| Autor: |
Abaimov DA; Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia., Kazanskaya RB; Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia.; Biological Department, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia., Ageldinov RA; Scientific Center for Biomedical Technologies of the Federal Biomedical Agency of Russia, 119435 Krasnogorsk, Russia., Nesterov MS; Scientific Center for Biomedical Technologies of the Federal Biomedical Agency of Russia, 119435 Krasnogorsk, Russia., Timoshina YA; Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia.; Biological Department, Lomonosov Moscow State University, Leninskiye Gory 1, 119991 Moscow, Russia., Platova AI; The Mental Health Research Center, Kashirskoye Shosse 34, 115522 Moscow, Russia., Aristova IJ; Biological Department, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia.; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia., Vinogradskaia IS; Non-State Private Educational Institution of Higher Professional Education, Moscow University for Industry and Finance 'Synergy', Meshchanskaya Street, 9/14, Building 1, 129090 Moscow, Russia., Fedorova TN; Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia., Volnova AB; Biological Department, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia.; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia., Gainetdinov RR; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia.; Saint-Petersburg University Hospital, 199034 St. Petersburg, Russia., Lopachev AV; Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia.; Institute of Translational Biomedicine, Saint Petersburg State University, Universitetskaya Emb. 7/9, 199034 St. Petersburg, Russia. |
| Abstrakt: |
Cardiotonic steroids (CTSs), such as digoxin, are used for heart failure treatment. However, digoxin permeates the brain-blood barrier (BBB), affecting central nervous system (CNS) functions. Finding a CTS that does not pass through the BBB would increase CTSs' applicability in the clinic and decrease the risk of side effects on the CNS. This study aimed to investigate the tissue distribution of the CTS ouabain following intraperitoneal injection and whether ouabain passes through the BBB. After intraperitoneal injection (1.25 mg/kg), ouabain concentrations were measured at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h using HPLC-MS in brain, heart, liver, and kidney tissues and blood plasma in C57/black mice. Ouabain was undetectable in the brain tissue. Plasma: C max = 882.88 ± 21.82 ng/g; T max = 0.08 ± 0.01 h; T 1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: C max = 145.24 ± 44.03 ng/g (undetectable at 60 min); T max = 0.08 ± 0.02 h; T 1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: C max = 1072.3 ± 260.8 ng/g; T max = 0.35 ± 0.19 h; T 1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: C max = 2558.0 ± 382.4 ng/g; T max = 0.35 ± 0.13 h; T 1/2 = 1.24 ± 0.7 h; MRT = 0.98 ± 0.33 h. Unlike digoxin, ouabain does not cross the BBB and is eliminated quicker from all the analyzed tissues, giving it a potential advantage over digoxin in systemic administration. However, the inability of ouabain to pass though the BBB necessitates intracerebral administration when used to investigate its effects on the CNS. |
