Evaluation of Cinnamaldehyde toxicity under subacute treatment in a murine experimental model

Abstract

Cinnamaldehyde (Cinn) is the aldehyde responsible for giving cinnamon its characteristic flavor and aroma, and it is one of its main constituents. This compound is used in beverages, repellents, insecticides, dental products, and flavoring agents. The main objective of this study was to investigate the subacute toxicity effects of Cinn (2000 mg/kg/day) administered intrarectally for 15 consecutive days in adult male C57BL/6 mice.

The mice were evaluated daily for clinical status (morbidity or mortality) and behavior. The neurotoxic potential and physiological parameters of Cinn were assessed using a Functional Observational Battery (FOB) and spontaneous locomotor activity. Additionally, sperm motility, liver function, macroscopic and microscopic liver morphology, and relative liver weight were evaluated. Food and water intake were also monitored to support the previously evaluated parameters. All studies were approved by the Institutional Committee for Care and Use of Laboratory Animals (CICUAL), resolution number PV-2020-00212339-UNC-SCT#FCM.

The subacute toxicity results showed no mortality in this in vivo study with rectal dosing. No evidence of neurotoxicity was observed in the FOB or locomotor activity with Cinn. The other parameters, such as food and water intake, liver function tests, liver histopathology, and sperm motility, remained within normal limits. The only significant findings were a reduction in body weight (-0.95 ± 0.46 g; p = 0.0028) in the Cinn-treated animals, along with an increase in relative liver weight (5.98 ± 0.08 g; p = 0.0227). Additionally, signs of local irritation in the perianal region (eczema, perilesional alopecia, and excoriations due to scratching) were noted, which were associated with the direct action of Cinn on the skin.

In conclusion, based on the preliminary observations presented here, we suggest that there is no relevant toxicity risk with subacute intrarectal administration of Cinn. Finally, the intrarectal route could serve as an alternative method of administration for Cinn, and this methodology could be employed to assess the toxicity of active ingredients obtained from plants, which are commonly used in medical applications