RESUMEN
The effects of some phenothiazines (promethazine, PMZ; chlorpromazine, CPZ; levomepromazine, LVPZ; thioridazine, TRDZ; trifluoperazine, TFPZ) on the activation and viability of rat peritoneal macrophages were investigated. The macrophage activation was estimated by measuring of luminol-dependent chemiluminescence, induced by phorbol-12-myristate-13-acetate (PMA) (a protein kinase C activator) or calcium ionophore A23187. The viability of macrophages was determined using ATP bioluminescence as a criterion of cell viability. It was observed that all drugs, in concentrations higher than 1 micromol/L, markedly decreased the chemiluminescent index of PMA-activated or A23187-activated macrophages. The inhibitory effect was dose-dependent. It was better expressed in the case of CPZ, followed by TFPZ and TRDZ, and less expressed in the case of PMZ and LVPZ. The suppression of chemiluminescence of PMA-/A23187-activated macrophages by phenothiazines was not a result of their cytotoxic effect. Moreover, it was found that all drugs dose-dependently enhanced the viability of macrophages, estimated by ATP production. The inhibitory effects of phenothiazines on the chemiluminescence of PMA-/A23187-activated macrophages were greater than their ability to decrease KO2-induced chemiluminescence as a result of interaction with superoxide radicals. It may be supposed that the inhibitory effect of phenothiazines on PMA-/A23187-induced chemiluminescence of macrophages is a result not only of interaction between drugs and superoxide radicals, generated during the "oxidative burst" of activated cells. Presumably the drugs have an immunomodulating effect on rat peritoneal macrophages.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Calcio/metabolismo , Activación de Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Fenotiazinas/farmacología , Proteína Quinasa C/metabolismo , Adyuvantes Inmunológicos/química , Animales , Calcimicina/farmacología , Supervivencia Celular/efectos de los fármacos , Activadores de Enzimas/farmacología , Técnicas In Vitro , Activación de Macrófagos/inmunología , Macrófagos Peritoneales/enzimología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Masculino , Estructura Molecular , Fenotiazinas/química , Ratas , Ratas WistarRESUMEN
The influenza virus infection (A/Aichi/2/68) was associated with development of oxidative stress in lung and blood of mice, accompanied by an increase in levels of lipid peroxidation products (conjugated dienes and total malondialdehyde) and a decrease in endogenous amounts of natural antioxidant vitamin E. These effects were most pronounced on the 5th day after virus inoculation, in comparison with those on the 7th. Supplementation of mice with exogenous vitamin E before virus inoculation lead to lung and blood protection against lipid peroxidation. A marked decrease in lipid peroxidation products and an increase in vitamin E content was established in blood and lung on the 5th and 7th day after virus inoculation. The stabilizing effect of vitamin E is dose-dependent in blood and dose-independent in lung, and was most pronounced on the 5th day after virus inoculation in comparison with the 7th day.
Asunto(s)
Antioxidantes/farmacología , Virus de la Influenza A , Peroxidación de Lípido/efectos de los fármacos , Infecciones por Orthomyxoviridae/metabolismo , Vitamina E/farmacología , Animales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Pulmón/metabolismo , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos ICR , Estrés Oxidativo/efectos de los fármacos , Factores de Tiempo , Vitamina E/sangre , Vitamina E/metabolismoRESUMEN
Influenza virus infection was associated with development of oxidative stress in liver of mice, viz. increase in amount of lipid peroxidation products, decrease in cytochrome P-450 and NADP. H-cytochrome c-reductase activity, and inhibition of liver monooxygenases (aniline hydroxylase, ethylmorphine-N-demethylase, amidopyrine-N-demethylase and analgin-N-demethylase). These effects were most pronounced on the 7th day after virus inoculation as compared to the 5th one. Supplementation of mice with vitamin E before virus inoculation leads to liver protection against oxidative stress and toxicosis. A marked decrease of lipid peroxidation products and an increase of cytochrome P-450 and activities of monooxygenases was established. The stabilizing effect of vitamin E was dose-dependent and was most pronounced on the 5th day after virus inoculation as compared to the 7th one.