RESUMEN
Biochemical markers and ovarian histology were investigated in prespawning females of grass goby (Zosterisessor ophiocephalus) and grey mullet (Mugil cephalus) collected, respectively, in late spring and summer 2000 in four sites of a highly eutrophic brackish ecosystem of central Italy, the Orbetello Lagoon. Exposure to chlorinated and aromatic hydrocarbons was evaluated in fish livers by the somatic liver index (SLI) and by measuring 7-ethoxyresorufin-O-deethylase (EROD) and benzo(a)pyrene monooxygenase (BaPMO) activities. Acetylcholinesterase (AChE) activity was measured in brain and gills to evaluate exposure to organophosphates (OPs) and carbamates (CBs). The gonad somatic index (GSI) was used to confirm ovarian maturation and ovarian histology was investigated as a potential biomarker for environmental effects. Samples from the Western Basin, near a sewage treatment plant (STP) off the town of Orbetello, showed higher SLI values and higher EROD and BaPMO activities than those collected from the Ansedonia Canal (AC) in the Eastern Basin (p<0.05) and respect to those from reference sites: the Albegna River (AR) Delta for grass goby and the Nassa Canal (NC), connected with the sea, for grey mullet both located in the Western Basin as well. Low brain AChE activity was observed in both species from the reference sites (AR and NC) in association with the presence of anomalies in developing oocytes: unexpectedly small in grass goby and irregular disintegrated cytoplasm in grey mullet. The results indicate that the Western Basin is more polluted than the Eastern Basin particularly in the Orbetello where the sewage treatment plant may be a source of aromatic and chlorinated compounds while the Albegna River and the Nassa Canal may be sources of OPs and CBs.
Asunto(s)
Acetilcolinesterasa/análisis , Benzopireno Hidroxilasa/análisis , Citocromo P-450 CYP1A1/análisis , Sistema Enzimático del Citocromo P-450/análisis , Exposición a Riesgos Ambientales , Hidrocarburos Aromáticos/efectos adversos , Hidrocarburos Clorados/efectos adversos , Ovario/patología , Perciformes/anatomía & histología , Perciformes/fisiología , Contaminantes Químicos del Agua/efectos adversos , Acetilcolinesterasa/farmacología , Animales , Benzopireno Hidroxilasa/farmacología , Biomarcadores/análisis , Encéfalo , Citocromo P-450 CYP1A1/farmacología , Sistema Enzimático del Citocromo P-450/farmacología , Femenino , Branquias , ItaliaRESUMEN
Trichloroethylene (TCE) is widely used as an industrial solvent and cleaning fluid. In the present study the toxic effects of TCE inhalation on pulmonary and hepatic biotransformation enzymes in rats have been investigated by assay of aniline hydroxylase (AH), aminopyrine-N-demethylase (APD), benzo-a-pyrene hydroxylase (BH) and glutathione-s-transferase (GST) activities and glutathione (GSH) contents in liver as well as lungs of exposed animals. In both organs phase I and phase II drug metabolizing enzymes have been found to be increased along with decrease in GSH contents following TCE inhalation. Pulmonary as well as hepatic MFO's seem to be activated by inhaled TCE probably in an attempt for its rapid detoxification and reduced glutathione is used during its biotransformation.
Asunto(s)
Administración por Inhalación , Aminopirina N-Demetilasa/farmacología , Anilina Hidroxilasa/farmacología , Benzopireno Hidroxilasa/farmacología , Glutatión Transferasa/farmacología , Solventes/efectos adversos , Tricloroetileno/efectos adversos , Animales , Glutatión/análisis , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/enzimología , Pulmón/patología , Masculino , Ratas , Ratas Wistar , Solventes/administración & dosificación , Tricloroetileno/administración & dosificaciónRESUMEN
Hepatic microsomal xenobiotic metabolizing enzyme activities of laboratory animals can be modulated by Dietary restriction (DR). The modulation of xenobiotic metabolizing enzyme activities can affect the metabolic activation of chemical carcinogens. Acute DR (60% of the food consumption of ad libitum (AL)-fed mice for 7 weeks) reduced the body weights of the male B6C3F1 mice, and increased mouse pulmonary cytochrome P4501A1-dependent BaP metabolizing enzyme activity. The effects of DR on the formation of the specific BaP-DNA adduct, 10-(N2-deoxyguanosinyl)-7,8,9-trihydroxy-7,8,9,10-tetrahydro-BaP (BaP-N2-dG) in mouse lung can be detected by using 32P-postlabeling technique. In both AL- and DR-mice total BaP-DNA adduct formation in lung reached a peak at 48 hours after treatment with [3H]BaP and the in vivo formation of BaP-N2-dG was greater in DR mouse lung than in that of AL-animals by 22%. DR increased in vitro BaP-N2-dG formation by 39% when calf-thymus DNA was incubated with BaP using liver microsomes obtained from DR- or AL-mice as the enzyme source. The formation of the specific BaP-N2-dG adducts, measured by 32P-postlabeling, was only 20% of the total [3H]BaP-DNA adducts as determined by liquid scintillation counting. The increase of BaP-DNA adduct formation in mouse lung was correlated to the enhancement of the mouse pulmonary BaP metabolizing enzyme activity. Our results indicated that the effect of DR on the metabolic activation of BaP in mouse lung was dependent upon the mouse lung cytochrome P4501A1-dependent BaP metabolizing enzymes activities which was significantly increased by DR.
Asunto(s)
Benzo(a)pireno/farmacocinética , Carcinógenos/farmacocinética , Aductos de ADN/metabolismo , Privación de Alimentos/fisiología , Pulmón/metabolismo , Animales , Hidrocarburo de Aril Hidroxilasas/metabolismo , Benzo(a)pireno/metabolismo , Benzopireno Hidroxilasa/metabolismo , Benzopireno Hidroxilasa/farmacología , Biotransformación , Peso Corporal/fisiología , Carcinógenos/metabolismo , Cromatografía en Capa Delgada , Aductos de ADN/análisis , Aductos de ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Pulmón/química , Masculino , Ratones , Microsomas/fisiología , Tamaño de los Órganos , Radioisótopos de Fósforo , Factores de Tiempo , Aumento de PesoRESUMEN
Known cytochrome P450-dependent oxygenase inhibitor ketoconazole (5-50 microM) blocked the murine macrophage-mediated modification of human low density lipoprotein (LDL) as measured by production of thiobarbituric acid-reactive substance, stimulation of [125I]LDL degradation in a fresh set of macrophages and LDL electrophoretic mobility, in a dose-dependent manner with complete inhibition at 30-40 microM. When resident macrophages were incubated with LDL in the presence of metyrapone, methoxsalen and alpha-naphthaflavone at concentrations that have been shown to inhibit the cytochrome P450-dependent oxygenases, there was no change in LDL modification. Induction of benzo[alpha]pyrene hydroxylase activity in macrophages by 24 h incubation with benzo[alpha]pyrene was accompanied by a 1.5-fold increase of LDL modification which has been leveled down by ketoconazole as well as methoxsalen and alpha-naphthaflavone. Furthermore, ketoconazole effectively diminished cell-free LDL oxidation induced by iron, but not copper ions, and reduced the spontaneous and zymosan-stimulated lucigenin-amplified chemiluminescence of macrophages. The data allow us to suggest that ketoconazole inhibits LDL oxidation by acting as an iron chelator and/or inhibitor of prooxidant forms of iron-containing enzymes.