High doses of digoxin increase the myocardial nuclear factor-kB and CaV1.2 channels in healthy mice. A possible mechanism of digitalis toxicity - 11/07/18
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Graphical abstract |
Highlights |
• | Digoxin was administered (0.1, 1 or 5 mg/kg) orally daily for seven days. |
• | Serum digoxin, calcium, and cardiac calcium levels were measured and NF-kB, CaV1.2 channel expression were studied. |
• | Digoxin (1 and 5 mg/kg) increased serum, atrial and ventricular Ca+2 levels. |
• | Digoxin groups (1 and 5 mg/kg/day) showed more expression of both NF-kB and CaV1.2. |
• | NF-kB may be responsible for digoxin toxicity, partially via modulation of CaV1.2. |
Abstract |
Background |
Toxic effects of digoxin may occur with normal therapeutic serum level. However, the underlying mechanisms are not fully understood. Nuclear factor kappa-B (NF-kB) is an important transcription factor in most organ systems and is often implicated in the harmful effects of cardiac injury. NF-kB promotes inflammatory responses, mediates adverse cardiac remodeling and has a function correlation with calcium. The voltage-gated L-type calcium channel CaV1.2 mediates the influx of Ca+2 into the cell in response to membrane depolarization. Our aim was to characterize the role of NF-kB during digoxin toxicity and to assess its correlation with Cav 1.2 in healthy mice in vivo.
Methods |
To address these questions, digoxin was administered in doses of 0.1, 1 or 5 mg/kg orally daily for seven days to the animals. Serum digoxin, serum calcium, atrial and ventricular calcium levels were measured. We, also, looked for NF-kB and CaV1.2 channel expression in cardiac muscle of mice.
Results |
Digoxin at a dose of 0.1 mg/kg did not enhance serum, atrial, and ventricular Ca+2 levels, but were increased when digoxin dose of 1 and 5 mg/kg were administered. Histologically, myocardial necrosis and cellular infiltration on day 7 were significantly more severe in the 5 mg/kg/day digoxin group. Immunohistochemical studies showed more expression of both NF-kB and CaV1.2 in 1 and 5 mg/kg/day digoxin groups.
Conclusions |
These data suggest that NF-kB may be responsible for digoxin toxicity, at least partially via modulation of CaV1.2 and intracellular calcium homeostasis in the myocardium.
Le texte complet de cet article est disponible en PDF.Keywords : Calcium, Digoxin, Nuclear factor kappa-B, Ventricular
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Vol 105
P. 533-539 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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