Nadolol-glibenclamide interaction: relevance to carbohydrate metabolism in hyperglycaemic rats.

In the present study, hyperglycaemia was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Treatment with glibenclamide (GB) in a dose of 0.45 or 0.9 mg/kg significantly decreased plasma glucose level in a dose-related manner. Administration of nadolol (ND) in a dose of 5 or 10 mg/kg did not affect plasma glucose level. Combined administration of ND (10 mg/kg) with GB (0.45 or 0.9 mg/kg) potentiated the hypoglycaemic effect of GB, an effect prominent 4 hours post-treatment. In relevance to the effect of ND and GB interactions towards other aspects of carbohydrate metabolism, co-administration of the two drugs [ND (10 mg/kg) + GB (0.9 mg/kg)] failed to alter the increase in plasma insulin level and the decrease in blood pyruvate and lactate levels induced by GB alone. Concerning liver glycogen, concurrent administration of the two drugs showed a synergistic effect upon its content (257%), while it was 186% for GB treatment, and 179% for ND alone compared to the hyperglycaemic control value. The data revealed that ND potentiates the hypoglycaemic effect of GB, so it is very important to consider this potentiation when the usage of the combined drug regimens is recommended.

Radiation exposure and the effect of piroxicam and diclofenac on mediator release from isolated guinea-pig lung.

The effects of radiation exposure and drug treatment on the immediate type of hypersensitivity reaction were studied. Guinea-pigs were sensitized by s.c. injections of antigen. The animals were killed 3 weeks later and the lungs were perfused through the pulmonary artery. The perfusate was allowed to superfuse a guinea-pig ileum to estimate its total content of mediators. Results revealed that the mere injection of antigen to the perfused lung resulted in the release of spasmogens which caused contraction of the guinea-pig ileum. Analysis of the effluent showed an increase in the amount of PGs (measured biologically) and histamine (measured fluorimetrically) released during challenge. The response of the ileum to the antigen challenge was inhibited by the infusion of diclofenac (20 micrograms.ml-1) or piroxicam (25 micrograms.ml-1). The drugs also inhibited the release of PGs and histamine from the perfused lungs. Exposure of animals to gamma-radiation, before sensitization, caused a reduction in the amount of mediators released during challenge. On the other hand, in nonsensitized animals, a single radiation dose level of 2 Gy caused fluctuation in the amount of PGs and histamine released during challenge throughout the 3 weeks period of the experiment. Diclofenac and piroxicam effectively reduced the amount of mediators released from sensitized perfused lung isolated from both nonirradiated and irradiated animals. This may, at least partly, explain their protective effect against the exaggerated inflammatory response following gamma-irradiation exposure.