Nitric oxide rescues thalidomide mediated teratogenicity

Siamwala, Jamila H.; Veeriah, Vimal; Priya, Mani Krishna; Rajendran, Saranya; Saran, Uttara; Sinha, Swaraj; Nagarajan, Sankari; Thangaraj, Pradeep; Chatterjee, Suvro

doi:10.1038/srep00679

Cited by 49 publications

(50 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Determining the molecular targets and signaling pathways facilitating the cell-specific action will shed light on the mechanisms of action of each of these compounds. Many molecular targets have been suggested but the precise molecular pathways involved in anti-inflammation as well as teratogenesis remain to be elucidated (2,22,23,27,36,37). Irrespective of the underlying mechanisms, our findings demonstrate that Pomalidomide, but not Thalidomide and Lenalidomide, is specific for inflammatory response cells.…”

Section: Discussionmentioning

confidence: 66%

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Mahony¹,

Erskine²,

Niven

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Thalidomide and its analog, Lenalidomide, are in current use clinically for treatment of multiple myeloma, complications of leprosy and cancers. An additional analog, Pomalidomide, has recently been licensed for treatment of multiple myeloma, and is purported to be clinically more potent than either Thalidomide or Lenalidomide. Using a combination of zebrafish and chicken embryos together with in vitro assays we have determined the relative anti-inflammatory activity of each compound. We demonstrate that in vivo embryonic assays Pomalidomide is a significantly more potent anti-inflammatory agent than either Thalidomide or Lenalidomide. We tested the effect of Pomalidomide and Lenalidomide on angiogenesis, teratogenesis, and neurite outgrowth, known detrimental effects of Thalidomide. We found that Pomalidomide, displays a high degree of cell specificity, and has no detectable teratogenic, antiangiogenic or neurotoxic effects at potent anti-inflammatory concentrations. This is in marked contrast to Thalidomide and Lenalidomide, which had detrimental effects on blood vessels, nerves, and embryonic development at anti-inflammatory concentrations. This work has implications for Pomalidomide as a treatment for conditions Thalidomide and Lenalidomide treat currently.

show abstract

Section: Discussionmentioning

confidence: 66%

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Mahony¹,

Erskine²,

Niven

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Chick aortic ring assay was performed as described elsewhere [14]. Briefly, chick aortic arches were cut from the heart under sterile conditions.…”

Section: Methodsmentioning

confidence: 99%

Tipping off endothelial tubes: nitric oxide drives tip cells

et al. 2014

Self Cite

View full text Add to dashboard Cite

Angiogenesis, the formation of new blood vessels from pre-existing vessels, is a complex process that warrants cell migration, proliferation, tip cell formation, ring formation, and finally tube formation. Angiogenesis is initiated by a single leader endothelial cell called “tip cell,” followed by vessel elongation by “stalk cells.” Tip cells are characterized by their long filopodial extensions and expression of vascular endothelial growth factor receptor-2 and endocan. Although nitric oxide (NO) is an important modulator of angiogenesis, its role in angiogenic sprouting and specifically in tip cell formation is poorly understood. The present study tested the role of endothelial nitric oxide synthase (eNOS)/NO/cyclic GMP (cGMP) signaling in tip cell formation. In primary endothelial cell culture, about 40 % of the tip cells showed characteristic sub-cellular localization of eNOS toward the anterior progressive end of the tip cells, and eNOS became phosphorylated at serine 1177. Loss of eNOS suppressed tip cell formation. Live cell NO imaging demonstrated approximately 35 % more NO in tip cells compared with stalk cells. Tip cells showed increased level of cGMP relative to stalk cells. Further, the dissection of NO downstream signaling using pharmacological inhibitors and inducers indicates that NO uses the sGC/cGMP pathway in tip cells to lead angiogenesis. Taken together, the present study confirms that eNOS/NO/cGMP signaling defines the direction of tip cell migration and thereby initiates new blood vessel formation.

show abstract

“…Other studies have also demonstrated that blood vessels are targeted and destroyed by thalidomide (D'Amato et al, 1994; Hallene et al, 2006; Tamilarasan et al, 2006; Siamwala et al, 2012; Vargesson, 2013). These include rodent and rabbit corneal assays where blood vessels induced in response to a FGF soaked bead are destroyed following thalidomide application (D'Amato et al, 1994; Kenyon et al, 1997).…”

Section: Thalidomide Is Antiangiogenicmentioning

confidence: 96%

Thalidomide‐induced teratogenesis: History and mechanisms

Vargesson

2015

Birth Defects Research Pt C

683

557

View full text Add to dashboard Cite

Nearly 60 years ago thalidomide was prescribed to treat morning sickness in pregnant women. What followed was the biggest man‐made medical disaster ever, where over 10,000 children were born with a range of severe and debilitating malformations. Despite this, the drug is now used successfully to treat a range of adult conditions, including multiple myeloma and complications of leprosy. Tragically, a new generation of thalidomide damaged children has been identified in Brazil. Yet, how thalidomide caused its devastating effects in the forming embryo remains unclear. However, studies in the past few years have greatly enhanced our understanding of the molecular mechanisms the drug. This review will look at the history of the drug, and the range and type of damage the drug caused, and outline the mechanisms of action the drug uses including recent molecular advances and new findings. Some of the remaining challenges facing thalidomide biologists are also discussed. Birth Defects Research (Part C) 105:140–156, 2015. © 2015 The Authors Birth Defects Research Part C: Embryo Today: Reviews Published by Wiley Periodicals, Inc.

show abstract

Nitric oxide rescues thalidomide mediated teratogenicity

Cited by 49 publications

References 37 publications

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic in vitro

Tipping off endothelial tubes: nitric oxide drives tip cells

Thalidomide‐induced teratogenesis: History and mechanisms

Contact Info

Product

Resources

About