Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium

Ávila, Renata Andrade; Silva, Marito A. S. C.; Peixoto, João Victor Capelli; Kassouf-Silva, Ilana; Fogaça, R. T. H.; Santos, Leonardo dos

doi:10.1016/j.tiv.2016.07.003

Cited by 17 publications

(6 citation statements)

References 37 publications

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“…As expected, a previous study found that Ca V 3.1 TTCC was a significant portal for Fe 2+ entry into cells leading to an iron overload condition49. Consistent with a recent study indicated that at a high concentration of free Fe 2+ may compete with a Ca 2+ influx into the myocardium through Ca 2+ channels by both LTCC and TTCC50. Our previous study also found that TTCC is an important pathway for Fe 2+ entry into the heart of thalassemic mice under iron overload conditions171819.…”

Section: Discussionsupporting

confidence: 86%

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Wongjaikam

Kumfu

Khamseekaew

et al. 2017

Sci Rep

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Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats.

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Section: Discussionsupporting

confidence: 86%

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Wongjaikam

Kumfu

Khamseekaew

et al. 2017

Sci Rep

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“…Copper leads to the formation of free radicals from the chemical reactions of Fenton and Haber-Weiss [44]. Previous reports have shown that oxidative stress development is the main mechanism by which copper impairs cardiac contractility [45][46][47][48][49][50][51]. Based on this, we performed a detailed assessment of each of the regulatory mechanisms of cardiac contractility to describe a model of cardiotoxicity induced by exposure to increasing levels of copper.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

et al. 2023

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Copper is essential for homeostasis and regulation of body functions, but in excess, it is a cardiovascular risk factor since it increases oxidative stress. The objective of this study was to evaluate the effects of exposure to the recommended daily dose (13 µg/kg/day), upper tolerable dose (0.14 mg/kg/day) and twice the upper tolerable dose (0.28 mg/kg/day) via i.p. over 4 weeks on the vascular reactivity of aortic rings and the contraction of LV papillary muscles. It was also determined whether the antioxidant peptide from egg white hydrolysate (EWH) prevents these effects. Copper exposure at the doses evaluated did not change weight gain, the reactivity of the aortic rings or the cardiac mass. The dose of 0.13 µg/kg/day did not reduce the force of contraction, but it impaired the time derivatives of force. Doses of 0.14 and 0.28 mg/kg/day reduced the force of contraction, the inotropic response to calcium and isoproterenol, the postrest contraction and the peak and plateau of tetanized contractions. EWH treatment antagonized these effects. These results suggest that copper, even at the dose described as upper tolerable, can impair cardiac contraction without altering vascular reactivity. Antioxidative stress therapy with EWH reversed these harmful effects, suggesting a possible strategy for the amelioration of these effects.

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“…Ávila et al. (2016) reported that the productions of OH . and H 2 O 2 by isolated rat papillary muscle were increased and the contractility was reduced by increasing ferrous iron concentrations.…”

Section: Discussionmentioning

confidence: 99%

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status

et al. 2017

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If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll‐like receptor‐9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF‐α and IL‐1β. In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham‐operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF‐α and gene expression of IL‐1β and TNF‐α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF‐α and IL‐1β on the cardiac function is known to occur at very high concentrations. The influence of low‐ to moderate‐grade inflammation on the myocardial mechanical behavior must thus be revisited.

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Mechanisms involved in the in vitro contractile dysfunction induced by different concentrations of ferrous iron in the rat myocardium

Cited by 17 publications

References 37 publications

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

Cardiovascular Harmful Effects of Recommended Daily Doses (13 µg/kg/day), Tolerable Upper Intake Doses (0.14 mg/kg/day) and Twice the Tolerable Doses (0.28 mg/kg/day) of Copper

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status

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