In vivo genotoxicity of Chios mastic gum in rodent bone marrow micronucleus test

Chios mastic gum (CMG) exhibits several pharmacological activities that have been confirmed by numerous studies. These include antibacterial, anti-inflammatory, hypolipidemic, hypoglycemic, antiatheromatic, and benefits for against gastrointestinal disorders. However, studies focusing on CMG's safety are limited. The aim of the present study is to evaluate the genotoxicity of CMG using the limit test on the mammalian erythrocyte micronucleus assay, in male Wistar rats. CMG was administered by gavage to 5 rats at 2000 mg/kg bw for 3 days, while 5 rats received the vehicle and 5 rats received cyclophosphamide (positive control). Satellite groups of 3 rats were included for the negative control and CMG-treated groups to collect plasma and bone marrow for the chemical analyses. All rats were observed for mortality and clinical signs of toxicity during the dosing period. Rats were euthanatized 20 h after the last treatment, necropsied, and bone marrow was collected for smear preparation. No mortality, clinical signs of toxicity, gross organ pathology, or body weight changes were observed in CMG-treated rats compared to the negative control group. No statistically significant alteration of polychromatic erythrocytes (PCE) and the per-thousand incidences of micronucleated PCE in the bone marrow of CMG-treated rats were observed. Bone marrow exposure to CMG was unambiguously confirmed by the detection of the characteristic CMG triterpenic acids in both bone marrow extract and plasma of CMG-treated rats by UHPLC-HRMS/MS analysis. In conclusion, CMG exhibited no genotoxic effects on bone marrow erythrocytes at the tested limit dose of 2000mg/kg body weight.