RESUMEN
Experiments on newborn rats demonstrated that hepatic monooxygenase system inductors, such as phenobarbital, benzonal, zixorin, increased their body weight, absolute and relative mass of newborn lungs when applied antenatally in contrast to dexamethasone which decreased the above parameters. The inductors increased pulmonary and hepatic phospholipid levels, which suggests that they are superior to dexamethasone in this respect.
Asunto(s)
Barbitúricos/farmacología , Compuestos de Bencidrilo/farmacología , Dexametasona/farmacología , Oxigenasas/efectos de los fármacos , Fenobarbital/farmacología , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Inducción Enzimática/efectos de los fármacos , Femenino , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Oxigenasas/biosíntesis , Fosfolípidos/metabolismo , Embarazo , RatasRESUMEN
The antenatal use of nicotinamide and especially alpha-tocopherol in the experiments with premature newborn rats caused a significant decrease in the rate of lipid peroxidation and an increase in catalase activity both in the maternal body and in fetal lung tissue. It is suggested that the drugs can be used to prevent the development of membrane-destructive processes in the fetal and neonatal lung.
Asunto(s)
Antioxidantes , Peroxidación de Lípido/efectos de los fármacos , Pulmón/efectos de los fármacos , Niacinamida/farmacología , Efectos Tardíos de la Exposición Prenatal , Vitamina E/farmacología , Líquido Amniótico/efectos de los fármacos , Líquido Amniótico/metabolismo , Animales , Animales Recién Nacidos , Femenino , Pulmón/metabolismo , Placenta/efectos de los fármacos , Placenta/metabolismo , Embarazo , RatasRESUMEN
It is stated that phenobarbital used as the most potent inductor of the monoxygenase enzymic system of the liver in different pathologies has substantial side effects. In this connection the search of active inductive agents devoid of phenobarbital deficiencies is an important issue. Zixorene, a Hungarian drug developed to solve the problem, is weak as an inductor and has deficiencies of its own. A fitting substitute for phenobarbital is benzonal which is not inferior to phenobarbital in inductive activity but lacks its drawbacks. It is used both as a hypobilirubinemic agent and a drug restoring a disordered monohygenase system of the liver in different pathologies. Benhonal is metabolized in the gastrointestinal tract and the liver generating an active metabolite of phenobarbital. It is suggested that slow formation of phenobarbital in small quantities determines its more optimal interaction with the corresponding hepatic receptors resulting in the appearance of a marked inductive action while side effects are significantly decreased.
Asunto(s)
Anticonvulsivantes/farmacología , Barbitúricos/farmacología , Hígado/efectos de los fármacos , Oxigenasas/efectos de los fármacos , Fenobarbital/farmacología , Animales , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapéutico , Barbitúricos/farmacocinética , Barbitúricos/uso terapéutico , Inducción Enzimática/efectos de los fármacos , Humanos , Hígado/enzimología , Oxigenasas/biosíntesis , Fenobarbital/farmacocinética , Fenobarbital/uso terapéuticoAsunto(s)
Bilis/metabolismo , Colorantes , Hígado/fisiopatología , Peritonitis/fisiopatología , Absorción , Factores de Edad , Anciano , Biotransformación/fisiología , Colorantes/farmacocinética , Humanos , Hígado/efectos de los fármacos , Pruebas de Función Hepática/métodos , Persona de Mediana EdadRESUMEN
In male rabbits with experimental acute hepatitis, acute renal insufficiency, diffuse peritonitis, Staphylococcus sepsis and thermic burns and also in patients with diseases of the nervous system one could observe prolongation of the half-elimination period (T1/2) and decrease of metabolic clearance of antipyrine. Benzonal (50 mg/kg orally for 3 days) normalized indices of antipyrine test. Similar results were obtained in patients with diseases of the nervous system (epilepsy, rheumatic vasculitis of the cerebral vessels with convulsive syndrome).
Asunto(s)
Barbitúricos/farmacología , Hígado/efectos de los fármacos , Animales , Antipirina/farmacocinética , Barbitúricos/uso terapéutico , Biotransformación/efectos de los fármacos , Evaluación de Medicamentos , Evaluación Preclínica de Medicamentos , Humanos , Hígado/metabolismo , Masculino , Conejos , Factores de TiempoRESUMEN
It was found that in experimental peritonitis the activities of hepatic amidopyrine-N-dimethylase, aniline hydroxylase and NADPN cytochrome-C-reductase as well as the contents of cytochromes P-450 and B5 in the microsomal fraction of the liver significantly decrease and also there is prolongation of the half-life and reduction of the clearance of antipyrine. Similar changes in the drug pharmacokinetic were revealed also in the patients with developed and diffuse peritonitis, their degree being more significant in patients hospitalized in the toxic phase and especially in the terminal phase of the disease.
Asunto(s)
Antipirina/farmacocinética , Hígado/enzimología , Peritonitis/enzimología , Adulto , Animales , Semivida , Humanos , Masculino , Persona de Mediana Edad , Conejos , Ratas , Factores de TiempoRESUMEN
The duration of action and the pharmacological activity of hexenal, phentanyl, meprobamate, corazole and sodium barbital were studied in male rats with acute intestinal ileus (AII) 12, 24, 48 and 72 hours after its reproduction and 24 hours after surgical treatment. A significant enhancement of the action of the studied drugs due to repression of their metabolism in the liver was observed in AII. The experimental findings should be taken into consideration during pharmacotherapy of patients with AII.
Asunto(s)
Obstrucción Intestinal/metabolismo , Hígado/metabolismo , Enfermedad Aguda , Animales , Barbital/farmacología , Biotransformación , Fentanilo/farmacología , Masculino , Meprobamato/farmacología , RatasRESUMEN
Duration of hexenal sleep and activity of main microsomal enzymes in hepatocytes were studied in experimental osteomyelitis of rat mandible. Within 7, 10 and 14 days after the osteomyelitis development content of cytochromes P-450 and b5 as well as activities of amidopyrine N-demethylase, aniline hydroxylase and NADPH cytochrome c reductase were decreased in liver cell microsomal fraction. As liver tissue monooxygenase enzymatic system is inhibited in osteomyelitis the elevated pharmacological activity and toxicity of drugs, metabolized in liver tissue, should be considered under conditions of practical use of these drugs.
Asunto(s)
Enfermedades Mandibulares/metabolismo , Microsomas Hepáticos/enzimología , Osteomielitis/metabolismo , Enfermedad Aguda , Animales , Biotransformación , Hexobarbital/farmacología , Masculino , Enfermedades Mandibulares/enzimología , Microsomas Hepáticos/metabolismo , Osteomielitis/enzimología , Oxidación-Reducción , Ratas , Sueño/efectos de los fármacosAsunto(s)
Quemaduras/metabolismo , Hígado/metabolismo , Preparaciones Farmacéuticas/metabolismo , Analgesia , Animales , Biotransformación/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Masculino , Tono Muscular/efectos de los fármacos , Ratas , Convulsiones/inducido químicamente , Sueño/efectos de los fármacos , Factores de TiempoRESUMEN
In acute rat kidney insufficiency, caused by bilateral nephrectomy or ureter ligation, functional activity of hepatocyte cytoplasmic structure was decreased. Estimation of the cytoplasmic structures functional state included studies of hexenal anesthesia duration, determination of cytochromes P-450 and b5 content in liver microsomal fraction as well as of activities of amidopyrine-N-demethylase and aniline hydroxylase. The alterations of these parameters occurred apparently due to the effect of high concentrations of urea on liver tissue.
Asunto(s)
Lesión Renal Aguda/metabolismo , Hígado/metabolismo , Lesión Renal Aguda/patología , Aminopirina N-Demetilasa/metabolismo , Anilina Hidroxilasa/metabolismo , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Grupo Citocromo b/metabolismo , Citocromos b5 , Citoplasma/fisiología , Hígado/patología , Masculino , Microsomas Hepáticos/metabolismo , Nefrectomía , Ratas , Urea/metabolismoRESUMEN
The effects of hexachlorocyclohexane (HCHCH) on the weight of the liver, content of protein, glycogen, total lipids as well as morphological and ultrastructural changes in the liver were studied. It was established that HCHCH caused a considerable increase in the weight of the liver, as well as in the levels of protein, glycogen and total lipids, which was particularly pronounced following prolonged administration of HCHCH in the dose 1/50 LD50. Large doses of HCHCH (1/3 LD50) brought about marked dystrophic changes in the liver similar to the type of hydropic degeneration, accumulation of fatty drops in hepatocytes Application of a dose 1/50 LD50 of HCHCH resulted in an increased size of hepatocytes, dystrophic changes being noted only in individual cells. Histochemisally there were revealed high levels of RNA and glycogen in hepatocytes. An-Electron-microscopy study of hepatic cells showed the most manifested changes in the endoplasmatic network of hepatocytes, which were seen in an enlargement of the elements of the smooth endoplasmatic reticulum. A suggestion was put forward that the changes indicated above were associated with a stimulating effect of HCHCH on the microsomic system of hepatocytes, i.e. on the enzymatic systems localized in the smooth endoplasmatic network.