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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Investigation Of Reducing Omniscan Toxicity Using Intracellular And Targeted N-Acetylcysteine Lysine Complex

Author(s): Hadi Hejazinia, Elham Poonaki, Mitra Elmi, Mohammad Esfandiar, Vala Vahedian Boroujeni, Artin Assadi, Seyed Esmaeil Sadat Ebrahimi, Morteza Pirali Hamedani and Mehdi Shafiee Ardestani*

Volume 16, Issue 9, 2019

Page: [1006 - 1019] Pages: 14

DOI: 10.2174/1570180815666180913101717

Price: $65

Abstract

Background: The main issue is finding the most efficient method in the treatment of cancer in terms of early and accurate diagnostic. One of the most modern diagnostic techniques is imaging methods. The accuracy and detection speed of MRI and CT SCAN are high.

Methods: The most important complication of iodinated contrast agents in medical imaging is severe renal toxicity Nephrogenic Systemic Fibrosis (NSF). In order to reduce the cytotoxicity of kidney cells caused by the usage of iodized contrast agents a complex agent should be designed. The two drugs which have been used for the synthesis of this compound are L -lysine amino acid and NAcetyl- Cysteine (NAC).

Results: The synthesis of this complex due to two dimer molecules with each other and NAC greatly a helper for an antioxidant activity and L-lysine amino acid helps in drug entry into the cells. However, helping for an antioxidant activity heavily reinforce and eventually will successfully reduce the cytotoxicity. When its exposure to HEK 293 cell line (P<0.05). The reduction in toxicity at the dosage of 100 µM has been showed as the greatest reduction. The amount of renal toxicity was reported 40% in Omniscan.

Conclusion: Omniscan was tested when iodinated contrast medium was combined with the synthesized 2NAC-LYS-OMNISCAN complex and the human embryonic kidney 293 (HEK293) cell line. Then, the cytotoxicity was reduced to 10 %. On the other hand, the viability increased from 60 % to 90 %, or in other words, the cytotoxicity was reduced from 40 % to 10 %.

Keywords: Cancer, N-acetylcysteine, lysine, NMR, reduced toxicity, increased permeability of omniscan.

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[1]
Yuan, X.; Wu, H.; Xu, H.; Xiong, H.; Chu, Q.; Yu, S.; Wu, G.S.; Wu, K. Notch signaling: An emerging therapeutic target for cancer treatment. Cancer Lett., 2015, 369(1), 20-27.
[2]
Hasebroock, K.M.; Serkova, N.J. Toxicity of MRI and CT contrast agents. Expert Opin. Drug Metab. Toxicol., 2009, 5(4), 403-416.
[3]
Parfrey, P.S.; Griffiths, S.M.; Barrett, B.J.; Paul, M.D.; Genge, M.; Withers, J.; Farid, N.; McManamon, P.J. Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. N. Engl. J. Med., 1989, 320(3), 143-149.
[4]
Coplen, T.B.; Shrestha, Y. Isotope-abundance variations and atomic weights of selected elements: 2016 (IUPAC Technical Report). Pure Appl. Chem., 2016, 88(12), 1203-1224.
[5]
Ding, F.; Zhan, Y.; Lu, X.; Sun, Y. Recent advances in near-infrared II fluorophores for multifunctional biomedical imaging. Chem. Sci., 2018, 9(19), 4370-4380.
[6]
Morcos, K.S. Contrast-Induced nephropathy and nephrogenic systemic fibrosis, an issue of radiologic clinics of North America. Journals of Elsevier, 2009, 47, 5.
[7]
Harpur, E.S.; Worah, D.; Hals, P.A.; Holtz, E.; Furuhama, K.; Nomura, H. Preclinical safety assessment and pharmacokinetics of gadodiamide injection, a new magnetic resonance imaging contrast agent. Invest. Radiol., 1993, 28(Suppl. 1), S28-S43.
[8]
Dean, O.; Giorlando, F.; Berk, M. N-acetylcysteine in psychiatry: Current therapeutic evidence and potential mechanisms of action. J. Psychiatry Neurosci., 2011, 36(2), 78-86.
[9]
Collidge, T.A.; Thomson, P.C.; Mark, P.B.; Traynor, J.P.; Jardine, A.G.; Morris, S.T.; Simpson, K.; Roditi, G.H. Gadolinium-enhanced MR imaging and nephrogenic systemic fibrosis: Retrospective study of a renal replacement therapy cohort. Radiology, 2007, 245(1), 168-175.
[10]
Isidro-Llobet, A.; Alvarez, M.; Albericio, F. Acid-protecting groups. Chem. Rev., 2009, 109(6), 2455-2504.
[11]
Sheehan, J.; Cruickshank, P.; Boshart, G. A convenient synthesis of water-soluble carbodiimides. J. Org. Chem., 1961, 26(7), 2525-2528. [doi:10.1021/jo01351a600].
[12]
Bartczak, D.; Kanaras, A.G. Preparation of peptide-functionalized gold nanoparticles using one pot EDC/Sulfo-NHS Coupling. Langmuir, 2011, 27(16), 10119-10123.
[13]
Schneider, H.J.; Buchheit, U.; Becker, N.; Schmidt, G.; Siehl, U. Proton NMR analyses, shielding mechanisms, coupling constants, and conformations in steroids bearing halogen, hydroxy, and oxo groups and double bonds. J. Am. Chem. Soc., 1985, 107(24), 7027-7039.
[14]
Phelan, K.; May, M.K. Basic techniques in mammalian cell tissue culture. Curr. Protoc. Cell Biol., 2015, 66(1), 1-22. [doi.org/10.1002/0471143030.cb0101s66.].
[15]
Michalet, X.; Pinaud, F.F.; Bentolila, L.A.; Tsay, J.M.; Doose, S.; Li, J.J.; Sundaresan, G.; Wu, A.M.; Gambhir, S.S.; Weiss, S. Quantum dots for live cells, in vivo imaging, and diagnostics. Science, 2005, 307(5709), 538-544.
[16]
van Meerloo, J.; Kaspers, G.J.; Cloos, J. Cell sensitivity assays: The MTT assay. Methods Mol. Biol., 2011, 731, 237-245.
[17]
Girouard, H.; Chulak, C.; Wu, L.; Lejossec, M.; de Champlain, J. N-acetylcysteine improves nitric oxide and α-adrenergic pathways in mesenteric beds of spontaneously hypertensive rats. Am. J. Hypertens., 2003, 16(7), 577-584.
[18]
Shiraishi, K.; Kawano, K.; Minowa, T.; Maitani, Y.; Yokoyama, M. Preparation and in vivo imaging of PEG-poly(L-lysine)-based polymeric micelle MRI contrast agents. J. Control. Release, 2009, 136(1), 14-20.
[19]
Connes, J.; Pierre, C. Near-infrared planetary spectra by fourier spectroscopy I instruments and results. ‎. J. Opt. Soc. Am., 1966, 56(7), 896-910.
[20]
Gillissen, A.; Nowak, D. Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy. Respir. Med., 1998, 92(4), 609-623.
[21]
Safirstein, R.; Andrade, L.; Vieira, J.M. Acetylcysteine and nephrotoxic effects of radiographic contrast agents - a new use for an old drug. N. Engl. J. Med., 2000, 343(3), 210-212.
[22]
Lavasanifar, A.; Samuel, J. Kwon, G.S. Poly (ethylene oxide)-block-poly (l-amino acid) micelles for drug delivery. Adv. Drug Deliv. Rev., 2002, 54(2), 169-190.
[23]
Gillissen, A.; Jaworska, M.; Orth, M.; Coffiner, M.; Maes, P.; App, E.M.; Cantin, A.M.; Schultze-Werninghaus, G. Nacystelyn, a novel lysine salt of N-acetylcysteine, to augment cellular antioxidant defence in vitro. Respir. Med., 1997, 91(3), 159-168.
[24]
Dickey, D.T.; Wu, Y.J.; Muldoon, L.L.; Neuwelt, E.A. Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels. J. Pharmacol. Exp. Ther., 2005, 314(3), 1052-1058.

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