Abstract
The ototoxic side effects of furosemide on the cochlea, liver and kidney were studied in albino guinea pigs. The amount of 14CO2 oxidized from [1-14C] glucose was measured in vitro with a scintillation counter to investigate the influence of furosemide on glycolysis. Although the inhibitory effect of furosemide on glucose oxidation was seen in each organ, it was especially prominent in the cochlea.
In order to determine the sites of inhibition of this metabolic process, the activity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was estimated by the histochemical method of Himmelhoch. Furosemide or saline was injected into the neck veins of guinea pigs in a concentration of 80mg/kg in 30 seconds under pentobarbital anesthesia. Animals were decapitated at 2, 10, 30 and 60min after furosemide injection. The enzyme activity in each organ was equally inhibited, maximally at 2min, by the administration of furosemide. However, it returned to normal most rapidly in the liver.
In conclusion, it is most likely that inhibition of glucose oxidation, especially at the step of GAPDH, is involved in the common mechanism of the oto-and nephrotoxicities of furosemide.
