Hepatic and skeletal muscle mitochondrial toxicity of chitosan oligosaccharides of normal and diabetic rats

Toxicol Mech Methods. 2016 Nov;26(9):650-657. doi: 10.1080/15376516.2016.1222643. Epub 2016 Oct 28.


Diabetes and associated conditions are now considered a worldwide epidemic, with increasing costs and burdens with no cure yet developed. The chitin-derived glucosamine biopolymer chitosan has shown promising results when supplied to diabetic patients. However, no study has investigated the possible toxic side effects of chitosan treatments, in particular when regarding the most important bioenergetic organelle, mitochondria. As such, we aimed to understand if supplementation of chitosan to the diet of normal and diabetic rats could compromise mitochondrial function on two of the major organs involved in diabetes, obesity, and metabolic regulation, the liver and skeletal muscle. We supplemented the drinking water of normal Wistar and diabetic Goto-Kakizaki rats with 0.5% chitosan for 6 weeks. We show here that, in terms of hepatic bioenergetics, chitosan was relatively inert and had no major side effects. However, regarding skeletal muscle bioenergetics, chitosan significantly affected various bioenergetic parameters. As such, we conclude that chitosan, at the tested doses, is relatively safe for treatment of diabetic situations. Nonetheless, the potential for adverse toxicological side effects appears to be present, which might be relevant if higher doses are utilized.

Keywords: Chitosan; chitooligosaccharides; diabetes; mitochondria; toxicity.

MeSH terms

  • Animals
  • Chitosan / toxicity*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Dose-Response Relationship, Drug
  • Energy Metabolism / drug effects
  • Hypoglycemic Agents / toxicity*
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria, Liver / drug effects*
  • Mitochondria, Liver / metabolism
  • Mitochondria, Muscle / drug effects*
  • Mitochondria, Muscle / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Rats, Wistar


  • Hypoglycemic Agents
  • Chitosan