Gatifloxacin (Tequin) is a third-generation, broad-spectrum fluoroquinolone antibiotic which entered the world pharmaceutical market in 2000. It is commonly used to treat various gram positive and gram negative bacterial infections. Although the treatment with gatifloxacin was associated with an increased risk of hypoglycemia the effects of this antibiotic on glucose synthesis have not been examined so far. As in addition to liver, kidney is considered as an important source of glucose production in mammals, this investigation was undertaken to study the action of gatifloxacin on glucose synthesis in rabbit kidney-cortex tubules incubated with various gluconeogenic substrates. The data indicate that in kidney-cortex tubules, a high metabolic stability of gatifloxacin applied at 25 - 100 μM concentration was accompanied by a marked accumulation of the drug in the intracellular milieu and a decrease in the rate of glucose formation from pyruvate (by about 20 - 50%, P<0.005). Surprisingly, gatifloxacin did not affect the rate of gluconeogenesis in the presence of either alanine + glycerol + octanoate or aspartate + glycerol + octanoate. Furthermore, at concentrations from 10 up to 100 μM the drug decreased the rate of mitochondrial oxygen consumption under state 3 condition in the presence of pyruvate + malate (by about 20 - 40%, P<0.005) but it did not affect this process in the presence of glutamate + malate. In view of substrate-dependent differential effects of gatifloxacin on renal gluconeogenesis and mitochondrial respiration, it is likely that the inhibitory action of this antibiotic on gluconeogenesis might result from an impairment of mitochondrial pyruvate uptake. This suggestion is additionally supported by similar metabolic effects of alpha-cyano-4-hydroxycinnamate, the well established inhibitor of the mitochondrial pyruvate transporter.

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