TY - JOUR
T1 - Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system
AU - Shih, Yu Tzu
AU - Chen, Po See
AU - Wu, Chi Han
AU - Tseng, Yu Ting
AU - Wu, Yang Chang
AU - Lo, Yi Ching
N1 - Funding Information:
We appreciate the reviewers’ constructive suggestions. This study was supported by Grant NSC 96-2320-B-037-039-MY3 from the National Science Council, Taiwan, and supported in part by Grant DOH99-TD-C-111-002 from the Excellence for Cancer Research Center, Department of Health, Executive Yuan, Taiwan.
PY - 2010/11/30
Y1 - 2010/11/30
N2 - Arecoline, an areca nut alkaloid, has been noted for its potential cognition-enhancing effects in patients with Alzheimer dementia. However, it has been confirmed that areca nut use is associated with oral and pharyngeal cancers. In addition, arecoline is genotoxic and cytotoxic both in vitro and in vivo through oxidative stress-dependent mechanisms. The aim of this study was to investigate whether arecoline would interfere with the antioxidant defense system and induce cytotoxicity in rat primary cortical neurons. Results indicate that arecoline (50-200 μM) induces neuronal cell death, and catalase, NADPH oxidase inhibitors (diphenyleneiodonium chloride and apocynin), and a caspase inhibitor (z-VAD-fmk) can prevent arecoline-induced cell death. Furthermore, arecoline increased reactive oxygen species production and upregulated protein expression and mRNA levels of NADPH oxidase 2, which could be attenuated by catalase and NADPH oxidase inhibitors. Arecoline also attenuated neuronal antioxidant defense by decreasing glutathione (GSH) level and superoxide dismutase activity. In addition, arecoline enhanced the expression of proapoptotic proteins (cytochrome c, Bax, caspase-9, and caspase-3) and attenuated the expression of the antiapoptotic protein Bcl-2. Moreover, NADPH oxidase inhibitors could attenuate the arecoline-induced GSH depletion and reverse arecoline-induced changes in proapoptotic and antiapoptotic proteins. In conclusion, the results indicate that arecoline could induce neuronal apoptotic death by attenuating antioxidant defense and enhancing oxidative stress.
AB - Arecoline, an areca nut alkaloid, has been noted for its potential cognition-enhancing effects in patients with Alzheimer dementia. However, it has been confirmed that areca nut use is associated with oral and pharyngeal cancers. In addition, arecoline is genotoxic and cytotoxic both in vitro and in vivo through oxidative stress-dependent mechanisms. The aim of this study was to investigate whether arecoline would interfere with the antioxidant defense system and induce cytotoxicity in rat primary cortical neurons. Results indicate that arecoline (50-200 μM) induces neuronal cell death, and catalase, NADPH oxidase inhibitors (diphenyleneiodonium chloride and apocynin), and a caspase inhibitor (z-VAD-fmk) can prevent arecoline-induced cell death. Furthermore, arecoline increased reactive oxygen species production and upregulated protein expression and mRNA levels of NADPH oxidase 2, which could be attenuated by catalase and NADPH oxidase inhibitors. Arecoline also attenuated neuronal antioxidant defense by decreasing glutathione (GSH) level and superoxide dismutase activity. In addition, arecoline enhanced the expression of proapoptotic proteins (cytochrome c, Bax, caspase-9, and caspase-3) and attenuated the expression of the antiapoptotic protein Bcl-2. Moreover, NADPH oxidase inhibitors could attenuate the arecoline-induced GSH depletion and reverse arecoline-induced changes in proapoptotic and antiapoptotic proteins. In conclusion, the results indicate that arecoline could induce neuronal apoptotic death by attenuating antioxidant defense and enhancing oxidative stress.
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U2 - 10.1016/j.freeradbiomed.2010.07.017
DO - 10.1016/j.freeradbiomed.2010.07.017
M3 - Article
C2 - 20691257
AN - SCOPUS:77957751263
VL - 49
SP - 1471
EP - 1479
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 10
ER -