Aging is associated with increased brain iron through cortex-derived hepcidin expression

Iron is an essential molecule for biological processes, but its accumulation can lead to oxidative stress and cellular death. Due to its oxidative effects, iron accumulation is implicated in the process of aging and neurodegenerative diseases. However, the mechanism for this increase in iron with aging, and whether this increase is localized to specific cellular compartment(s), are not known. Here, we measured the levels of iron in different tissues of aged mice, and demonstrated that while cytosolic non-heme iron is increased in the liver and muscle tissue, only the aged brain cortex exhibits an increase in both the cytosolic and mitochondrial non-heme iron. This increase in brain iron is associated with elevated levels of local hepcidin mRNA and protein in the brain. We also demonstrate that the increase in hepcidin is associated with increased ubiquitination and reduced levels of the only iron exporter, ferroportin-1 (FPN1). Overall, our studies provide a potential mechanism for iron accumulation in the brain through increased local expression of hepcidin, and subsequent iron accumulation due to decreased iron export. Additionally, our data support that aging is associated with mitochondrial and cytosolic iron accumulation only in the brain and not in other tissues.

Fibrates: A Possible Treatment Option for Patients with Abdominal Aortic Aneurysm?

Abdominal aortic aneurysm (AAA) is a life-threatening disease; however, there is no established treatment for patients with AAA. Fibrates are agonists of peroxisome proliferator-activated receptor alpha (PPARα) that are widely used as therapeutic agents to treat patients with hypertriglyceridemia. They can regulate the pathogenesis of AAA in multiple ways, for example, by exerting anti-inflammatory and anti-oxidative effects and suppressing the expression of matrix metalloproteinases. Previously, basic and clinical studies have evaluated the effects of fenofibrate on AAA. In this paper, we summarize the results of these studies and discuss the problems associated with using fenofibrate as a therapeutic agent for patients with AAA. In addition, we discuss a new perspective on the regulation of AAA by PPARα agonists.

Anti-aging and anti-carcinogenic effects of 1α, 25-dihyroxyvitamin D3 on skin

Photoaging and carcinogenesis are facilitated by oxidative stress, inflammation, angiogenesis, and extracellular matrix (ECM) remodeling. Oxidative effects include DNA damage, membrane oxidation, lipid peroxidation, and alterations in the expression of p53 and antioxidant enzymes. The inflammatory and angiogenesis mediators include interleukin-1, tumor necrosis factor-α, interleukin-8, transforming growth factor-β, and vascular endothelial growth factor. ECM remodeling includes alterations in the expression and organization of collagen, elastin, matrix metalloproteinases, and elastase. 1α, 25-dihydroxy-vitamin D3 has antioxidant, anti-inflammatory, and ECM regulatory properties, and can counteract the processes that facilitate photoaging and carcinogenesis. This review provides an overview of the beneficial effects of vitamin D supplementation at a molecular level, followed by a brief discussion regarding its use as a supplement.

Therapeutic potential of resveratrol in diabetic nephropathy according to molecular signaling

Background: Diabetic nephropathy (DN) as a severe complication of diabetes mellitus (DM), is a crucial menace for human health and survival and remarkably elevates the healthcare systems’ costs. Therefore, it is worth noting to identify novel preventive and therapeutic strategies to alleviate the disease conditions. Resveratrol, as a well-defined anti-diabetic/ antioxidant agent has capabilities to counteract diabetic complications. It has been predicted that resveratrol will be a fantastic natural polyphenol for diabetes therapy in the next few years. Objective: Accordingly, the current review aims to depict the role of resveratrol in the regulation of different signaling pathways that are involved in the reactive oxygen species (ROS) production, inflammatory processes, autophagy, and mitochondrial dysfunction, as critical contributors to DN pathophysiology. Results: The pathogenesis of DN can be multifactorial; hyperglycemia is one of the prominent risk factors of DN development that is closely related to oxidative stress. Resveratrol, as a well-defined polyphenol, has various biological and medicinal properties, including anti-diabetic, anti-inflammatory, and anti-oxidative effects. Conclusion : Resveratrol prevents kidney damages that are caused by oxidative stress, enhances antioxidant capacity, and attenuates the inflammatory and fibrotic responses. For this reason, resveratrol is considered an interesting target in DN research due to its therapeutic possibilities during diabetic disorders and renal protection.

Oxidative Effects in Streptozotocin-induced Male and Female Mice: The Effect of Garlic Oil and Melatonin

Background: Recent studies have revealed that a hyperglycemia-induced overproduction of superoxide can be the first event in the activation of all pathways involved in the pathogenesis of complications of diabetes. Supplementation of garlic was found to decrease diabetes-induced oxidative stress complications. Studies shown also that melatonin attenuates diabetes‐induced oxidative stress in diabetic induced rabbits and rats. Objective: In this present study, oxidative stress in diabetic model and the effect of garlic oil or melatonin treatment were examined in both genders' male and females' mice. Methods: 96 mice were randomly divided into 5 groups including control (C), diabetic (D), melatonin 10 mg/kg (D+M), garlic extract 100 mg/kg (D+G) and combined melatonin and garlic (D+M+G). All treatments were given orally daily for 16 weeks after induction of hyperglycemia by streptozocin (STZ). Fasting blood glucose and antioxidant levels were estimated. Results: Streptozotocin induced diabetic mice, showed a significant increase of plasma glucose, lipid peroxide and uric acid. Accordingly, significant decreases in the levels of antioxidants ceruloplasmin were found in the plasma of diabetic mice. Treatment of diabetic mice with garlic oil or melatonin for 16 weeks significantly increased plasma levels of ceruloplasmin activities. Lipid peroxides, uric acid, blood glucose was decreased significantly after treatment with garlic oil or melatonin. Conclusion: The results suggest that garlic oil or melatonin may effectively normalize the impaired antioxidants status in streptozotocin induced diabetes in both males and females mice.

Response of Cardiac Tissue Oxidative Stress After Aerobic Exercise and Capsaicin Administrations in Rats Fed High-Fat Diet

Background: Oxidative stress harms cells and impairs the balance between oxidative and antioxidative factors. Exercise and capsaicin have anti-inflammatory and antioxidant effects, as well as some benefits on the cardiovascular system. Objectives: The aim of the present study was to examine the effect of aerobic training with capsaicin on heart changes oxidative stress in rats fed a high-fat diet (HFD). Methods: In this experimental study, 40 male Wistar rats were fed a normal diet (ND, n = 8) or HFD (n = 32) for 8 weeks. After eight weeks, all rats were divided into five groups: ND, HFD, high-fat diet-training (HFDT), high-fat diet-capsaicin (HFDCap), high-fat diet-training-capsaicin (HFDTCap). Training groups performed a progressive aerobic running program (at 15 - 25 m/min, 30 - 60 min/day, and 5 days/week) on a motor-driven treadmill for eight weeks. Capsaicin (4 mg/kg/day) was administered orally, by gavage, once a day. Results: The results showed significant increase in cardiac SOD, GPx and CAT levels in HFDT (P < 0.001), HFDCap (P < 0.001) and HFDTCap (P < 0.001) groups. Also, a significant increase in the amount of this index was observed in the HFDTCap compared to the HFDT and HFDCap groups (P < 0.05). The level of malondialdehyde (MDA) in all experimental groups was significantly lower than the HFD group (P < 0.001). Conclusions: Exercise and capsaicin improve HFD-induced oxidative stress. Therefore, exercise and capsaicin can be used as an appropriate alternative treatment for obesity and its associated inflammatory and oxidative effects.

Effects of mulberry extract on the liver pathology and serum biochemical parameters in carmustine administrated rats

BACKGROUND: Carmustine is a chemotherapeutic agent that is mainly used in the treatment of glioblastoma and can cause toxic effects on various organs, including the liver. The white mulberry extract has anti-apoptotic and anti-oxidant effects. OBJECTIVE: The study aimed at investigating the effects of the dried white mulberry extract on the pathology, apoptosis, and oxidative stress in the liver, as well as the levels of serum adenosine deaminase, glutathione peroxidase, superoxide dismutase, ceruloplasmin, paraoxonase, and malondialdehyde in carmustine-administrated rats. METHODS: Forty-two rats divided into six groups were used in this study. BCNU was administrated intraperitoneally (IP) (5 mg/kg body weight (BW)/week) for 10 weeks to the BCNU and BCNU-DWME groups. DWME was administered (600 mg/kg-BW by oral gavage) daily for 10 weeks to the DWME and BCNU-DWME groups. After the experimental procedure, histopathological, immunohistochemical, and biochemical analyses were performed. RESULTS: Carmustine caused biliary hyperplasia at a dose of 5 mg/kg. However, the mulberry extract was not effective in alleviating this pathology. Furthermore, the administration of carmustine induced apoptosis in hepatocytes, and the mulberry extract had an anti-apoptotic effect. Carmustine increased the 8-OHdG activity in the liver, and dried mulberry extract ameliorated this activity. Although there was no significant difference in the serum oxidative stress parameters between the groups, carmustine significantly increased the adenosine deaminase activity during the recovery period, while mulberry extracts partially ameliorated these effects in the recovery period. CONCLUSIONS: Dried white mulberry extract has anti-apoptotic and anti-oxidative effects against carmustine-induced toxicity.

Evaluation of the Anti-Inflammatory and Anti-Oxidative Effects of Therapeutic Human Lactoferrin Fragments

Chronic inflammation is considered a pressing health issue that needs resolving. Inflammatory disease such as inflammatory bowel disease requires a long-term medical regimen to prevent disease progression. Conventionally, lactoferrin is used to treat mild gastrointestinal tract and skin inflammation. Protease-digested lactoferrin fragments often exhibit improved therapeutic properties compared to full-length lactoferrin (flHLF). However, there are no studies on the use of protease-digested lactoferrin fragments to treat inflammation. Herein, we assess the anti-inflammatory properties of engineered recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colonic fibroblast cells and colorectal cancer cells. We found that rtHLF4 is 10 times more effective to prevent inflammation compared to flHLF. These results were investigated by looking into the reactive oxygen species (ROS) production, angiogenesis activity, and cellular proliferation of the treated cells. We have demonstrated in this study the anti-inflammatory properties of the flHLF and the various lactoferrin fragments. These results complement the anti-cancer properties of these proteins that were demonstrated in an earlier study.

In Vivo Hypoglycemic Effects, Potential Mechanisms and LC-MS/MS Analysis of Dendropanax Trifidus Sap Extract

Extracts of medicinal plants have been widely used to benefit human health. Dendropanax morbiferus (DM) has been well-studied for its anti-inflammatory and anti-oxidative effects, while Dendropanax trifidus (DT) is a lesser-known ecotype phylogenetically similar to DM, which has received significantly less attention. Studies thus far have primarily focused on leaf and bark extracts of DM, and not much is yet known about the properties of either DM or DT sap. Therefore, here we performed in vivo toxicity and efficacy studies, in order to assess the biological effects of DT sap. To establish a safe dosage range, single dose or two-week daily administrations of various concentrations were performed for ICR mice. Measurements of survival ratio, body/organ weight, blood chemistry, histochemistry and Western blots were performed. A concentration of ≤0.5 mg/g DT sap was found to be safe for long-term administration. Interestingly, DT sap significantly reduced blood glucose in female mice. In addition, increasing concentrations of DT sap decreased phosphorylated (p) insulin receptor substrate (IRS)-1(ser1101)/IRS-1 in liver tissues, while increasing pAMP-activated protein kinase (AMPK)/AMPK in both the liver and spleen. To analyze its components, liquid chromatography-tandem mass spectrometry of DT sap was performed in comparison with Acer saccharum (AS) sap. Components such as estradiol, trenbolone, farnesol, dienogest, 2-hydroxyestradiol and linoleic acid were found to be highly enriched in DT sap compared to AS sap. Our results indicate DT sap exhibits hypoglycemic effects, which may be due to the abundance of the bioactive components.