Toxicological Parameters of a Formulation Containing Cinnamaldehyde for Use in Treatment of Oral Fungal Infections: An In Vivo Study

Biomed Res Int. 2021 Oct 22:2021:2305695. doi: 10.1155/2021/2305695. eCollection 2021.

Abstract

Objective: We aimed to define the safety and toxicity of both isolated and embedded cinnamaldehyde using a pharmaceutical formulation for the treatment of oral fungal infections in an in vivo study.

Materials and methods: Acute toxicity was assessed in studies with Galleria mellonella larvae and Danio rerio embryos (zebrafish), and genotoxicity was assessed in a mouse model. The pharmaceutical formulation (orabase ointment) containing cinnamaldehyde was evaluated for verification of both in vitro antifungal activity and toxicity in keratinized oral rat mucosa.

Results: In Galleria mellonella larvae, cinnamaldehyde was not toxic up to the highest dose tested (20 mg/kg) and presented no genotoxicity up to the dose of 4 mg/kg in the model using mice. However, it was found to be toxic in zebrafish embryos up to a concentration of 0.035 μg/mL; LC50 0.311; EC50 0.097 (egg hatching delay); and 0.105 (Pericardial edema). In the orabase antifungal susceptibility test, cinnamaldehyde exhibited activity in concentrations greater than 200 μg/mL. As for safety in the animal model with rats, the orabase ointment proved to be safe for use on keratinized mucosa up to the maximum concentration tested (700 μg/mL).

Conclusions: At the concentrations tested, cinnamaldehyde was not toxic in vertebrate and invertebrate animal models and did not exhibit genotoxic activity. In addition, when used in the form of an ointment in orabase, having already recognized antifungal activity, it was shown to be safe up to the highest concentration tested.

MeSH terms

  • Acrolein / analogs & derivatives*
  • Acrolein / metabolism
  • Acrolein / pharmacology
  • Acrolein / toxicity
  • Animals
  • Antifungal Agents / pharmacology
  • Carboxymethylcellulose Sodium / analogs & derivatives
  • Carboxymethylcellulose Sodium / pharmacology
  • Larva / drug effects
  • Lethal Dose 50
  • Male
  • Mice / embryology
  • Moths / metabolism
  • Mycoses / drug therapy*
  • Rats
  • Rats, Wistar / embryology
  • Zebrafish / embryology
  • Zebrafish / metabolism

Substances

  • Antifungal Agents
  • Acrolein
  • Orabase
  • Carboxymethylcellulose Sodium
  • cinnamaldehyde