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. 2018 Mar;14(2):46-52.
doi: 10.22122/arya.v14i2.1642.

The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats

Beydolah Shahouzehi  1 , Hamid Reza Nasri  2 , Yaser Masoumi-Ardakani  3
Affiliations

The effect of different digoxin concentrations on heart tissue and antioxidant status in iron-overloaded rats

Beydolah Shahouzehi et al. ARYA Atheroscler. 2018 Mar.

Abstract

Background: Thalassaemia is a hereditary disorder and has an economic burden on patients and the government. The most prevalent complication in these patients is iron overload which is followed by cardiomyopathy. Digoxin is considered as a treatment against heart failure in thalassaemia. The present study evaluated the effect of two digoxin concentrations on iron content and antioxidative defense in cardiac tissue of iron-overloaded rats.

Methods: The study was conducted on 48 rats which were divided into 6 groups. Group 1 was the control group and did not receive any treatment and group 2 was the iron overload group. In addition groups 3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS) were assessed in cardiac tissues.

Results: Co-administration of iron-dextran and digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P < 0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron overload groups. GPX levels significantly reduced in groups 5 and 6 (iron + digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron control group.

Conclusion: Digoxin remarkably facilitates iron uptake by cardiomyocytes by affecting other channels such as L-type and T-type Ca2+ channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model deteriorated antioxidative parameters and increased iron entry into heart tissue at higher doses. Therefore, in patients with beta thalassaemia major, digoxin must be administered with great care and serum iron and ferritin must be regularly monitored.

Keywords: Digoxin; Glutathione Peroxidase; Iron Overload; Superoxide Dismutase.

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Figures

Figure 1
Figure 1
Cardiac iron contents in different studied groups. Data is expressed as mean ± SEM. SEM: Standard error of mean * Statistically significant compared to control group, # Statistically significant compared to iron overload control group, ‡ statistically significant compared to iron-dextran + digoxin 1 group
Figure 2
Figure 2
Malondialdehyde levels in heart tissue of rats in different studied groups Data is expressed as mean ± SEM. SEM: Standard error of mean MDA: Malondialdehyde * Statistically significant compared to control group, # Statistically significant compared to iron overload control group, ‡ statistically significant compared to iron-dextran + digoxin 1 group.
Figure 3
Figure 3
Superoxide dismutase levels in heart tissue of rats in different studied groups. Data is expressed as mean ± SEM. SEM: Standard error of mean SOD: Superoxide dismutase * Statistically significant compared to control group, # Statistically significant compared to iron overload control group, ‡ Statistically significant compared to iron-dextran + digoxin 1 group
Figure 4
Figure 4
Glutathione peroxidase in heart tissue of rats in different studied groups Data is expressed as mean ± SEM. SEM: Standard error of mean GPX: Glutathione peroxidase * Statistically significant compared to control group, # Statistically significant compared to iron overload control group, ‡ Statistically significant compared to iron-dextran + digoxin 1 group
Figure 5
Figure 5
Total antioxidant status quantity in heart tissue of rats in different studied groups. Data is expressed as mean ± SEM. SEM: Standard error of mean TAS: Total antioxidant status * Statistically significant compared to control group, # Statistically significant compared to iron overload control group
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