Genotoxicity and toxicological evaluations of Brazilian red propolis oral ingestion in a preclinical rodent model

Jennyfer Andrea Aldana-Mejía; Aline Mayrink de Miranda; Gari Vidal Ccana-Ccapatinta; Luciana Silva de Araújo; Victor Pena Ribeiro; Caroline Arruda; Samuel Nascimento; Iara Squarisi; Tábata Esperandim; Karoline S de Freitas; Saulo D Ozelin; Denise Crispim Tavares; Fernando Silva Ramalho; Jairo Kenupp Bastos

doi:10.1016/j.jep.2022.115920

Genotoxicity and toxicological evaluations of Brazilian red propolis oral ingestion in a preclinical rodent model

J Ethnopharmacol. 2023 Mar 1:303:115920. doi: 10.1016/j.jep.2022.115920. Epub 2022 Nov 11.

Authors

Affiliations

¹ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
² School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
³ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
⁴ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
⁵ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
⁶ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
⁷ Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
⁸ Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
⁹ Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
¹⁰ Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
¹¹ Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
¹² Nucleus of Research in Sciences and Technology, Laboratory of Mutagenesis, University of Franca, Av. Dr. Armando de Sáles Oliveira, 201 - Parque Universitario, Franca, São Paulo, Brazil. Electronic address: [email protected].
¹³ Department of Pathology, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].
¹⁴ School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Avenida do Café, s/nº, Ribeirão Preto, São Paulo, Brazil. Electronic address: [email protected].

PMID: 36372194
DOI: 10.1016/j.jep.2022.115920

Abstract

Ethnopharmacological relevance: Brazilian red propolis is a natural product known due to its medicinal properties. The efficacy of this natural resin has been proved; however, few studies report the safety of its oral use. Some toxic effects of natural products may not be expressed in traditional use, and preclinical studies are necessary to guarantee their safety. Health regulatory agency currently requires these non-clinical studies to develop drugs and herbal medicines, including genotoxic and oral toxicity tests.

Aim of the study: Accomplish the preclinical toxicity studies of Brazilian red propolis extract (BRP) in rodents, including genotoxicity, acute and sub-chronic toxicities.

Material and methods: Genotoxicity assays followed the erythrocyte micronucleus test protocol in a range of 500-2000 mg/kg BRP oral treatment on male Swiss mice. After an up-and-down procedure, acute oral toxicity (single dose) was performed on female Wistar Hannover rats, reaching a 2000 mg/kg BRP oral gavage concentration. Animals were monitored periodically until 14 days and euthanized for a macroscopic necropsy analysis. The sub-chronic oral toxicity test (90 days) was achieved with 1000 mg/kg of BRP on Wistar Hannover rats (males/females). Animals were monitored to evaluated behavioral and biometrical changes, then were euthanized to perfomed hematological, biochemical, and histopathological analyses.

Results: No genotoxic effect of the BRP was detected. The acute toxicity indicated no toxicity of a single oral dose of 2000 mg/kg of BRP. The long-term oral toxicity performed with 1000 mg/kg of BRP altered water and food intake and the biometrics, hematological and biochemical parameters. Biochemical alterations in hepatic and renal parameters were detected only in the males. Despite the detection of biochemical alterations, no histopathological changes were detected in the organs of any group.

Conclusions: BRP, at a higher dose, showed no signs of immediate toxicity. However, the obtained results suggest that the chemical composition and the intake of higher doses deserve special attention regarding possible toxicity.

Keywords: Acute/subchronic toxicity; Brazilian red propolis; Genotoxicity; Oral toxicity; Rats.

MeSH terms

Animals
Brazil
Eating
Female
Male
Mice
Plant Extracts
Propolis* / toxicity
Rats
Rats, Wistar
Rodentia
Toxicity Tests, Acute
Toxicity Tests, Subchronic

Substances

Propolis
Plant Extracts