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Updated: Jun 27, 2025
High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
Evaluation of Ouabain's Tissue Distribution in C57/Black Mice Following Intraperitoneal Injection, Using
Denis A Abaimov1, Rogneda B Kazanskaya1,2, Ruslan A Ageldinov3
1Research Center of Neurology, Volokolamskoye Shosse 80, 125367 Moscow, Russia.
Abstract:
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: Cmax = 882.88 ± 21.82 ng/g; Tmax = 0.08 ± 0.01 h; T1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: Cmax = 145.24 ± 44.03 ng/g (undetectable at 60 min); Tmax = 0.08 ± 0.02 h; T1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: Cmax = 1072.3 ± 260.8 ng/g; Tmax = 0.35 ± 0.19 h; T1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: Cmax = 2558.0 ± 382.4 ng/g; Tmax = 0.35 ± 0.13 h; T1/2 = 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.
Insights
Ouabain, a cardiotonic steroid, does not cross the brain-blood barrier (BBB) in mice, unlike digoxin. This finding suggests ouabain may offer a safer alternative for heart failure treatment by avoiding central nervous system side effects.
Area of Science:
- Pharmacology
- Neuroscience
- Cardiology
Background:
- Cardiotonic steroids (CTSs) like digoxin are vital for heart failure treatment.
- Digoxin's ability to cross the brain-blood barrier (BBB) can lead to central nervous system (CNS) side effects.
- Developing BBB-impermeable CTSs is crucial for enhanced clinical applicability and reduced CNS risks.
Purpose of the Study:
- To investigate the tissue distribution of ouabain after intraperitoneal injection in mice.
- To determine if ouabain penetrates the BBB.
Main Methods:
- Ouabain concentrations were measured in brain, heart, liver, kidney tissues, and plasma of C57/black mice post-injection using HPLC-MS.
- Measurements were taken at multiple time points (5 min to 24 h) after a 1.25 mg/kg intraperitoneal dose.
Main Results:
- Ouabain was undetectable in brain tissue, indicating it does not cross the BBB.
- Ouabain showed rapid elimination from plasma and cardiac tissue.
- High concentrations were observed in kidney and liver tissues, with varying elimination rates.
Conclusions:
- Ouabain does not cross the BBB in mice, differentiating it from digoxin.
- Ouabain's rapid systemic elimination suggests potential advantages for systemic administration in heart failure.
- Intracerebral administration is necessary for studying ouabain's CNS effects due to its BBB impermeability.
