Abstract
The conditions for producing phosphatidylcholine liposomes containing lipoic acid and carnosine together were determined. The obtained liposomes are 180–250-nm spherical particles with an efficiency of lipoic acid inclusion of 50–70% (for carnosine, 17–33%). Based on the model of the oxidation of phosphatidylcholine by hydrogen peroxide, an antioxidant effect of carnosine, lipoic acid or lipoic acid with carnosine together was demonstrated; it consisted in inhibition of lipid peroxidation process, which was manifested in a decrease in the formation of lipid peroxidation products that react with thiobarbituric acid. It was established that lipoic acid (5 mM) and carnosine (0.1–10 mM) in liposomes exhibit an antioxidant effect. At the same time, it was demonstrated that the content of the appropriate lipid peroxidation products in liposomes with antioxidants (lipoic acid + carnosine) was 15 times lower than in control liposomes (without antioxidants). The effect of the obtained liposomal drugs on the platelet aggregation induced by arachidonic acid was evaluated. It was found that the liposomal drug containing lipoic acid (1.5 mM) and carnosine (2.1 mM) inhibited platelet aggregation by 50–55% relative to the control (platelets and arachidonic acid), while liposomes without antioxidants and water-soluble forms of carnosine and lipoic acid had almost no effect on platelet aggregation caused by arachidonic acid.
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REFERENCES
E. I. Gusev and V. I. Skvortsova, Cerebral Ischemia (Meditsina, Moscow, 2001) [in Russian].
E. Yu. Solov’eva, O. P. Mironova, O. A. Baranova, et al., Zh. Nevrol. Psikhiatrii im. S. S. Korsakova 108 (6), 34 (2008).
G. P. Biewenga, G. R. Haenen, and A. Bast, Gen. Pharmacol. 29 (3), 315 (1997).
A. Goraca, H. Huk-Kolega, A. Piechota, et al., Pharmacol. Rep. 63 (4), 849 (2011).
W. M. Clark, L. G. Rinker, N. S. Lessov, et al., Stroke 32 (4), 1000 (2001).
H. Deng, X. Zuo, J. Zhang, et al., Mol. Med. Rep. 11 (5), 3659 (2015).
E. I. Saifullina, L. B. Novikova, G. R. Iksanova, and E. M. Kolchina, Klin. Nevrol. 2, 17 (2017).
L. B. Novikova, G. R. Iksanova, E. M. Kolchina, and Sh. N. Galimov, Nevrol. Zh. 11 (3), 42 (2006).
S. Akiba, S. Matsugo, L. Packer, and T. Konishi, Anal. Biochem. 258 (2), 299 (1998).
A. A. Boldyrev, Biochemistry (Moscow) 77 (4), 313 (2012).
Y. I. Shen, P. He, Y. Y. Fan, et al., Free Radic. Biol. Med. 48 (5), 727 (2010). https://doi.org/10.1016/j.freeradbiomed. 2009.12.021
T. N. Fedorova, S. A. Gavrilova, M. P. Morozova, et al., Vopr. Biol. Med. Farmatsevt. Khim. 20 (4), 25 (2017).
A. A. Devyatov, T. N. Fedorova, S. L. Stvolinskii, et al., Bull. Exp. Biol. Med. 163 (2), 195 (2017).
O. M. Lopacheva, A. V. Lopachev, K. N. Kulichenkova et al., Ann. Klin. Eksp. Nevrol. 12 (1), 38 (2018).
D. S. Berezhnoy, S. L. Stvolinsky, A. V. Lopachev, et al., Amino Acids 51 (1), 139 (2019).
T. N. Fedorova, M. S. Belyaev, O. A. Trunova, et al., Biol. Membrany 25 (6), 458 (2008).
J. F. Lenny, R. P. George, A. M. Weiss, et al., Clin. Chim. Acta 123 (3), 221 (1982).
S. L. Stvolinsky, E. R. Bulygina, T. N. Fedorova, et al., Cell. Mol. Neurobiol. 30 (3), 395 (2010).
N. A. Antonova, G. M. Sorokoumova, T. N. Fedorova, et al., Tonkie Khim Tekhnol. 11 (6), 55 (2016).
Z. A. Suslina, M. M. Tanashyan i V. G. Ionova, Ischemic Stroke: Blood, Vascular Wall, Antithrombotic Therapy (Meditsina, Moscow, 2005) [in Rus.
Z. A. Suslina, A. V. Erofeeva, M. M. Tanashyan, and V. G. Ionova, Nevrol. Vestn., Nos. 3–4, 5 (2005).
M. A. Domashenko and M. M. Tanashyan, Russ. Med. Zh. 19 (9), 562 (2011).
Y. S. Lai, C. Y. Shih, Y. F. Huang, and T. C. Chou, J. Agric. Food Chem. 58 (15), 8596 (2010). https://doi.org/10.1021/jf101518p
V. A. Shchelkonogov, G. M. Sorokoumova, O. A. Baranova, et al., Biomed. Khim. 62 (5), 577 (2016).
N. Yu. Nikitenko, V. Kh. Shavratskii, A. A. Boldyrev, et al., Vopr. Med. Khim. 41 (1), 41 (1995).
T. N. Fedorova, S. L. Stvolinskii, O. I. Kulikova, et al., Ann. Klin. Eksp. Nevrol. 10 (1), 47 (2016).
E. Yu. Kanyuka and S. G. Zinov’ev, Biokhimiya 79 (1), 110 (2014).
M. Uchiyama and M. Mihara, Anal. Biochem. 86 (1), 271 (1978).
K. P. Shay, R. F. Moreau, E. J. Smith, et al., Biochim. Biophys. Acta 1790 (10), 1149 (2009). https://doi.org/10.1016/j.bbagen.2009.07.026
B. J. Lee and D. G. Hendricks, J. Food Sci. 62 (5), 931 (1997). https://doi.org/10.1111/j.1365-2621.1997.tb15009.x
C. V. Krishnan and M. Garnett, Int. J. Electrochem. Sci., 6, 3607 (2011).
A. R. Smith, S. V. Shenvi, M. Widlansky, et al., Curr. Med. Chem. 11 (9), 1135 (2004). https://doi.org/10.2174/0929867043365387
H. Ihara, Y. Kakihana, A. Yamakage, et al., J. Biol. Chem. 294 (4), 1279 (2019).
K. P. Shay, R. F. Moreau, E. J. Smith, and T. M. Hagen, IUBMB Life 60 (6), 362 (2008).
G. J. Handelman, D. Han, H. Tritschler, and L. Packer, Biochem. Pharmacol. 47, 1725 (1994).
A. V. Lopachev, O. M. Lopacheva, D. A. Abaimov, et al., Biochemistry (Moscow) 81 (5), 511 (2016).
N. Duzgunes and S. Nir, Adv. Drug Delivery Rev. 40, 3 (1999).
ACKNOWLEDGMENTS
The authors are grateful to Abduldzhabbar Balsam Tarek for obtaining liposomal drugs; to the head of Representative office of LIPOID AG Company (Germany) in Moscow Candidate of Chemistry A.V. Symon for providing phosphatidylcholine Lipoid S-100; to Doctor of Biology, Professor of Pirogov Russian National Research Medical University (Ministry of Health of Russian Federation) Yu.O. Teselkin for valuable comments and assistance in writing this article.
Funding
This work was carried out as a part of the State tasks of Pirogov Russian National Research Medical University (State registration no. AAAA-A19-100390063-9) and Research Center of Neurology (State registration no. AAAA-A19-119111290050-6).
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All procedures performed in the study involving human participants were in accordance with the ethical standards of the 1964 Helsinki Declaration and its later amendments. Informed consent for taking biomaterial was obtained from all individual participants involved in the study.
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Translated by A. Barkhash
Abbreviations: LA, lipoic acid; AA, arachidonic acid; DPPC, dipalmitoylphosphatidylcholine; PC, phosphatidylcholine; EI, efficiency of inclusion; TBA-AP, thiobarbituric acid-active products.
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Shchelkonogov, V.A., Darnotuk, E.S., Chekanov, A.V. et al. Liposomal Drug with Carnosine and Lipoic Acid: Preparation, Antioxidant and Antiplatelet Properties. BIOPHYSICS 66, 278–285 (2021). https://doi.org/10.1134/S0006350921020214
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DOI: https://doi.org/10.1134/S0006350921020214