Evaluation of genotoxicity and 13-week subchronic toxicity of root of Asarum heterotropoides var. seoulense (Nakai) Kitag.

Autor: Gu EY; College of Pharmacy, Chung-Nam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: eygu@kitox.re.kr., Jung J; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: jina.jung@kitox.re.kr., Back SM; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: gbsmk@kitox.re.kr., Lim KH; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: khlim@kitox.re.kr., Kim W; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: woojinkim@kitox.re.kr., Min BS; College of Pharmacy, Daegu Catholic University, Gyeongsan, Gyeongbuk, 38430, Republic of Korea. Electronic address: bsmin@cu.ac.kr., Han KH; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: hankh@kitox.re.kr., Kim SK; College of Pharmacy, Chung-Nam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Republic of Korea. Electronic address: sangkim@cnu.ac.kr., Kim YB; Department of Advanced Toxicology Research, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea. Electronic address: ybkim@kitox.re.kr.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2023 Apr 06; Vol. 305, pp. 116012. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1016/j.jep.2022.116012
Abstrakt: Ethnopharmacological Relevance: Asarum heterotropoides var. seoulense (Nakai) Kitag is a traditional herbal medicine used in Korea and China. It is effective in aphthous stomatitis, local anesthesia, headache, toothache, gingivitis, and inflammatory diseases. However, information on the toxicity of the root of Asarum heterotropoides var. seoulense (Nakai) Kitag (AR) is limited. Therefore, preclinical toxicity studies on AR are needed to reduce the risk of excessive intake.
Aim of the Study: We aimed to evaluate genotoxicity and the potential toxicity due to repeated administration of AR powder.
Materials and Methods: In vitro bacterial reverse mutation assay (Ames), in vitro chromosomal aberration assay (CA), and in vivo micronucleus (MN) assay in ICR mice were conducted. As positive results were obtained in Ames and CA assays, alkaline comet assay and pig-a gene mutation test were conducted for confirmation. For evaluating the general toxicity of AR powder, a 13-week subchronic toxicity test was conducted, after determining the dose by performing a single and a 4-week dose range finding (DRF) test. A total of 152 Sprague-Dawley (SD) rats were orally administered AR powder at doses of 0, 150, 350, 500, 1000, and 2000 mg/kg/day in the 13-week subchronic toxicity test. Hematology, clinical chemistry, urinalysis, organ weight, macro-, and microscopic examination were conducted after rat necropsy.
Results: AR powder induced genotoxicity evidenced in the Ames test at 187.5, 750, 375, and 1500 μg/plate of TA100, TA98, TA1537, and E. coli WP2uvrA in the presence and absence of S9, respectively; CA test at 790 μg/mL for 6 h in the presence of S-9; 75 μg/mL for 6 h in the absence of S-9, and 70 μg/mL for 22 h in the absence of S-9 in the stomach in the comet assay but not in MN and pig-a assays. In the 13-week subchronic toxicity study, clinical signs including irregular respiration, noisy respiration, salivation, and decreased body weight or food consumption were observed in males and females in the 2000 mg/kg/day group. In hematology tests, clinical chemistry, urinalysis, organ weight, and macroscopic examination, changes were observed in the dose groups of 500 mg/kg/day and above. Microscopic examination revealed hyperplasia of the stomach as a test-related change. Hepatocellular adenoma and changes in liver-related clinical chemistry parameters were observed. The rat No Observed Adverse Effect Level (NOAEL) was 150 mg/kg/day in males and <150 mg/kg/day in females.
Conclusions: AR powder is potentially toxic to the liver and stomach and should be used with caution in humans. A long-term study on carcinogenicity is necessitated because DNA damage or changes in tissue lesions were observed in SD rats.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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