RESUMEN
Corneae of guinea pigs were burned with 200 microliters 1N-NaOH for 30 seconds. Topical application of 1%, 0.1%, or 0.025% indomethacin (IN) four times daily resulted in a marked delay of corneal re-epithelialization compared to corneae receiving the vehicle only. However, no retardation of corneal wound healing was observed when IN was injected intraperitoneally (5 mg/kg) twice daily, but hyperemia and chemosis were reduced. To study the proportion of retained IN in burned cornea, 0.1% IN was mixed with a tracer dose of [2-14C] IN: 3.4, 1.2, 0.42, and 0.24% of the dose were retained 20, 60, 180, and 360 minutes respectively after topical application of 15 microliters. Twenty minutes after application of 15 microliter 0.1% IN, the concentration of retained IN in the cornea was 31 micrograms/g, which is considerably higher than the average concentration of 0.358 microgram/ml found in human blood plasma after therapeutic doses of IN. Thus, the retardation of corneal wound healing may be explained by a cytotoxic effect of supratherapeutic concentrations of IN.
Asunto(s)
Quemaduras Químicas/tratamiento farmacológico , Lesiones de la Cornea , Quemaduras Oculares/tratamiento farmacológico , Indometacina/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Administración Tópica , Álcalis , Animales , Quemaduras Químicas/metabolismo , Córnea/metabolismo , Relación Dosis-Respuesta a Droga , Quemaduras Oculares/metabolismo , Cobayas , Indometacina/metabolismo , Masculino , Factores de TiempoRESUMEN
The mechanism of the increase of phosphatidylcholine in liver, accompanying enzyme induction by phenobarbital, has been studied in rats. Using radioactively labeled precursors, the two main pathways of phosphatidylcholine biosynthesis--the CDP-choline pathway and the methylation of phosphatidylethanolamine--were analyzed after pretreatment with 4 doses of phenobarbital (80 mg/kg) on 3 consecutive days. After i.v. injection of choline [Me-3H], choline [Me-14C] or NaH2[32P]O4 the specific radioactivity (sp. act.) of phosphatidylcholine (dpm/nmol) was decreased by 60%, and after methionine [Me-3H] or ethanolamine [1.2-14C] by 40% compared to control rats. These changes are partly due to the increased concentration of phosphatidylcholine and phosphatidylethanolamine, causing the incorporated precursors to dilute, and partly to a secondary effect which leads to a reduction of the sp. act. of free choline in pretreated animals. The concentration of glycerylphosphorylcholine, one of the metabolites of phosphatidylcholine catabolism, was also diminished by almost 50%. From these results it may be concluded that the increase of phosphatidylcholine is due to a retardation of its breakdown rather than to an increase of its synthesis.
