Insecticides in Human Serum and Their Association with Oxidative Stress

et al. 2023

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Following exposure, neonicotinoid insecticides (NEOs) can be metabolized by both Phase I and Phase II reactions catalyzed by human cytochrome P450 enzymes. However, toxicities of parent NEOs and their metabolites are still unclear, and little is known about biotransformation rates and pathways of NEOs in humans. In this study, 98 serum samples collected in China were analyzed for free, conjugated and total forms of six parent NEOs (i.e., acetamiprid (ACE), imidacloprid (IMI), clothianidin (CLO), thiacloprid (THD), thiamethoxam (THM), and dinotefuran (DIN)) and four metabolites (i.e., N-desmethyl-acetamiprid (N-dm-ACE), 1-methyl-3-(tetrahydro-3-furylmethyl) (DIN-U), 5-hydroxy-imidacloprid (5-OH-IMI), olefin-imidacloprid (Of-IMI)). NEOs and their metabolites were detected in all serum samples, and the total median concentrations of free, conjugated, and total forms of 10 NEOs were 2.04, 2.01, and 5.12 ng/mL, respectively. Conjugated forms of NEOs accounted for only half (53%) of the total forms of NEOs. Based on the profiles of Phase I and Phase II metabolites of NEOs in serum, it was found that age is a determinant in Phase I metabolism of DIN and Phase II metabolism of IMI. The Phase II metabolites of NEOs are associated with oxidative DNA damage, and the conjugated forms of IMI, DIN, and 5-OH-IMI in serum were significantly positively correlated with oxidative stress. Overall, the amount of NEOs present in conjugated forms in human serum was determined to document the existence of a considerable proportion of free forms of these insecticides.

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