[The role of nuclear receptors in cytochrome P-450 induction by xenochemicals].

This review summarizes recent findings indicating that members of the orphan nuclear receptor superfamily regulate the synthesis of their CYP genes which code CYP enzymes involved in metabolism of endogenous and exogenous compounds. The foreign compounds metabolism and the role played by individual cytochrome P450 (CYP) enzymes in the activation and detoxification of xenochemicals prevalent in the environment are important areas of molecular pharmacology and toxicology. The advances in our understanding of the mechanisms through which foreign chemicals impact on these CYP-dependent metabolic processes have been made during the past years.

Hepatocellular peroxisome proliferation and DNA synthesis in Wistar rats treated with herbicide fluazifop.

The aim of this study was to determine the effect of herbicide fluazifop, on the early occurring changes in rat liver regarded as hepatic markers of peroxisome proliferators (PPs). Fluazifop was administered orally to male Wistar rats at increasing doses from 5.6 to 891 mg/kg body weight per day for 1, 2, 4, 7 and 14 consecutive days and peroxisome proliferation, induction of some peroxisome-associated enzymes and mitogenesis (S-phase, M-phase and percentage of binucleated hepatocytes) were studied.

[Effect of diclofop on the activity of some drug-metabolizing enzymes in the liver of male Wistar rats].

The study was designed to determine whether diclofop, introduced to environment as herbicide, would exert properties of chemical inducers of rat liver monooxygenase system related to CYP1A and CYP2B isozymes. For this purpose, the effect of diclofop on 7-etoxyresorufin O-dealkylase and p-nitroanisole O-demethylase activities specific for CYP1A as well as on CYP2B mediated 7-pentoxyresorufin O-dealkylase activity was studied in male Wistar rats. This biochemical method permits to determine whether tested compound belongs to one of two main types of chemical inducers.

Studies of early hepatocellular proliferation and peroxisomal proliferation in Wistar rats treated with herbicide diclofop.

A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight.

Early hepatic changes in rats induced by permethrin in comparison with DDT.

In this study permethrin [(3-phenoxyphenyl)-methyl-3-(2,2-dichloroethenyl)-2,2-dim ethylcyclopropanecarboxylate] and DDT [1,1-(2,2,2 trichloroethylidene)-bis-(4-chlorobenzene)] were compared in rats for their effects on early hepatic changes, proposed in the literature to be useful endpoints in screening for non-genotoxic hepatocarcinogenesis and/or liver tumour promotion. We compared the effects of both insecticides on the following endpoints: hepatomegaly, mitogenesis (DNA synthesis, mitotic activity, percentage of binuclear cells) and liver pathology. Male Wistar rats received permethrin (PERM) or DDT in one, three, five and 14 daily oral doses (at 24-h intervals) equivalent to 1/10 LD50.