Functional and Morphological Characteristics of Pancreatic Islet Lesions Induced by Quinolone Antimicrobial Agent...

Area of Science:

• Pharmacology
• Toxicology
• Endocrinology

Background:

• Quinolone antibiotics are widely used, but their potential toxic effects on pancreatic islets require further investigation.
• Previous studies have suggested a link between certain quinolones and glucose metabolism disturbances.

Purpose of the Study:

• To investigate the functional and morphological effects of gatifloxacin, lomefloxacin, and levofloxacin on pancreatic islets in male rats.
• To elucidate the mechanism underlying gatifloxacin-induced pancreatic toxicity and hyperglycemia.

Main Methods:

• Male rats were administered gatifloxacin, lomefloxacin, or levofloxacin (300 mg/kg) orally for 14 days.
• Functional assessments included serum glucose, glycosylated albumin, and intravenous glucose tolerance tests.
• Morphological examinations involved light microscopy, immunohistochemistry, and electron microscopy of pancreatic islets.

Main Results:

• Gatifloxacin significantly increased serum glucose and glycosylated albumin, and tended to decrease insulin levels during glucose tolerance tests.
• Microscopic analysis revealed cytoplasmic vacuoles in pancreatic beta cells exclusively in gatifloxacin-treated rats.
• Electron microscopy indicated these vacuoles were dilated rough endoplasmic reticulum cisternae, with reduced insulin secretory granules, suggesting impaired insulin synthesis/transport.

Conclusions:

• Gatifloxacin induces functional and morphological alterations in pancreatic beta cells, leading to hyperglycemia in rats.
• The observed toxicity is linked to impaired insulin synthesis and/or transport, potentially due to high pancreatic drug distribution.
• These findings underscore the pancreatic toxicity associated with gatifloxacin, necessitating careful consideration of its clinical use.