Abstract
Accumulating evidence shows that iron overload is a new risk factor for diabetes mellitus. l-type Ca2+ channel (LTCC) has been identified as an important mediator for ferrous iron uptake into cardiomyocytes. In this study, we aimed to examine the effects of verapamil, the LTCC blocker, on myocardial iron metabolism in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozocin after intragastric administration of fat emulsion, and then treated by verapamil (5 mg · kg−1 · day−1) for 1 week. The results showed that verapamil did not alter the blood glucose level of diabetic rats. However, elevated levels of superoxide dismutase, malonaldehyde, and serum ferritin in diabetic rats were decreased significantly by verapamil treatment. Moreover, serum, myocardial, and urine iron were elevated remarkably along with a decrease of hepatic iron in diabetic rats. After verapamil administration, serum and myocardial iron in diabetic rats were reduced significantly but urine and hepatic iron were increased. Furthermore, confocal microscopy demonstrated that intracellular-free iron concentration was elevated dramatically in cardiomyocytes of diabetic rats, which was markedly attenuated after verapamil treatment. In summary, our data demonstrated that verapamil prevented myocardial iron overload by inhibiting intracellular iron accumulation in diabetic cardiomyocytes.
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This work was supported by the research grant (no. 1154z1008) from Education Department of Heilongjiang Province of China.
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Hong-li Shan and Yan Wang contributed equally to this work.
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Shan, Hl., Wang, Y., Wu, Jw. et al. Verapamil reverses cardiac iron overload in streptozocin-induced diabetic rats. Naunyn-Schmiedeberg's Arch Pharmacol 386, 645–650 (2013). https://doi.org/10.1007/s00210-013-0863-2
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DOI: https://doi.org/10.1007/s00210-013-0863-2