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Andrographolide, an Antioxidant, Counteracts Paraquat- Induced Mutagenesis in Mammalian Cells
Authors
John M. Essigmann
Bogdan I Fedeles
+4 more
Nuchanart Rangkadilok
Jutamaad Satayavivad
Tawit Suriyo
Preechaya Tajai
Publication date
27 August 2021
Publisher
EpiSmart Science Vector Ltd
Doi
Abstract
© This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License. Paraquat (1,1’-dimethyl, 4,4’-bipyridinium dichloride; PQ), a commonly used herbicide worldwide, is both toxic and mutagenic. The mutagenic effect of PQ stems from its ability to redox-cycle, generating oxidative stress and subsequently oxidative DNA damage, which miscodes when replication is attempted. Andrographolide (AP1), the major constituent in the leaves of the herbaceous plant Andrographis paniculata, is a diterpenoid with reported antioxidant activity. The present study employed the mammalian cell line AS52 to investigate the protective effect of AP1 against PQ-induced mutagenesis. AP1 induced cytotoxicity in AS52 cells in a dose-dependent manner (IC50 = 15.7 µM), which allowed the selection of a non-lethal dose for the mutagenesis studies. While PQ was mutagenic in AS52 cells as evidenced by the increased levels of 6-TGr mutants, AP1 by itself did not increase the mutation frequency. However, co-treatment with AP1 (1-5 µM) or the antioxidant N-acetylcysteine (2 mM) almost completely counteracted the mutagenicity of PQ (10-100 µM) in AS52 cells. Taken together, these findings suggest that AP1, and likely by extension, A. paniculata extracts, are effective antioxidants that can protect against PQ-induced mutations, and thus could be a promising alternative treatment for PQ poisoning.National Institutes of Health (Grants P30-ES002109, R01-CA080024 and P01- CA26731
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Last time updated on 19/10/2021