Excretion and metabolism of phenol, 4-nitrophenol and 2-methylphenol by the frogsRana temporariaandXenopus laevis

Abstract

1. Rana and Xenopus excrete 90-95% dose, and metabolize 50-65% dose of phenol, 4-nitrophenol and 2-methylphenol within 24 h, to about the same extent. 2. Kinetic data for the excretion of phenols from both species fit a two-compartment model. The elimination constants of Rana and Xenopus are not significantly different. 3. Metabolism is mostly conjugation by glucuronidation and sulphation of the original phenols. Additionally, oxidations leading to dihydroxyphenols and benzoic acid from 2-methylphenol, and reduction of 4-nitrophenol occur, followed by conjugation. 4. There is an important difference between the metabolite patterns of Rana and Xenopus in that the latter is unable to glucuronidate phenols. As the amount of metabolites produced is similar in both species. Xenopus compensates for its inability to glucuronidate by increasing other metabolites.

Bioconcentration and metabolism of pesticides and industrial chemicals in the frog

“…100) Furthermore, the species difference in the relevant enzyme activity may result in the preferential formation of these conjugates. Glu conjugates were detected for the metabolism of phenytoin in R. pipiens, 113) cypermethrin in liver homogenates of R. temporaria, 82) and aldosterone in R. catesbeiana, 118) while Sulf ones were predominant for T 3 in R. catesbeiana, 119) pyrene, 92) tetrabromobisphenol A 95) and phenols 99) in X. laevis. In contrast to the oxidation and conjugation reactions as above, other metabolic pathways have scarcely been reported.…”

“…99) Epoxidation of cyclodiene insecticides, aldrin and chlordane, was observed by using the hepatic microsomal fraction of adult X. laevis, together with hydroxylation at the 1-position of the latter.…”

“…81) Enzymatic oxidation has been most frequently reported for many chemicals, with the reaction profiles classified to hydroxylation of the aromatic ring and alkyl group, dealkylation, ep-oxidation, and sulfur oxidation. The ring oxidation to form the corresponding quinol, catechol, and resorcinol was reported for phenol, 99,107) 3-nitrophenol, 100) 4-nitrophenol, and 2-methylphenol, 99) all of which were intraperitoneally injected into adult R. temporaria or X. laevis. Since the oxo-iron (IV) porphyrin π-cation radical is considered to be a reactive species in catalytic oxidation by CYP and has an electrophilic nature, 108) the regioselectivity in ring hydroxylation can be qualitatively explained by the electron density in the highest occupied molecular orbital (HOMO) of a chemical; the higher electron density is located, the more hydroxylation proceeds.…”

“…Reductive metabolism of nitrophenols in R. temporaria and X. laevis was rationally presumed by the detection of their acetylamino derivatives, 99,100) but the information on corresponding reductases is very limited. No nitro reduction of 4-nitrobenzoic acid was confirmed by using liver homogenates of R. pipiens, R. catesbeiana and B. marinus, while these species could reduce the azo moiety of the antibiotic neoprontosil in the presence of cofactors such as NADPH under N 2 .…”

“…The co-injection of saccharo-1,4-lactone, a β-glucuronidase inhibitor, led to the formation of a Glu conjugate, indicating that the action of β-glucuronidase masked the formation of the conjugate. Phenols are susceptible to Glu and Sulf conjugations with their relative preference depending on ring substituents, based on the metabolism stud- ies using R. temporaria (% Glu, % Sulf): phenol (18%, 25%), 4-nitrophenol (13%, 48%), 2-methylphenol (8%, 33%), 99) and 3-nitrophenol (57%, 26%). 100) Furthermore, the species difference in the relevant enzyme activity may result in the preferential formation of these conjugates.…”