Iron overload impact on P-ATPases

Nogueira, Leilismara Sousa; Pessôa, Marco Túlio C.; Costa, Tamara G.F.; Cortes, Vanessa Faria; Santos, Herica L.; Barbosa, Leandro A.

doi:10.1007/s00277-017-3222-4

“…They can compete with other elements and metalloproteins for binding sites and affect cell membrane permeability or other mechanisms. These TEs can promote lipid peroxidation to generate free radicals and participate in electron transport and initiate free radical chain reactions, which leads to changes in blood composition [21][22][23]. Se is a component of many antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and thioredoxin reductase [24].…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Serum Trace Elements and Oxidative Stress of Patients with Different Types of Cancer

Yang

¹

,

Dai

²

,

Chen

³

et al. 2021

Oxidative Medicine and Cellular Longevity

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Objective. Many studies have identified causal and promotive roles of oxidative stress (OxS) and oxidative damage caused by OxS in the occurrence and progression of cancer. Many biomarkers in the blood circulation of patients may change correspondingly with the development of tumors. This study is aimed at investigating the correlation between OxS and serum trace element (TE) levels of patients with different types of cancer. Methods. 1143 different types of cancer patients and 178 healthy controls from Mar. 2018 to Aug. 2020 in Mianyang Central Hospital were involved in this study. Their levels of OxS parameters (including total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI)) and the concentrations of serum TEs (including Cu, Zn, Fe, and Se) were determined. Results. Compared with healthy controls, all types of cancer patients had higher TOS level (all P adj < 0.001 ) and OSI level ( z = 6.228 ~ 9.909 , all P adj < 0.001 ) and lower TAS level (all P adj < 0.001 ). Compared with healthy controls, the changes of four TE levels in serum were different in different types of cancer patients, among which Cu increased in all groups, but there was no statistical difference in gastric and brain cancer; Se decreased in all groups, but there was no statistical difference in gastric, colorectal, esophageal, and other cancer; Zn was significantly decreased in breast cancer patients ( P adj < 0.001 ); there was no statistical difference in the change of Fe in liver, kidney, and other cancer. Spearman correlation showed that the change of Cu concentration was most closely related to the three OxS parameters and was strongly correlated in the observed several types of tumors ( r s > 0.6 ). Multinomial logistic regression showed that the risks of different tumors are related to the level change of multiple TEs and OxS parameters ( OR TOS = 1.19 ~ 2.82 , OR OSI = 2.56 ~ 4.70 , OR TAS = 0.20 ~ 0.46 , OR Cu = 0.73 ~ 1.44 , OR Zn = 0.81 ~ 0.91 , OR Fe = 0.68 ~ 1.18 , and OR Se = 0.22 ~ 0.45 , all P < 0.006 ). Conclusions. The OxS exists in the occurrence and development of cancer, which may be related to the changes of certain trace elements. In order to evaluate OxS correctly, it is necessary to detect TAS and TOS and at the same time, their ratio OSI should be detected. Assessment of markers representing the overall level of OxS and TEs may guarantee improved the monitoring of disease occurrence and development risk in cancer patients.

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“…However, this response depends not only on the ability of the sarcoplasmic reticulum to reuptake, store and release calcium, but also on the calcium efflux mechanisms during the pause of stimuli. Although iron was described as capable of (directly or by ROS generation) inhibiting the calcium reuptake by SERCA2 (Das et al, 2016;Sousa et al, 2018) and the calcium release by the ryanodine receptor (Kim et al, 1995), an equally inhibitory effect on the mechanisms for calcium efflux throughout the membrane (i.e., NCX (Ávila et al, 2016). Furthermore, it was reported that cardiomyocytes derived from induced pluripotent stem cells and exposed to iron overload also had impaired positive inotropic and chronotropic responses to adrenergic stimulation (Lee et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Moderate‐intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats

Ávila

¹

,

Rossi

²

,

Carvalho

³

et al. 2021

Experimental Physiology

4

0

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Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron-overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate-intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60-70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase-MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase.In conclusion, moderate-intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non-pharmacological adjuvant therapy for ironoverload cardiomyopathy.

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“…Hepatic Na + -K + -ATPase activity was measured using an ATPase assay kit (Nanjing Jiancheng Biotechnology Institute, Nanjing, China). The measurement of the Na + -K + -ATPase activity was based on the quantification of inorganic phosphate that is formed by adenosine triphosphate decomposition[15].…”

Section: Methodsmentioning

confidence: 99%

Effects of positive acceleration (+Gz stress) on liver enzymes, energy metabolism, and liver histology in rats

Shi

¹

,

Wang

²

,

Duan

³

et al. 2019

WJG

5

0

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BACKGROUNDExposure to high sustained +Gz (head-to-foot inertial load) is known to have harmful effects on pilots’ body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined.AIMTo investigate rat liver function changes in response to repeated +Gz exposure.METHODSNinety male Wistar rats were randomly divided into a blank control group (BC group, n = 30), a +6 Gz/5 min stress group (6GS group, n = 30), and a +10 Gz/5min stress group (10GS group, n = 30). The 6GS and 10GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure (for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury by measuring the portal venous flow volume, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), liver tissue malondialdehyde (MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures.RESULTSAfter repeated +Gz exposures in the 6GS and the 10GS groups, the velocity and flow signal in the portal vein (PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6GS group had a much higher portal venous flow volume than the 10GS group at 0 h after exposure. The 6GS group had significantly lower ALT, AST, and MDA values than the 10GS group 0 h and 6 h post exposure. The Na+-K+-ATPase activity in the 6GS group was significantly higher than that in the 10GS group 0 h and 6 h post exposure. Hepatocyte injury, determined pathologically, was significantly lower in the 6GS group than in the 10GS group.CONCLUSIONRepeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.

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Iron overload impact on P-ATPases

Cited by 18 publications

References 92 publications

The Relationship between Serum Trace Elements and Oxidative Stress of Patients with Different Types of Cancer

The Relationship between Serum Trace Elements and Oxidative Stress of Patients with Different Types of Cancer

Moderate‐intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats

Effects of positive acceleration (+Gz stress) on liver enzymes, energy metabolism, and liver histology in rats

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