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Int. J. Mol. Sci. 2012, 13(3), 3988-4002; doi:10.3390/ijms13033988

Dihydrolipoic Acid Induces Cytotoxicity in Mouse Blastocysts through Apoptosis Processes

2 and 1,*
1 Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan 2 Department of Biomedical Engineering and Center for Nano Bioengineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan 3 Department of Physics, Chung Yuan Christian University, Chung Li 32023, Taiwan 4 Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City 252, Taiwan
* Author to whom correspondence should be addressed.
Received: 20 February 2012 / Revised: 15 March 2012 / Accepted: 16 March 2012 / Published: 22 March 2012
(This article belongs to the Section Molecular Toxicology)
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α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 μM DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 μM DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 μM DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 μM do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 μM DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity.
Keywords: dihydrolipoic acid; blastocyst; apoptosis; embryonic development dihydrolipoic acid; blastocyst; apoptosis; embryonic development
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Houng, W.-L.; Lin, C.-A.; Shen, J.-L.; Yeh, H.-I.; Wang, H.-H.; Chang, W.H.; Chan, W.-H. Dihydrolipoic Acid Induces Cytotoxicity in Mouse Blastocysts through Apoptosis Processes. Int. J. Mol. Sci. 2012, 13, 3988-4002.

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