Prof. Naphtali Savion

Professor (Emeritus) of Clinical Biochemistry, Department of Human Molecular Genetics and Biochemistry and Goldschleger Eye Research Institute, Sackler Faculty of Medicine

Novel Antioxidant for Treatment of Age-related Degenerative Diseases

We are studying the potential of S-allylmercapto-N-acetylcysteine (ASSNAC) a newly developed derivative of allicin (the active component in garlic) to serve as a treatment for oxidative stress associated degenerative diseases. The research involves cell biology tools and animal models.

 The following specific subjects are studied:

• Demonstrating the capacity of ASSNAC to activate the transcription factor Nrf2 resulting in up-regulation of the antioxidant cellular mechanisms that increases the protective capacity of cells against reactive oxygen species. The research is done using cells in culture and c. elegans nematodes models.
• Testing the potential of ASSNAC to attenuate the clinical manifestations of neurodegenerative diseases, osteoporosis, retinal degenerating diseases and cataract using animal models.

Selected Publications:

• N. Savion, S. Dahamshi, M. Morein, S. Kotev-Emeth.  S-Allylmercapro-N-Acetylcysteine Attenuates the Oxidation-Induced Lens Opacification and Retinal Pigment Epithelial Cell Death In Vitro. Antioxidants, 8:25, 2019. [I.F. 4.520]   10.3390/antiox8010025

• N. Savion, A. Levine, S. Kotev-Emeth, U. Bening Abu-Shach, L. Broday.  S-allylmercapto-N-acetylcysteine protects against oxidative stress and extends lifespan in Caenorhabditis elegans. PLOS One, 13(3):e0194780. 2018.      10.1371/journal.pone.0194780

• Budnik, B. Shenkman, H. Hauschner, I. Zilinsky, N. Savion.  Role of heterotrimeric G proteins in platelet activation and clot formation in platelets treated with integrin αIIbβ3 inhibitor. Platelets, 29(3):265-269, 2017.    (DOI: 10.1080/09537104.2017.1295136)

• D. Ben-Zvi, N. Savion, F. Kolodgie, A. Simon, S. Fisch, K. Schäfer, N. Bachner-Hinenzon, X. Cao, A. Gertler, G. Solomon, E. Kachel, E. Raanani, J. Lavee, S. Kotev Emeth, R. Virmani, F.J. Schoen, J. Schneiderman.  Local application of leptin antagonist attenuates Angiotensin II-induced ascending aortic aneurysm and cardiac remodeling. J. Am. Heart Assoc. 5(5):e003474; 2016.  (doi: 10.1161/JAHA.116.003474).
• Budnik, B. Shenkman, N. Savion.  Role of G protein signaling in formation of the fibrin(ogen)–integrin αIIbβ3–actin cytoskeleton complex in platelets. Platelets, 27(6):563-575, 2016. (DOI: 10.3109/09537104.2016.1147544)
• Budnik, B. Shenkman, N. Savion.  Synergistic effect of signaling from receptors of soluble platelet agonists and outside-in signaling in formation of a stable fibrinogen–integrin αIIbβ3–actin cytoskeleton complex. Thromb. Res. 135:114–120, 2015. (http://dx.doi.org/10.1016/j.thromres.2014.10.005)
• N. Savion, N. Izigov, M. Morein, S. Pri-Chen, S. Kotev-Emeth.  S-Allylmercapto-N-acetylcysteine (ASSNAC) protects cultured nerve cells from oxidative stress and attenuates experimental autoimmune encephalomyelitis. Neurosci. Lett. 583:108-113, 2014. 10.1016/j.neulet.2014.09.034
• I. Ben Aharon, H. Bar Joseph, M. Tzabari, B. Shenkman, N. Farzam, M. Levi, R. Shalgi, S.M. Stemmer, N. Savion. Doxorubicin-induced vascular toxicity - Targeting potential pathways may reduce procoagulant activity. PLOS ONE, 8(9): e75157, 2013.      (doi:10.1371/journal.pone.0075157)
• M. Tao, P. Yu, B.T. Nguyen, B. Mizrahi, N. Savion, G. Sukhova, F.D. Kolodgie, R. Virmani, C.K. Ozaki, J. Schneiderman. Locally Applied Leptin Induces Regional Aortic Wall Degeneration in ApoE Deficient Mice Preceding Aneurysm Formation. Arterioscler. Thromb. Vasc. Biol. 33(2):311-20, 2013. (doi:10.1161/ATVBAHA.112.300543.)
• J. Schneiderman, K. Schaefer, F.D. Kolodgie, N. Savion, S. Kotev-Emeth, R. Dardik, A.J. Simon, M. Halak, C. Pariente, I. Engelberg, S. Konstantinides, R. Virmani. Leptin Locally Synthesized in Carotid Atherosclerotic Plaques may be Associated with Lesion Instability and Cerebral Emboli. J. Am. Heart Assoc. September 4, 2012; 1: e001727.      (doi:10.1161/JAHA.112.001727).
• S. Mendelboum Raviv, K. Szekeres-Csiki, A. Jenei, J. Nagy, B. Shenkman, N. Savion, J. Harsfalvi. Coating conditions matter to collagen matrix formation regarding von Willebrand factor and platelet binding. Thromb. Res. 129: e29–e35, 2012.      (doi:10.1016/j.thromres.2011.09.030)
• N. Izigov, N. Farzam, N. Savion. S-allylmercapto-N-acetylcysteine up-regulates cellular glutathione and protects vascular endothelial cells from oxidative stress. Free Radic. Biol. Med. 50: 1131–1139, 2011. (DOI:10.1016/j.freeradbiomed.2011.01.028)
• L. Horev-Azaria, S, Eliav, N. Izigov, S. Pri-Chen, D. Mirelman, T. Miron, A. Rabinkov, M. Wilchek, J. Jacob-Hirsch, N. Amariglio, N. Savion. Allicin Up-Regulates Cellular Glutathione Level in Vascular Endothelial cells. Eur. J. Nutrition, 48: 67-74, 2009.     (DOI:10.1007/s00394-008-0762-3)
• N. Geffen, M. Topaz, L. Kredy-Farhan, I. Barequet, N. Farzam, E.I. Assia, N. Savion. Phacoemulsification-induced injury in corneal endothelial cells is mediated by apoptosis: a novel in-vitro model. J. Cataract Refract. Surg., 34: 2146-2152, 2008.      (DOI:10.1016/j.jcrs.2008.08.024)
• B. Shenkman, S. Matetzky, P. Fefer, H. Hod, Y. Einav, A. Lubetsky, D. Varon, N. Savion. Variable responsiveness to clopidogrel and aspirin among patients with acute coronary syndrome as assessed by platelet function tests. Thromb. Res., 122: 336-345, 2008.     (DOI:10.1016/j.thromres.2007.10.018)
• S. Pitaru, M. Noff, L. Blok, E. Nir, S. Pitaru, A. Goldlust, N. Savion. Long-term efficacy of a novel ribose-cross-linked collagen dermal filler: A histologic and histomorphometric study in an animal model. Dermatologic Surgery 33(9): 1045-1053: 2007.     (DOI:10.1111/j.1524-4725.2007.33218.x)
• N. Savion, D. Varon. Impact - The Cone and Plate(let) Analyzer: Testing Platelet Function and Anti-Platelet Drug Response. J. Pathophysiol. Haemost. Thromb. 35: 83-88, 2006.     (DOI:10.1159/000093548)
• Y. Porat, S. Porozov, D. Belkin, D. Shimoni, Y. Fisher, A. Belleli, D. Czeiger, W. F. Silverman, M. Belkin, A. Battler, V. Fulga, N. Savion. Isolation of an Adult Blood-Derived Progenitor Cell Population Capable of Differentiation into Angiogenic, Myocardial and Neural Lineages. Brit. J. Haematol. 135: 703-714; 2006. (DOI:10.1111/j.1365-2141.2006.06344.x)
• A. Solpov, B. Shenkman, Y. Vitkovsky, G. Brill, A. Koltakov, N. Farzam, D. Varon, I. Bank, N. Savion. Platelets Enhance CD4+ Lymphocyte Adhesion to Extracellular Matrix under Flow Conditions: Role of Platelet Aggregation, Integrins, and non-Integrin Receptors. Thromb. Haemost. 95: 815-821, 2006.     (DOI:10.1160/TH05-07-0524)
• S. Matetzky, B. Shenkman, V. Guetta, M. Shechter, R. Bienart, I. Goldenberg, I. Novikov, H. Pres, N. Savion, D. Varon, H. Hod. Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction. Circulation 109: 3171-3175, 2004. (DOI:10.1161/01.CIR.0000130846.46168.03)
• S. Kotev-Emeth, S. Pitaru, S. Pri-Chen, N. Savion. Establishment of a rat long-term culture expressing the osteogenic phenotype: dependence on Dexamethasone and FGF-2. Connective Tissue Res, 43: 606-612, 2002.      (DOI:10.1080/03008200290001339)
• N. Savion, B. Shenkman, I. Tamarin, R. Dardik, D. Varon. Transient adhesion refractoriness of platelets under flow conditions: The role of partial activation and microaggregate formation in controlling thrombus expansion. Brit. J. Haematol. 112: 1055-1061, 2001.     (DOI:10.1046/j.1365-2141.2001.02657.x)
• R. Dardik, D. Varon, I. Tamarin, A. Zivelin, O. Salomon, B. Shenkman, N. Savion. Homocysteine and oxidized low density lipoprotein enhance platelet adhesion to endothelial cells under flow conditions: Distinct mechanisms of thrombogenic modulation. Thromb. Haemost. 83:338-344, 2000.
• D. Varon, R. Dardik, B. Shenkman, S. Kotev-Emeth, N. Farzame, I. Tamarin, N. Savion. A new method for quantitative analysis of whole blood platelet interaction with extracellular matrix under flow conditions. Thromb. Res. 85:283-294, 1997.     (DOI:10.1016/S0049-3848(97)00014-5)
• A. Battler, M. Scheinowitz, A. Bor, D. Hasdai, Z. Vered, E. Di Segni, N. Varda-Bloom, D. Nass, S. Engelberg, M. Eldar, M. Belkin, N. Savion. Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium. J. Am. Coll. Cardiol. 22: 2001-2006, 1993.
• S. Pitaru, S. Kotev-Emeth, D. Noff, S. Kaffuler, N. Savion. Effect of basic fibroblast growth factor on the growth and differentiation of adult stromal bone marrow cells: enhanced development of mineralized bone-like tissue in culture. J. Bone Mineral Res. 8: 919-929, 1993.