Journal
BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY
Volume 101, Issue 2, Pages 125-134Publisher
WILEY
DOI: 10.1002/bdrb.21092
Keywords
4-O-methylhonokiol; nicotine; anti-inflammation; antiapoptosis; dysmorphology; antioxidant
Categories
Funding
- Priority Research Centers Program [2011-0031403]
- Basic Science Research Program [2013016519]
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BACKGROUND Since the increasing smoking rate among women has resulted in higher rates of embryonic malformations, it is important to search for an efficient and inexpensive agent that can help reduce the rate of serious fetal anomalies caused by maternal cigarette smoking. In this study, the bioavailability of 4-O-methylhonokiol isolated from Magnolia officinalis was first demonstrated in the mouse embryos exposed to nicotine using a whole embryo culture system. METHODS Mouse embryos on embryonic day 8.5 were cultured with 1 mM nicotine and/or 4-O-methylhonokiol (1 x 10(-4) or 1 x 10(-3)mu M) for 48hr and were analyzed on the viewpoints of embryo developmental changes, oxidative damages, and apoptotic and inflammatory changes. RESULTS Embryos exposed to 1 mM nicotine developed not only severe morphological anomalies, increased expressions of tumor necrosis factor-alpha, interleukin-1 beta, and caspase 3 mRNAs; and elevated levels of lipid peroxidation, but also decreased levels of cytoplasmic superoxide dismutase, cytosolic glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, hypoxia inducible factor-1 alpha, and B-cell lymphoma-extra large mRNAs, and reduced superoxide dismutase activity. However, these parameters were significantly improved when embryos exposed to the nicotine were concurrently treated with 4-O-methylhonokiol (1 x 10(-4) or 1 x 10(-3)mu M). CONCLUSIONS These findings indicate that 4-O-methylhonokiol reduces serious embryo anomalies caused by nicotine in mouse embryos via the modulations of oxidative stress, apoptosis, and inflammation, suggesting that 4-O-methylhonokiol may be a preventive and therapeutic agent against the dysmorphology induced by maternal smoking during pregnancy.
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