Iron chelators: as therapeutic agents in diseases.

The concentration of iron is tightly regulated, making it an essential element. Various cellular processes in the body rely on iron, such as oxygen sensing, oxygen transport, electron transfer, and DNA synthesis. Iron excess can be toxic because it participates in redox reactions that catalyze the production of reactive oxygen species and elevate oxidative stress. Iron chelators are chemically diverse; they can coordinate six ligands in an octagonal sequence. Because of the ability of chelators to trap essential metals, including iron, they may be involved in diseases caused by oxidative stress, such as infectious diseases, cardiovascular diseases, neurodegenerative diseases, and cancer. Iron-chelating agents, by tightly binding to iron, prohibit it from functioning as a catalyst in redox reactions and transfer iron and excrete it from the body. Thus, the use of iron chelators as therapeutic agents has received increasing attention. This review investigates the function of various iron chelators in treating iron overload in different clinical conditions.

Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis.

Frequent exposure to various external and internal adverse forces (stresses) disrupts cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.

Enzymatic antioxidant system and endothelial function in patients with metabolic syndrome.

BACKGROUND: This study examined the relationship between serum glutathione peroxidase 1 (GPx-1) activity and endothelial dysfunction in the subjects with and without metabolic syndrome (MetS). METHODS: This case-control study was conducted on 76 subjects, 38 were patients with MetS and 38 were without MetS. The demographic, clinical, and laboratory features of the subjects were measured and then compared. The MetS was diagnosed according to the definitions of the National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF). Serum GPx-1 activity was measured by standard methods. Endothelial dysfunction was assessed with flow-mediated dilation (FMD) technique. RESULTS: In case-control study of 76 subjects, all of MetS risk factors including abdominal obesity, triglyceride (TG), low serum level of high-density lipoprotein cholesterol (HDL-C), hypertension (HTN), and fasting plasma glucose (FPG) were significantly higher than healthy individuals (P < 0.050). FMD was significantly lower than normal subjects (P < 0.050). Serum GP-1 activity was significantly lower in patients with MetS compared to normal subjects (21.7 ± 13.5 vs. 79.0 ± 38.6, respectively) (P = 0.001). The value of GPx-1 was significantly correlated with diastolic blood pressure (DBP) (r = -0.249, P = 0.040), C-reactive protein (CRP) (r = -0.409, P = 0.014), and FMD (r = 0.293, P = 0.050) in patients with MetS. The results of logistic regression showed that a unite increase in CRP (mg/dl), FMD (%), and endothelin-1 (ET-1) (pg/ml) and a unit decrease in GPx significantly increased the odds ratio (OR) of MetS; after adjusting for age and sex the results remained significant except for FMD (P < 0.050). CONCLUSION: Endothelial dysfunction is related to serum GPx-1 activity in patients with MetS. GPX-1 activity is associated with risk of cardiovascular diseases (CVDs) and peripheral vascular diseases (PVDs) in patients with MetS.

Relationship between Resistin, Endothelin-1, and Flow-Mediated Dilation in Patient with and without Metabolic Syndrome.

BACKGROUND: Resistin is peptides that signal the functional status of adipose tissue to the brain and other target organs. It causes insulin resistance and affects the vascular endothelial dysfunction. However, the function and relation between resistin in endothelin-1 (ET-1), which leads to the endothelial dysfunction in humans are enigmatic. MATERIALS AND METHODS: In a cross-sectional study of 76 participants (38 metabolic syndrome patients and 38 healthy participants), biochemical and clinical parameters, including lipid profile, fasting glucose, resistin, ET-1, C-reactive protein (CRP), flow-mediated dilation (FMD), and hypertension were determined and compared between the two groups. RESULTS: Multiple linear regression analysis was performed with age- and sex-adjusted plasma resistin levels, FMD, and ET-1 as the dependent variables. Analysis showed that weight, body mass index, triglycerides (TGs), and ET-1 were statistically significant correlated with serum resistin. FMD has negative significantly correlated with weight (r = -0.491, P = 0.001), waist circumference (r = -0.491, P = 0.001), waist-to-hip ratio (r = -0.0444, P = 0.001), and ET-1 (r = -0.075, P = 0.050), but it has significantly correlated with systolic blood pressure (SBP) (r = 0.290, P = 0.016), diastolic blood pressure (DBP) (r = 0.275, P = 0.023), and high-density lipoprotein cholesterol (HDL-C) (r = -0.266, P = 0.050), and ET-1, but it has significantly correlated with SBP, DBP, and HDL-C. ET-1 is significantly correlated with TGs (r = -0.436, P = 0.006), total cholesterol (r = 0.452, P = 0.004), low-density lipoprotein cholesterol (r = 0.454, r = 0.004), and resistin (r = 0.282, P = 0.050), whereas it has negative significantly correlated with HDL-C (r = 0.346, P = 0.034), FMD (r = -0.075, P = 0.050. CONCLUSION: In this study, results shown plasma ET-1 and resistin are suggested as risk factors for the development of endothelial dysfunction and with further study, it is possible that can diagnose the risk of diabetes and cardiovascular disease in the early stages.