RESUMO
Mercury in contaminated soils and sediments could be extracted by various chemical reagents in order to determine the different mercury species and partitions, providing useful information of toxicology, bioavailability and biogeochemical reactivity. Unfortunately, at present, neither specific extractants nor standard protocols exist for the isolation of particular mercury species. Although there has been considerable research focused on reagents for extracting mercury species, there is still little consensus. Thus, workers are advised to select the most appropriate reagent based on the nature of their sample, and to take all possible steps to validate the analyses performed. Therefore, the aim of this paper is to review the current reagents used for determining total mercury and its speciation as well as fractionation such as methylmercury, ethylmercury, elemental mercury, mercury sulphide and organically bound mercury by supposed selective (one reagent) and sequential (several reagents) extractions. The gathering information presented here bring to light the need for standard protocol for which the used chemical reagents should take into account the particular chemistry of mercury associated with specific properties of soil and sediment. Beside this required scheme, appropriate reference materials are also demanded.
Assuntos
Acetaminofen/farmacologia , Gangliosídeo Galactosiltransferase/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Acetaminofen/administração & dosagem , Analgésicos não Narcóticos/farmacologia , Animais , Esquema de Medicação , Gangliosídeo Galactosiltransferase/biossíntese , Humanos , Ratos , Regulação para Cima/efeitos dos fármacosRESUMO
Excretion of lipophilic cationic toxic compounds from the interior of the hepatocyte to the bile is mediated by P-Glycoprotein. It is an integral protein located in the bile canaliculi. The present work study the hepatic expression of P-Glycoprotein in different models of experimental liver disease: Acute paracetamol intoxication, extrahepatic cholestasis and cholestasis followed by acute paracetamol intoxication. mRNA was isolated from liver tissue, and the expression of Pg-p was assessed by Northern blot. It is concluded that the hepatic expression of mdr1b is increased in the experimental liver diseases when compared to controls. On the other hand, mdr2 expression was similar between the different groups
Assuntos
Animais , Masculino , Ratos , Acetaminofen , Analgésicos não Narcóticos , Colestase Extra-Hepática , Regulação da Expressão Gênica , Genes MDR , Hepatopatias , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Acetaminofen , Doença Aguda , Analgésicos não Narcóticos , Bile , Northern Blotting , Proteínas de Transporte , Colestase Extra-Hepática , Modelos Animais de Doenças , Overdose de Drogas , Regulação da Expressão Gênica , Genes MDR , Hepatócitos , Hepatopatias , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Ratos Wistar , RNA MensageiroRESUMO
Excretion of lipophilic cationic toxic compounds from the interior of the hepatocyte to the bile is mediated by P-Glycoprotein. It is an integral protein located in the bile canaliculi. The present work study the hepatic expression of P-Glycoprotein in different models of experimental liver disease: Acute paracetamol intoxication, extrahepatic cholestasis and cholestasis followed by acute paracetamol intoxication. mRNA was isolated from liver tissue, and the expression of Pg-p was assessed by Northern blot. It is concluded that the hepatic expression of mdr1b is increased in the experimental liver diseases when compared to controls. On the other hand, mdr2 expression was similar between the different groups (AU)
Assuntos
Animais , Masculino , Ratos , Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Colestase Extra-Hepática/induzido quimicamente , Regulação da Expressão Gênica , Genes MDR/genética , Hepatopatias/induzido quimicamente , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Acetaminofen/metabolismo , Doença Aguda , Analgésicos não Narcóticos/metabolismo , Bile/metabolismo , Colestase Extra-Hepática/metabolismo , Northern Blotting , Proteínas de Transporte/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Genes MDR/efeitos dos fármacos , Hepatócitos , Hepatopatias/metabolismo , Overdose de Drogas , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos WistarRESUMO
The aim of the present paper is to establish the possible role of serum TNF in the pathophysiology of three experimental models of liver injury: paracetamol intoxication, cholestasis followed by paracetamol intoxication and cholestasis. We concluded that under our experimental conditions the serum TNF-alpha levels were not responsible for the inflammatory phenomena described in our previous paper as apoptosis.
Assuntos
Acetaminofen/toxicidade , Analgésicos não Narcóticos/toxicidade , Colestase/induzido quimicamente , Nefropatias/fisiopatologia , Fator de Necrose Tumoral alfa/fisiologia , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Colestase/fisiopatologia , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/químicaRESUMO
Theaim of the present paper is to establish the possible role of serum TNF in the pathophysiology of three experimental models of liver injury: paracetamol intoxication, cholestasis followed by paracetamol intoxication and cholestasis. We concluded that under our experimental conditions the serum TNF-alpha levels were not responsible for the inflammatory phenomena described in our previous paper as apoptosis.
RESUMO
The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation. After 7 days animals were injected with paracetamol (BDL-APAP group). Sham-operated rats were injected at day 7 with paracetamol (APAP group). Cholestatic and sham-operated rats injected with vehicle (BDL and control groups). UDP-GT activity was measured by a kinetic method for different substrates. Microsomal membrane phospholipid composition, cholesterol content and ultrastructure were determined. BDL-APAP group showed an increment in the UDP-GT activity except for chloramphenicol, morphine and paracetamol if compared to controls and to BDL group. The same increment was observed when BDL-APAP was compared to APAP except for chloramphenicol and lorazepam. Between BDL and APAP groups similar levels of activity were detected except for paracetamol. Microsomal phospholipid profile: phosphatidylcholine showed the lowest content in the BDL group, with a significant recovery in the BDL-APAP and APAP groups. Phosphatidylserine was markedly decreased in the APAP group compared to the rest and phosphatidylinositol was decreased in all the groups if compared to control values. An increment of phosphatidylethanolamine was seen in the APAP and BDL-APAP groups if compared to BDL and control values. A significant increment of microsomal cholesterol content was seen in BDL. Under these conditions, a different lipid microenvironment is produced, resulting in an increment of the enzyme activity for a variety of substrates.
Assuntos
Acetaminofen/intoxicação , Analgésicos não Narcóticos/intoxicação , Colestase/metabolismo , Glucuronosiltransferase/metabolismo , Microssomos Hepáticos/metabolismo , Fosfolipídeos/metabolismo , Acetaminofen/sangue , Analgésicos não Narcóticos/sangue , Animais , Ductos Biliares/metabolismo , Ligadura , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The aim of the present paper is to establish possible disturbances in benzodiazepines glucuronidation in two experimental models of liver injury: paracetamol acute intoxication and cholestasis followed by paracetamol acute intoxication. We concluded that, despite the alterations observed in liver microsomal lipid profile, glucuronidation remained similar to controls in paracetamol intoxicated rats. On the contrary, cholestatic animals followed by paracetamol intoxication showed an increment in the glucuronidation of the utilized substrated.
Assuntos
Benzodiazepinas/metabolismo , Colestase/metabolismo , Glucuronosiltransferase/metabolismo , Hepatopatias/metabolismo , Acetaminofen , Doença Aguda , Analgésicos não Narcóticos , Animais , Doença Hepática Induzida por Substâncias e Drogas , Colestase/induzido quimicamente , Hepatopatias/enzimologia , Masculino , Ratos , Ratos WistarRESUMO
The aim of the present paper is to establish possible disturbances in benzodiazepines glucuronidation in two experimental models of liver injury: paracetamol acute intoxication and cholestasis followed by paracetamol acute intoxication. We concluded that, despite the alterations observed in liver microsomal lipid profile, glucuronidation remained similar to controls in paracetamol intoxicated rats. On the contrary, cholestatic animals followed by paracetamol intoxication showed an increment in the glucuronidation of the utilized substrated.
RESUMO
The liver is responsible for the most important metabolic pathway of non polar compounds. The aim of the present work was to study the p-nitrophenol glucuronidation and its relationship with lipidic composition of microsomal membrane in a model of hepatic portal hypertension and hepatocellular damage induced by monocrotaline. A global increment in liver microsomal phospholipids as well as changes in the phospholipid pattern (phosphatidylethanolamine and sphingomyelin increased up to 156 +/- 13 and 195 +/- 14% respectively) were detected in monocrotaline intoxicated rats when it were compared to control rats. The microsomal cholesterol content showed a decrease in monocrotaline intoxicated rats. (4.1 +/- 0.7 against 6.6 +/- 1.5 micrograms/mg of microsomal protein, in control rats). When p-nitrophenol activity was measured, Km from monocrotaline intoxicated rats was 0.137 mM, and Vmax was 2.9 nmol of p-nitrophenol/mg microsomal protein since in control group Km was 0.322 mM, and Vmax was 4.5 nmol of p-nitrophenol/mg microsomal protein. It is concluded that monocrotaline intoxicated rats showed a different behavior in the kinetics of p-nitrophenol UDP-glucuronyltransferase, as well as a different microsomal lipidic profile, when compared to control group.