Evaluation of the inhalation toxicity of arecoline benzoate aerosol in rats

Abstract

Arecoline is a pharmacologically active alkaloid isolated from Areca catechu. There are no published data available regarding the inhalation toxicity of arecoline in animals.This study aimed to evaluate the inhalation toxicity of arecoline in vitro and in vivo.For this purpose, arecoline benzoate (ABA) salt was prepared to stabilize arecoline in an aerosol. The MTT assay determined the half-maximal inhibitory concentration values of ABA and arecoline in A549 cell proliferation to be 832 and 412 μg/ml, respectively. The toxicity of acute and subacute inhalation in Sprague-Dawley rats was evaluated using the guidelines of the Organization for Economic Cooperation and Development. For acute inhalation, the median lethal concentration value of ABA solvent was >5175 mg/m 3 . After the exposure and during the recovery period, no treatment-related clinical signs were observed. In the 28-Day inhalation toxicity test, daily nose-only exposure to 2510 mg/m 3 aerosol of the ABA solvent contained 75 mg/m 3 ABA for male rats and 375 mg/m 3 ABA for female rats, which caused no observed adverse effects, except for the decreased body weight gain in male rats exposed to 375 mg/m 3 ABA. In this study, the no observed adverse effect level (NOAEL) for the 28-day repeated dose inhalation of ABA aerosol was calculated to be around 13 mg/kg/day for male rats and 68.8 mg/kg/day for female rats, respectively.

Assessment of Areca Nut Bioactivities in Western Diet-Induced Mice NAFLD Model

“…ARE only significantly ameliorated WD-induced high final body weight and liver weight. The body weights of mice were reduced by ARE, which is consistent with previous studies [ 3 , 4 , 5 ]. ANE only significantly ameliorated WD-induced high final body weight ( Figure 2 ), which is consistent with previous studies [ 31 ].…”

“…ARE is one of the main alkaloids in the areca nut and has been reported to inhibit adipogenic differentiation of preadipocytes and induce lipolysis in adipocytes. Animal data showed that arecoline reduced mice’s body weight at low doses without adverse effects [ 3 , 4 , 5 ]. On the other hand, the ARE base has been reported as a carcinogen in the development of cancer, and the safety of ARE remains controversial [ 6 ].…”