Gatifloxacin-induced histamine release and hyperglycemia in rats

Gatifloxacin, a fluoroquinolone antimicrobial agent, has been reported to cause both hypoglycemia and hyperglycemia in diabetic and non-diabetic patients. The purpose of the present study was to investigate the mechanism of gatifloxacin-induced hyperglycemia in normal and diabetic rats. Rats received a single intravenous injection of gatifloxacin and samples of their arterial blood were collected periodically. Diabetic rats were produced by the injection of streptozotocin and nicotinamide. In normal rats, the concentration of serum glucose decreased after the injection of gatifloxacin at 50 mg/kg, while it increased with gatifloxacin at 100 mg/kg. The concentrations of serum epinephrine and histamine increased after the injection of gatifloxacin at 100 mg/kg. The increases in serum glucose and epinephrine concentrations were reduced by pretreatment with diphenhydramine at 1 mg/kg. In diabetic rats, the concentration of serum glucose actually increased after the injection of gatifloxacin at 50 mg/kg, concomitant with increases in the serum epinephrine and histamine concentrations. The concentration of serum immunoreactive insulin slightly increased after the injection of gatifloxacin at 50 mg/kg. In addition, repeated oral administration of gatifloxacin to rats at 300 mg/kg twice a day for 7 days did not change glucose tolerance. In conclusion, gatifloxacin-induced release of histamine can contribute to an increase in the serum epinephrine concentration and hyperglycemia in normal rats. In diabetic rats, lower doses of gatifloxacin can induce hyperglycemia owing to the low level of insulin secretion that they exhibit compared with normal animals.