Nitric Oxide Rescues Thalidomide Mediated Teratogenicity

Overview

Journal Sci Rep

Specialty Science

Date 2012 Sep 22

PMID 22997553

Citations 23

Authors

Jamila H Siamwala

Vimal Veeriah

M Krishna Priya

Saranya Rajendran

Uttara Saran

Swaraj Sinha

Shunmugam Nagarajan

T Pradeep

Suvro Chatterjee

Affiliations

Soon will be listed here.

Abstract

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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References

Dimmeler S, Haendeler J, Nehls M, Zeiher A . Suppression of apoptosis by nitric oxide via inhibition of interleukin-1beta-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J Exp Med. 1997; 185(4):601-7. PMC: 2196141. DOI: 10.1084/jem.185.4.601. View

Tweedie D, Frankola K, Luo W, Li Y, Greig N . Thalidomide Analogues Suppress Lipopolysaccharide-Induced Synthesis of TNF-α and Nitrite, an Intermediate of Nitric Oxide, in a Cellular Model of Inflammation. Open Biochem J. 2011; 5:37-44. PMC: 3141331. DOI: 10.2174/1874091X01105010037. View

Rafiee P, Stein D, Nelson V, Otterson M, Shaker R, Binion D . Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC). Am J Physiol Gastrointest Liver Physiol. 2009; 298(2):G167-76. PMC: 2822501. DOI: 10.1152/ajpgi.00385.2009. View

Noman A, Koide N, Khuda I, Dagvadorj J, Tumurkhuu G, Naiki Y . Thalidomide inhibits lipopolysaccharide-induced nitric oxide production and prevents lipopolysaccharide-mediated lethality in mice. FEMS Immunol Med Microbiol. 2009; 56(3):204-11. DOI: 10.1111/j.1574-695X.2009.00567.x. View

Murohara T, Asahara T, Silver M, Bauters C, Masuda H, Kalka C . Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J Clin Invest. 1998; 101(11):2567-78. PMC: 508846. DOI: 10.1172/JCI1560. View

Weng W, Sukowati E, Sheng G . On hemangioblasts in chicken. PLoS One. 2007; 2(11):e1228. PMC: 2080762. DOI: 10.1371/journal.pone.0001228. View

Venkatesan B, Mahimainathan L, Das F, Ghosh-Choudhury N, Ghosh Choudhury G . Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells. J Cell Physiol. 2006; 211(2):457-67. DOI: 10.1002/jcp.20953. View

Nath A, Enciso J, Kuniyasu M, Hao X, Madri J, Pinter E . Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy. Development. 2004; 131(10):2485-96. DOI: 10.1242/dev.01131. View

Badamtseren B, Odkhuu E, Koide N, Haque A, Naiki Y, Hashimoto S . Thalidomide inhibits interferon-γ-mediated nitric oxide production in mouse vascular endothelial cells. Cell Immunol. 2011; 270(1):19-24. DOI: 10.1016/j.cellimm.2011.03.018. View

10.

Majumder S, Rajaram M, Muley A, Reddy H, Tamilarasan K, Kolluru G . Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase. Br J Pharmacol. 2009; 158(7):1720-34. PMC: 2801213. DOI: 10.1111/j.1476-5381.2009.00446.x. View

11.

Therapontos C, Erskine L, Gardner E, Figg W, Vargesson N . Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc Natl Acad Sci U S A. 2009; 106(21):8573-8. PMC: 2688998. DOI: 10.1073/pnas.0901505106. View

12.

SHESKIN J . Further observation with thalidomide in lepra reactions. Lepr Rev. 1965; 36(4):183-7. DOI: 10.5935/0305-7518.19650036. View

13.

Gordon J, Goggin P . Thalidomide and its derivatives: emerging from the wilderness. Postgrad Med J. 2003; 79(929):127-32. PMC: 1742651. DOI: 10.1136/pmj.79.929.127. View

14.

DAmato R, Loughnan M, Flynn E, Folkman J . Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A. 1994; 91(9):4082-5. PMC: 43727. DOI: 10.1073/pnas.91.9.4082. View

15.

Hamburger V, HAMILTON H . A series of normal stages in the development of the chick embryo. J Morphol. 2014; 88(1):49-92. View

16.

Kotch L, Chen S, Sulik K . Ethanol-induced teratogenesis: free radical damage as a possible mechanism. Teratology. 1995; 52(3):128-36. DOI: 10.1002/tera.1420520304. View

17.

Cooke J, Losordo D . Nitric oxide and angiogenesis. Circulation. 2002; 105(18):2133-5. DOI: 10.1161/01.cir.0000014928.45119.73. View

18.

Kimmel C, Ballard W, Kimmel S, Ullmann B, Schilling T . Stages of embryonic development of the zebrafish. Dev Dyn. 1995; 203(3):253-310. DOI: 10.1002/aja.1002030302. View

19.

Sampaio E, Sarno E, Galilly R, COHN Z, Kaplan G . Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes. J Exp Med. 1991; 173(3):699-703. PMC: 2118820. DOI: 10.1084/jem.173.3.699. View

20.

Radomski M, Palmer R, Moncada S . The role of nitric oxide and cGMP in platelet adhesion to vascular endothelium. Biochem Biophys Res Commun. 1987; 148(3):1482-9. DOI: 10.1016/s0006-291x(87)80299-1. View