RESUMEN
Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.
Asunto(s)
Prednisolona , Contaminantes Químicos del Agua , Animales , Larva , Prednisona/metabolismo , Prednisona/farmacología , Prednisolona/toxicidad , Prednisolona/metabolismo , Contaminantes Químicos del Agua/toxicidad , Estrés OxidativoRESUMEN
Arthrobacter simplex ATCC 6946 (viable cells) was immobilized in a calcium polygalacturonate gel. The trapped cells were used for repeated batchwise bioconversion of steroids. Reichstein's compound S and hydrocortisone were dehydrogenated introducing a double bond between C1 and C2 of ring A. The products 1-dehydro S and prednisolone, respectively, were identified by high pressure liquid chromatography. Steroid dehydrogenase activity increased in the system when an artificial electron acceptor, such as menadione (vitamin K3) was present in the reaction mixture. An airlift-type reactor was used to bioconvert up to 90% of substrate in 15 min, under optimal conditions. The gel entrapped cell preparations were used for repeated batch bioconversion during 30 days; 69 batch bioconversions for Reichstein's compound S were performed during 15 days of operation of the reactor. The operational stability of the process and the feasibility of repeated batch bioconversions was shown to be comparable to similar processes.
Asunto(s)
Arthrobacter/metabolismo , Cortodoxona/metabolismo , Hidrocortisona/metabolismo , Hidroxiesteroide Deshidrogenasas/metabolismo , Arthrobacter/enzimología , Concentración de Iones de Hidrógeno , Microesferas , Oxígeno/metabolismo , Pectinas , Prednisolona/análisis , Prednisolona/metabolismo , Vitamina K/metabolismoRESUMEN
Six lactating women receiving long-term treatment with prednisolone in doses from 10 to 80 mg/day were studied. Serum and milk samples were assayed for prednisolone and endogenous cortisol by a specific high-performance liquid chromatographic method. The milk and serum concentrations vs time curves for prednisolone were virtually parallel, and the milk concentrations were 5% to 25% of those in serum. The milk/serum concentration ratio increased with increasing serum concentration. At a daily dose of 80 mg prednisolone, the infant would ingest less than 0.1% of that dose; this corresponds to less than 10% of the infant's endogenous cortisol production. Because there is an equilibrium between the concentration of prednisolone in milk and serum, the exposure of the infant is minimized if breast-feeding is avoided during the first 4 hours after the dose. We conclude that from a quantitative point of view the exposure of the infant is minimal, and breast-feeding may be permitted at maternal prednisolone doses of at least 20 mg once or twice daily. At higher doses, exposure may be minimized if nursing is performed greater than 4 hours after the dose.
Asunto(s)
Leche Humana/metabolismo , Prednisolona/metabolismo , Femenino , Humanos , Cinética , Prednisolona/sangre , Factores de TiempoAsunto(s)
Prednisolona/metabolismo , Adulto , Niño , Relación Dosis-Respuesta a Droga , Humanos , Cinética , MasculinoRESUMEN
Plasma prednisolone levels have been measured hourly in children receiving a single dose of oral prednisone. Peak prednisolone levels occurred one to two hours after ingestion; half-life studies gave a mean value of 132 minutes in most children. Some children had marked variability in absorption and metabolism of prednisone. Somatomedin activity and cell-mediated immunity were inhibited by plasma prednisolone values which were achieved by single doses of prednisone of 0.5 mg/kg or higher. Monitoring prednisolone levels may be of value in identifying those children who accumulate excessively high levels on moderate dosage regimens.