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.

Assessment of the circulatory concentrations of cathepsin D, cathepsin K, and alpha-1 antitrypsin in patients with knee osteoarthritis.

BACKGROUND: Evidence has shown that cysteine protease enzymes, such as cathepsin D, cathepsin A, cathepsin K, and alpha-1 antitrypsin (AAT) are involved in the chronic degenerative joint process. This study aimed to determine the potential involvement of cathepsin K, cathepsin D, and AAT in patients with osteoarthritis (OA). METHODS: This study was performed on 31 patients with knee OA and 29 age- and sex-matched healthy subjects (both with Fars ethnicity from Iran). American College of Rheumatology (ACR) criteria were used to diagnose OA patients. The clinical status of the patients was scored by Western Ontario McMaster Universities Osteoarthritis (WOMAC), and pain intensity was measured by the Visual Analog Scale (VAS). The serum level of AAT was measured using high-resolution cellulose acetate electrophoresis. Additionally, serum levels of cathepsin D and cathepsin K were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The findings showed that the serum level of cathepsin K was significantly increased in OA patients compared to healthy subjects (P = 0.01), while there was no significant difference between serum level of cathepsin D in study groups (P = 0.2). In addition, the serum concentration of AAT was significantly decreased in OA patients compared to healthy subjects (P = 0.003). There was a significant correlation between WOMAC score and age (r = 0.644, P = 0.0001) and VAS (r = 0.866, P < 0.0001) in OA patients. CONCLUSIONS: The decreased level of AAT in OA patients and a rise in serum level of cathepsin K are involved in the pathogenesis of OA via stimulation of bone resorption and cartilage degradation.

The investigation of the frequency of the alpha-1-antitrypsin phenotype in patients with liver cirrhosis.

OBJECTIVES: Alpha-1-antitrypsin (AAT) has different phenotypes. Evidence suggests that the abundance of each of these phenotypes may be associated with a disease. The purpose of this study was to evaluate the frequency of AAT phenotypes in patients with liver cirrhosis as well as in healthy individuals. METHODS: In this study, 42 patients with liver cirrhosis were selected. The results of the previous research done by the researcher on healthy individuals were used to construct the control group. After obtaining informed consent, 5 mL of fasting venous blood sample was taken, and phenotypes were analyzed by isoelectric focusing. Data were analyzed using Chi-square and Fisher's exact tests at a significant level of 0.05. RESULTS: The results of this study indicated that all 42 healthy subjects had an MM allele (100%). However, among 42 patients, 35 (83.3%) had an MM allele, 5 (11.9%) had an MS allele, and 2 (4.8%) had MZ allele. The difference between the two groups was significant (p=0.02). There was no difference between men and women in the allele type (p=0.557). CONCLUSIONS: This study revealed that MS and MZ alleles were observed only in patients with liver cirrhosis, and none of these alleles were found in healthy subjects. Therefore, MS and MZ alleles can be further investigated as risk factors for liver cirrhosis.

The Effects of Hydro-Alcoholic Extract of Fenugreek Seeds on the Lipid Profile and Oxidative Stress in Fructose-Fed Rats.

BACKGROUND: Metabolic syndrome (MetS) is a complex clinical disorder that can lead to an increase in oxidative stress. Patients with this syndrome are at risk of diabetes and cardiovascular disease. The Trigonella foenum-graecum L. (fenugreek) plant has many therapeutic effects, including anti-diabetic and antioxidant. The present study aimed to investigate the effects of the hydro-alcoholic extract of fenugreek seeds (HEFS) on dyslipidemia and oxidative stress due to high-fructose diet-induced MetS. METHODS: In this experimental study, to induce MetS, animals received water containing 20% fructose for 8 weeks. After induction of MetS, 48 male Wistar rats (200-250 g) were randomized into six groups. HEFS was administered to animals at doses of 100 and 200 mg/kg orally for 4 weeks. Animal blood samples were collected to measure biochemical and antioxidant parameters of fasting plasma glucose (FPG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), malondialdehyde (MDA), glutathione peroxidase (GPX), catalase (CAT), and total antioxidant capacity (TAC). RESULTS: The findings showed that the serum levels of FPG, TC, LDL-C, TG, and MDA were significantly reduced in HEFS-exposed groups compared with the control group (P<0.05). Also, significant increases in HDL-C, GPX, CAT, and TAC levels (P<0.05) were observed. CONCLUSION: Our results revealed that treatment with HEFS increases the levels of antioxidant enzymes, decreases FPG level, and at the same time, modifies the lipid profile in MetS. Therefore, HEFS may help to alleviate the risk of some chronic complications of this disease.

The effect of hydroalcoholic Berberis integerrima fruits extract on the lipid profile, antioxidant parameters and liver and kidney function tests in patients with nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the hepatic disorders which is characterized by increasing fat deposits in the liver. This disorder may lead to elevation the activity of liver enzymes and is associated with obesity, dyslipidemia, hypertension, and type II diabetes. The aim of present study was to investigate the effect of Berberis integerrima extract on NAFLD patients compare to placebo. METHODS: The present clinical trial was performed on 42 NAFLD patients who were randomly divided into two groups. The case group received a capsule (750 mg) containing hydro-alcoholic extract of Berberis integerrima extract every 12 h for 2 months, while the control (placebo) group received a capsule containing cellulose. Baseline characteristics, biochemical factors, antioxidant parameter, functional liver and renal test were evaluated before and after the treatment. RESULTS: Comparison rate of different parameters in case group before and after treatment demonstrated that BMI, cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal parameters such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were significantly decreased while HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly elevated. The comparison of the mean parameters difference in two groups indicated that cholesterol, triglyceride, LDL-C, fasting blood glucose, liver enzymes and renal factors were significantly decreased, however HDL-C, glutathione peroxidase enzyme, and total antioxidant capacity were significantly increased in case group compared to control group. CONCLUSION: The study findings revealed that the Berberis integerrima extract could reduce biochemical factors of blood, except HDL-C and increases total antioxidant capacity and glutathione peroxidase enzyme. Therefore, hydro-alcoholic extract of Berberis integerrima may be used as a great supplementary medicine in treating NAFLD.