Zinc ionophores isolated from Terminalia bellirica fruit rind extract protect against cardiomyocyte hypoxia/reoxygenation injury.

The study aimed to isolate and characterize zinc ionophores from Terminalia bellirica fruit using a liposome assay and test its utility in H9c2 rat cardiomyoblasts cells subjected to hypoxia/reoxygenation. Ethyl acetate extract that exhibited zinc ionophore activity was resolved to yield three polyphenols that were characterized as epicatechin-3-gallate (ECG), epigallocatechin-3-gallate (EGCG) and epigallocatechin (EGC) by nuclear magnetic resonance and electrospray ionization-mass spectra. The polyphenols enhanced the uptake of zinc into the liposomes and increased FluoZin-3 fluorescence.

Ellagic Acid from Terminalia arjuna Fruits Protects Against Chromium and Cobalt Toxicity in Primary Human Lymphocytes.

Increased accumulation of heavy metal ions such as Cr and Co due to release from prostheses and metallic implants has been reported. These metal ions have been shown to affect both resting and activated lymphocytes. Natural remedies towards mitigating the cytotoxic effects of metal ions are clearly warranted.

Zinc dyshomeostasis in azoxymethane-induced colonic precancerous and cancerous lesions in Fischer rats.

Zinc is an essential micronutrient involved in various biological processes. It is also argued that tumors need zinc for maintenance and proliferation and tumor cell apoptosis. Zinc homeostasis is regulated by the gastrointestinal tract and involves interplay of host, dietary, environmental and social factors such as alcohol consumption.

Andrographolide suppresses cisplatin-induced endothelial hyperpermeability through activation of PI3K/Akt and eNOS -derived nitric oxide.

Cisplatin upregulate the intercellular adhesion molecule expression on the surface of endothelium, which in turn mediates enhanced infiltration by monocytes or leukocytes, resulting in endothelial dysfunction. Here we examined changes induced by andrographolide, a diterpenoid lactone isolated from Andrographis paniculata on endothelial cell activation and hyperpermeability in cisplatin-stimulated endothelial cells. Cisplatin upregulated endothelial ICAM-1 expression, through an NF-κB dependent mechanism, that also required the enhanced translocation of Protein Kinase C-α (PKC) onto the plasma membrane, phosphorylation of transient receptor potential channel 1 (TRPC), leading to store-operated Ca-entry (SOCE), endothelial cell dysfunction and hyperadhesion of U937 monocytes.

Zinc-dependent changes in oxidative and endoplasmic reticulum stress during cardiomyocyte hypoxia/reoxygenation.

Myocardial zinc dyshomeostasis is associated with caspase-3 activation, ErbB2 degradation and apoptosis during hypoxia/reoxygenation. Zinc pyrithione replenishes intracellular zinc, suppresses caspase-3, augments ErbB2 levels and improves cell survival. We hypothesize that zinc is capable of modulating redox and endoplasmic reticulum (ER) stress in the setting of cardiomyocyte hypoxia-reoxygenation.

Dietary phytate lowers - mutational frequency, decreases DNA-adduct and hydroxyl radical formation in azoxymethane-induced colon cancer.

Objectives: Dietary phytate is known to protect against azoxymethane (AOM)-induced preneoplastic lesions. The present study was designed to determine whether dietary phytate affects mutation frequency in colon epithelial cells challenged with azoxymethane , through lowering the formation of O-methyl guanosine (O-MeG) and 8-hydroxy deoxyguanosine (8-OHdG) adducts.

Materials And Methods: We used Fisher F344 rats induced with AOM for 20 weeks and undertook 1% or 2% phytate supplementation for subsequent 16 weeks to monitor the mutation frequencies of one of the candidate genes, K-, along with DNA adduct load.

Biochemical, machine learning and molecular approaches for the differential diagnosis of Mucopolysaccharidoses.

This study was aimed to construct classification and regression tree (CART) model of glycosaminoglycans (GAGs) for the differential diagnosis of Mucopolysaccharidoses (MPS). Two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used for the qualitative and quantitative analysis of GAGs. Specific enzyme assays and targeted gene sequencing were performed to confirm the diagnosis.

Comparative Response of Cardiomyocyte ZIPs and ZnTs to Extracellular Zinc and TPEN.

Intracellular zinc concentrations are tightly regulated by the coordinated regulation of ZIPs and ZnTs. Very little is known about the regulation of these transporters in cardiomyocytes, in response to extracellular zinc. Adult rat cardiomyocytes express ZnTs 1, 2, 5, and 9, in addition to ZIPs 1, 2, 3, 6, 7, 9, 10, 11, 13, and 14.

Low Ctr1p, due to lack of Sco1p results in lowered cisplatin uptake and mediates insensitivity of rho0 yeast to cisplatin.

Copper and cisplatin share copper transporter 1 (Ctr1) for cellular import. Copper depletion increases sensitivity of wild type yeast to cisplatin, whereas mitochondrial DNA-deficient rho0 cells are resistant to cisplatin. In the current study, we sought to determine whether copper deprivation modulates sensitivity of rho0 yeast to cisplatin.

Zinc Dyshomeostasis in Cardiomyocytes after Acute Hypoxia/Reoxygenation.

Zinc dyshomeostasis may play a role in the pathogenesis of myocardial ischemia/reperfusion injury. The objective of this study was to investigate the expression profile of zinc regulated transporter like- and iron-regulated transporter-like proteins (ZIPs) and zinc transporter proteins (ZnTs) in cardiomyocytes and their modulation in response to hypoxia and reoxygenation. Adult rat ventricular myocytes (ARVMs) were subjected to 6 h of hypoxia, followed by 18 h of reoxygenation.

Cisplatin cytotoxicity is dependent on mitochondrial respiration in .

Objectives: To understand the role of mitochondrial respiration in cisplatin sensitivity, we have employed wild-type and mitochondrial DNA depleted Rho0 yeast cells.

Materials And Methods: Wild type and Rho0 yeast cultured in fermentable and non-fermentable sugar containing media, were studied for their sensitivity against cisplatin by monitoring growth curves, oxygen consumption, pH changes in cytosol/mitochondrial compartments, reactive oxygen species production and respiratory control ratio.

Results: Wild-type yeast grown on glycerol exhibited heightened sensitivity to cisplatin than yeast grown on glucose.

Loss of ErbB2-PI3K/Akt signaling prevents zinc pyrithione-induced cardioprotection during ischemia/reperfusion.

Objectives: The purpose of this study was to determine if zinc homeostasis is affected during ischemia/reperfusion, if so, whether zinc pyrithione limits myocardial cell death and improves hemodynamics when administered as an adjunct to reperfusion and if ErbB receptor tyrosine kinases that are important for the long-term structural integrity of the heart are indispensable for reperfusion salvage.

Methods: Isolated perfused rat hearts were subjected to 35min of global ischemia and reperfused for 120min to determine the relative intracellular zinc levels by TSQ staining. The hearts were reperfused in the presence of incremental concentrations of zinc pyrithione for the first 10min during reperfusion.

Intracellular zinc status influences cisplatin-induced endothelial permeability through modulation of PKCα, NF-κB and ICAM-1 expression.

Platinum-based chemotherapeutic regimen induces vascular dysfunction. Action of cisplatin on endothelial cells is mediated by protein kinase C (PKC-α), which further activates nuclear factor-κB (NF-κB) and induces canonical transient receptor potential channel (TRPC1) and intercellular adhesion molecule (ICAM-1) expression. Increased ICAM-1 contributes to hyperadhesion of monocytes and endothelial dysfunction.

Zinc pyrithione inhibits caspase-3 activity, promotes ErbB1-ErbB2 heterodimerization and suppresses ErbB2 downregulation in cardiomyocytes subjected to ischemia/reperfusion.

Heart tissue becomes zinc-depleted and the capacity to mobilize labile zinc is diminished, indicating zinc dyshomeostasis during ischemia/reperfusion (I/R). Apparently, zinc pyrithione restores the basal zinc levels during I/R and prevents apoptosis by activating phosphatidyl inositol-3-kinase/Akt and targeting mitochondrial permeability transition. Receptor tyrosine kinases of the ErbB family (ErbB1 to ErbB4) are cell surface proteins that can regulate cell growth, proliferation and survival.

Silencing of PKC-α, TRPC1 or NF-κB expression attenuates cisplatin-induced ICAM-1 expression and endothelial dysfunction.

Platinum-based chemotherapy has been associated with increased long-term cardiovascular events. Also noteworthy is the accumulating awareness of early vascular toxicity occurring at the time of chemotherapy or immediately thereafter. The objective of the study was to delineate the molecular mechanisms associated with the early vascular toxicity and test the molecular silencing approach towards attenuating the endothelial dysfunction during platinum-based chemotherapy.

In vitro biological evaluation of glyburide as potential inhibitor of collagenases.

In tissues with upregulated MMP activity, MMP inhibition remains one of the key strategies. Potential inhibitors of MMPs have been tested for almost 30 years, but none have reached clinical utility due to bioavailability issues and adverse effects. This study utilized the approach of drug repurposing for exploring glyburide as a potential inhibitor against collagenases.

Effect of dietary antioxidants on the cytostatic effect of acrylamide during copper-deficiency in Saccharomyces cerevisiae.

Acrylamide exposure increases oxidative stress and causes cytotoxicity. In order to understand the role of oxidative stress in acrylamide toxicity, we utilized Saccharomyces cerevisiae as a model organism grown in Yeast Peptone Dextrose (YPD) or Copper-Deficient Medium (CDM). Although the growth curves of yeast were comparable in these media, acrylamide treatment resulted in significant growth inhibition and colony formation only in the CDM.

Advanced glycation end products: role in pathology of diabetic cardiomyopathy.

Increasing evidence demonstrates that advanced glycation end products (AGEs) play a pivotal role in the development and progression of diabetic heart failure, although there are numerous other factors that mediate the disease response. AGEs are generated intra- and extracellularly as a result of chronic hyperglycemia. Then, following the interaction with receptors for advanced glycation end products (RAGEs), a series of events leading to vascular and myocardial damage are elicited and sustained, which include oxidative stress, increased inflammation, and enhanced extracellular matrix accumulation resulting in diastolic and systolic dysfunction.

Attenuation of non-enzymatic thermal glycation of bovine serum albumin (BSA) using β-carotene.

Although heat treatment of proteins is believed to promote and accelerate glycation, the accompanying structural changes in proteins because of heat denaturation and/or glycation are not completely understood. In addition, there is an increasing interest for inhibitors of thermal glycation in food processing. β-Carotene is a naturally occurring carotenoid found in many vegetables, fruits and herbs, with known antioxidant activity.

Copper deprivation modulates CTR1 and CUP1 expression and enhances cisplatin cytotoxicity in Saccharomyces cerevisiae.

Saccharomyces cerevisiae has been established as a model system for cancer studies, due to the widely conserved family of genes involved in cell cycle progression, proliferation and apoptosis. In the current study, we sought to determine whether copper deprivation modulates sensitivity of yeast to cisplatin. Yeast cultures grown in low copper medium and exposed to bathocuproiene disulfate (BCS) resulted in significant reduction of intracellular copper.

Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats.

Objective: Chemotherapeutic agents induce small intestinal mucositis that is characterized structurally by crypt loss and villus atrophy and functionally by absorptive and barrier impairments. We studied the effect of selected individual vitamins and multiple-vitamin mixture supplementation in modulating cisplatin-induced intestinal damage and apoptosis.

Methods: Thirty-six male Wistar/NIN rats 20 wk old and fed the control diet (AIN-93G) were randomly divided into six groups.

Zinc pyrithione salvages reperfusion injury by inhibiting NADPH oxidase activation in cardiomyocytes.

Zinc pyrithione (ZPT), has a strong anti-apoptotic effect when administered just before reperfusion. Because oxidative stress has been proposed to contribute to myocardial reperfusion injury, we tested whether ZPT can reduce the production of reactive oxygen species during reoxygenation in cultured neonatal rat cardiac myocytes and evaluated the role of NADPH oxidase in hypoxia/reoxygenation (H/R) injury. The cells were subjected to 8h of simulated ischemia, followed by either 30 min or 16 h of reoxygenation.

Cardioprotective effect of zinc requires ErbB2 and Akt during hypoxia/reoxygenation.

Recent literature suggests that exogenous zinc can prevent ischemia reperfusion injury by activating phosphoinositide-3 kinase (PI3K)/Akt and by targeting the mitochondrial permeability transition pore (mPTP). It is known that ErbB2 expression promotes association and activation of PI3-kinase/Akt, resulting in growth and survival of cardiac myocytes. In this study, we found that zinc-induced ErbB2 protein expression and Akt activation are required for preventing reperfusion injury.

Chronic low intake of protein or vitamins increases the intestinal epithelial cell apoptosis in Wistar/NIN rats.

Objective: Malnutrition decreases antioxidant defense and increases oxidative stress in the intestine. We studied the effects of long-term restriction of food, protein, and vitamins on intestinal epithelial cell (IEC) apoptosis and the underlying mechanisms.

Methods: Weanling, Wistar/NIN male rats were fed ad libitum with a control diet, 75% protein-restricted diet, or 50% vitamin-restricted diet for 20 wk.