Functional and Morphological Characteristics of Pancreatic Islet Lesions Induced by Quinolone Antimicrobial Agent Gatifloxacin in Rats

Abstract

We characterized pancreatic islet lesions induced by several quinolones using functional and morphological examinations of the pancreatic islets in male rats orally administered gatifloxacin, lomefloxacin, or levofloxacin at 300 mg/kg for 14 consecutive days. Consequently, in contrast to lomefloxacin or levofloxacin, gatifloxacin increased serum glucose and glycosylated albumin on day 14 and elevated serum glucose tended to decrease insulin in the intravenous glucose tolerance test. Microscopically, only gatifloxacin induced cytoplasmic vacuoles containing eosinophilic homogenous contents in islet cells. Immunohistochemical examination revealed that vacuolated islet cells were positively stained for insulin, demonstrating they were pancreatic b cells. Electron microscopy showed that the cytoplasmic vacuoles represented dilated cisterna of the rough endoplasmic reticulum filled with electron-lucent materials in pancreatic b cells. Moreover, insulin secretory granules were drastically decreased in vacuolated islet cells, suggesting impaired insulin synthesis and/or transport. This gatifloxacin-induced pancreatic toxicity in rats was considered to be associated with high pancreatic drug distribution. These results demonstrated that gatifloxacin provoked functional and morphological pancreatic b cell alteration associated with impaired insulin synthesis and/or transport, leading to hyperglycemia.

Insulinotropic Potential of Moxifloxacin and Gemifloxacin: An In Vivo Rabbits Model Study Followed by Randomized Phase I Clinical Trial

“…However, regarding Moxifloxacin and Gemifloxacin , this mechanism is yet to be explored. However, it is clear that Moxifloxacin and Gemifloxacin caused insulin surges that produced blood glucose lowering effects, although there are reports that that hypoglycemic effect of fluoroquinolones is due to activation of ATP sensitive K channels in pancreatic beta cells [ 25 , 26 ]. Additionally, we translated that Moxifloxacin and Gemifloxacin produced a fall in blood glucose levels.…”

Polish Journal of Veterinary Sciences

“…Intoxication as a reason for smaller islets in cPSS dogs should be considered, as such patients show permanent hyperammonemia. Furthermore, in 5 of 43 dogs we found eosinophilic masses in pancreatic islets, and homogenous eosinophilic contents in islet cells have been seen in rats during gatifloxacin intoxication (Yabe et al 2019). Furthermore, a connective tissue hyperplasia found in pancreatic islets of 4 cPSS dogs could result from the toxic effect, as some chronic intoxications have been shown to produce such lesions in other organs (Cui et al 2011, Zhang et al 2018.…”

“…This condition is associated with hypoinsulinemia and hyperglycemia, whereas cPSS dogs are more likely to exhibit the opposite pattern of laboratory abnormalities (Collings et al 2012). Reduced size of pancreatic islets has also been seen in several intoxications in experimental animals (Kikumoto et al 2010, Yabe et al 2019. Intoxication as a reason for smaller islets in cPSS dogs should be considered, as such patients show permanent hyperammonemia.…”

Polish Journal of Veterinary Sciences

“…Intoxication as a reason for smaller islets in cPSS dogs should be considered, as such patients show permanent hyperammonemia. Furthermore, in 5 of 43 dogs we found eosinophilic masses in pancreatic islets, and homogenous eosinophilic contents in islet cells have been seen in rats during gatifloxacin intoxication (Yabe et al 2019). Furthermore, a connective tissue hyperplasia found in pancreatic islets of 4 cPSS dogs could result from the toxic effect, as some chronic intoxications have been shown to produce such lesions in other organs (Cui et al 2011, Zhang et al 2018.…”

“…This condition is associated with hypoinsulinemia and hyperglycemia, whereas cPSS dogs are more likely to exhibit the opposite pattern of laboratory abnormalities (Collings et al 2012). Reduced size of pancreatic islets has also been seen in several intoxications in experimental animals (Kikumoto et al 2010, Yabe et al 2019. Intoxication as a reason for smaller islets in cPSS dogs should be considered, as such patients show permanent hyperammonemia.…”