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

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.

Molecular Docking Analysis for Evaluating the Efficacy of Active Components of Essential Oils against Water-Borne Multi-Virulent Bacteria and Virus

“…Furthermore, the antibacterial and antiviral activity of cinnamaldehyde and terpinen-4-ol have also been well documented in the research articles 43,44 . Cinnamaldehyde was found to be not toxic to vertebrates or invertebrates in an in vivo trial conducted by Alves et al 45 . Subash Babu et al 46 found that oral administration of cinnamaldehyde in induced diabetic rats produces a significant antihyperglycemic effect and simultaneously help to reduce total cholesterol and triglyceride levels effect.…”

Fish larvae: an alternative animal model for testing the toxicity of food additives

“…Many studies based on the classification of teratogenic and non-teratogenic substances have demonstrated a high correlation of toxic response between fish and mammals, of over 72%. Therefore, fish embryo and larvae are considered one of the relevant, reliable, controllable and reproducible models for studying the impact that various chemical substances have on the human body (Genest, 2019;Alves et al, 2021). Recently, numerous toxicology studies on fish embryos and larvae have been published, including studies testing the effects of food additives.…”