Embryopathic effects of thalidomide and its hydrolysis products in rabbit embryo culture: evidence for a prostaglandin H synthase (PHS)‐dependent, reactive oxygen species (ROS)‐mediated mechanism

Lee, Crystal J. J.; Gonçalves, Leônor; Wells, Peter G.

doi:10.1096/fj.10-178814

Cited by 38 publications

(21 citation statements)

References 71 publications

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“…This is plausible only if the mechanism of thalidomide actions is fully understood. Recent works suggest that thalidomide causes limb defects by inducing oxidative stress and apoptosis and inhibiting angiogenesis89101112.…”

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confidence: 99%

Nitric oxide rescues thalidomide mediated teratogenicity

Siamwala

Veeriah

Priya

et al. 2012

Sci Rep

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Thalidomide, a sedative drug given to pregnant women, unfortunately caused limb deformities in thousands of babies. Recently the drug was revived because of its therapeutic potential; however the search is still ongoing for an antidote against thalidomide induced limb deformities. In the current study we found that nitric oxide (NO) rescues thalidomide affected chick (Gallus gallus) and zebrafish (Danio rerio) embryos. This study confirms that NO reduced the number of thalidomide mediated limb deformities by 94% and 80% in chick and zebrafish embryos respectively. NO prevents limb deformities by promoting angiogenesis, reducing oxidative stress and inactivating caspase-3 dependent apoptosis. We conclude that NO secures angiogenesis in the thalidomide treated embryos to protect them from deformities.

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confidence: 99%

Nitric oxide rescues thalidomide mediated teratogenicity

Siamwala

Veeriah

Priya

et al. 2012

Sci Rep

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“…The concentration of TM in the culture medium was 117 μM (30.2 μg/mL) (Lee et al. ) and the Cmax value of the TM concentration in plasma after dosing at 300 mg/kg, a teratogenic dose in Kbl:JW rabbits, was 17.7 μg/mL in pregnant rabbits on GD 9 (Kawamura et al. ).…”

Section: Discussionmentioning

confidence: 99%

Effects of thalidomide on Fgf8, Bmp4 and Hoxa11 expression in the limb bud in Kbl:JW rabbit embryos

Kawamura

Yamashita

Yamauchi

et al. 2014

Congenital Anomalies

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Thalidomide (TM) induces limb defects inhumans and some animal species including rabbits. Although the mechanism of TM-induced limb defects has been investigated for a long period, the limb development-related genes expressions have not been vigorously characterized in rabbits. In this study, we investigated the Fgf8, Bmp4 and Hoxa11 expressions in TM-treated JW rabbit embryos on gestation days (GDs) 10, 11 and 12 by whole mount in situ hybridization. On GDs 10 and 11, growth retardation of the embryo was induced by TM treatment. The Fgf8 expression lengths on GDs 10 and 11 in the forelimb bud were significantly or tended to be decreased in the TM-treated embryos, which was correlated to the growth retardation and was not considered to be directly relevant to the teratogenic effect of TM in the forelimb. The TM-induced characteristic changes in the expression pattern of Hoxa11 and Bmp4 on GDs 10 and/or 11 were not noted. On GD 12, TM-induced growth retardation was not noted and the Fgf8 and Bmp4 expressions were not changed. On the contrary, Hoxa11 expression was narrowed at the anterior region, which was located on the radial side, and was not changed at the middle and posterior regions in the forelimb bud and in all regions in the hindlimb bud. Because the radius malformations were induced by TM treatment, we concluded the decrease in the Hoxa11 expression was related to the TM-induced limb defects and can be a good marker for early prediction of the teratogenic effect of TM.

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“…leg ending at the knee). ROS have been associated with many negative health outcomes such as teratogenesis (including limb deficiency), carcinogenesis, cardiovascular disease, and neurogenerative diseases …”

Section: Commentmentioning

confidence: 99%