The influence of anesthetic concentrations of enflurane and ethanol on caffeine metabolism in mice

Enflurane is a fluorinated volatile anesthetic, mostly eliminated unchanged in exhaled air. About 10 % of inhaled enflurane undergoes oxidative metabo lism in liver via mixed function oxidase. We examined the influence of etha nol and subchronical exposition (6 hours a day, during five consecutive day s) to subanesthetic and anesthetic concentrations of enflurane on liver fun ction in BALB/c mice. Specially designed chamber for inhalatory application of anesthetics was constructed for this study. Animals were divided in six groups of twenty. The ethanol treated group was injected with ethanol intr aperitoneally (1 g/kg). Two enflurane treated groups were intraperitoneally injected with 0.9 % solution of sodium chloride (10 ml/kg) and one of them exposed to subanesthetic (0.5 Vol%) and the other one to anesthetic (2.75 Vol%) concentrations of enflurane. Following tare groups received ethanol ( 1 g/kg) and each of them inhaled enflurane at previously mentioned doses. T he control group was intraperitoneally injected with 0.9 % solution of sodi um chloride (10 ml/kg) and did not receive any anesthetic. On the day follo wing the last day of exposure half of the animals from each group were sacr ificed for determination of glucose levels, erythrocyte glutathion levels, haematocrit, alanine aminotransferase (ALT), aspartate aminotransferase (AS T), lactate dehydrogenase (LDH), liver protein and glutathion levels, and t otal cytochrome P-450 (CYP P-450). The other half of animals from each grou p were injected intraperitoneally with caffeine (20 mg/kg). Caffeine and it s metabolites in 8 hour urine were analyzed by high performance liquid chro matography (HPLC) method. Excretion of caffeine and its metabolites was dif ferent among the groups. We followed two caffeine metabolic ratios - 1,3-di methyl uric acid and 3,7-xanthine (1,3-U/3,7-X) and 3,7-dimethyl xanthine 7-xanthine and l-xanthine + 1,7-dimethyl uric acid (3,7-X + 7-X/1-X + 1,7- U). The difference in caffeine metabolites ratios suggests that enflurane c hanges oxidative metabolism in liver via certain subtypes of mixed function oxidase, probably via CYP-4502E1. This effect is more expressed when ethan ol and enflurane are applied together. Ethanol is well known inductor of CY P-4502E1 and the registrated enzyme induction could be explained by both in fluences - of ethanol and enflurane.