TY - JOUR

T1 - Evaluation of Ouabain’s Tissue Distribution in C57/Black Mice Following Intraperitoneal Injection, Using Chromatography and Mass Spectrometry

AU - Абрамов , Денис

AU - Казанская, Рогнеда Борисовна

AU - Тимошина, Юлия Анатольевна

AU - Аристова, Ирина Юрьевна

AU - Федорова, Татьяна

AU - Вольнова, Анна Борисовна

AU - Лопачев, Александр Васильевич

PY - 2024/4/13

Y1 - 2024/4/13

N2 - 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.

AB - 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.

KW - Animals

KW - Blood-Brain Barrier/metabolism

KW - Brain/metabolism

KW - Cardiotonic Agents/pharmacokinetics

KW - Chromatography, High Pressure Liquid/methods

KW - Injections, Intraperitoneal

KW - Kidney/metabolism

KW - Liver/metabolism

KW - Male

KW - Mass Spectrometry/methods

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocardium/metabolism

KW - Ouabain

KW - Tissue Distribution

KW - brain–blood barrier

KW - ouabain

KW - cardiotonic steroids

KW - liver

KW - digoxin

KW - brain

KW - kidney

KW - blood plasma

KW - cardiac tissue

UR - https://www.mendeley.com/catalogue/e38a765e-43a7-3691-8098-cf001b02dfb3/

U2 - 10.3390/ijms25084318

DO - 10.3390/ijms25084318

M3 - Article

C2 - 38673903

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 8

M1 - 4318

ER -