Science, Technology and Medicine open access publisher.Publish, read and share novel research. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice.
Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. Antioxidants in Decelerating Diabetic NephropathyWen-Chin Lee1, 2, Chau-Jong Wang3 and Huei-Jane Lee3[1] Division of Nephrology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan[2] General Education Center, Central Taiwan University of Science and Technology, Taichung, Taiwan[3] Institute of Biochemistry and Biotechnology, Medical College, Chung Shan Medical University, Taichung, Taiwan1.
Chang YC, Huang KX, Huang AC, Ho YC, and Wang CJ2006Hibiscus anthocyanins- rich extract inhibited LDL oxidation and oxLDL-mediated macrophages apoptosis. Chen CC, Hsu JD, Wang SF, Chiang HC, Yang MY, Kao ES, Ho YC, and Wang CJ2003Hibiscus sabdariffaExtract inhibits the development of atherosclerosis in cholesterol-fed rabbits. Chen HC, Guh JY, Chang JM, Hsieh MC, Shin SJ, and Lai YH2005Role of lipid control in diabetic nephropathy.
Tseng TH, Kao TW, Chu CY, Chou FP, Lin WL, and Wang CJ2000Induction of apoptosis Hibiscus protocatechuic acid in human leukemia cells via reduction of retinoblastoma (RB) phosphorylation and Bcl-2 expression.
IntroductionDiabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects of insulin action, insulin secretion or both [1].
IntroductionDiabetes mellitus (DM) is a group of metabolic diseases characterized with inappropriate hyperglycemia due to either a deficiency of insulin secretion or a combination of insulin resistance and inadequate insulin secretion (Masharani, 2008).
Diabetes has taken place as one of the most important diseases worldwide, reaching epidemic proportions. Chopra, 2009Attenuation of diabetic nephropathy by tocotrienol: involvement of NF-KB signaling pathway. Global estimates predict that the proportion of adult population with diabetes will increase 69% for the year 2030 [2].Hyperglycemia in the course of diabetes usually leads to the development of microvascular complications, and diabetic patients are more prone to accelerated atherosclerotic macrovascular disease. Individuals at risk of developing this type of diabetes are found with serologic evidence of an autoimmune process occurring in the pancreatic islets and by genetic markers. These complications account for premature mortality and most of the social and economical burden in the long term of diabetes [3]. In type 2 diabetes, it is a combination of resistance to insulin action and an inadequate compensatory insulin secretion response (American Diabetes Association, 2008).
Increasing evidence suggests that oxidative stress plays a role in the pathogenesis of diabetes mellitus and its complications [4]. Diabetic nephropathy, one of the common complications of diabetes, has become the leading cause of end-stage renal failure in many countries (Chen et al., 2005). Kim, 1997Effects of rebamipide in a model of experimental diabetes and on the synthesis of transforming growth factor-? and fibronectin, and lipid peroxidation induced by high glucose in cultured mesangial cells.
Wolf, 1994Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by activation of transforming growth factor-?.
Hyperglycemia increases oxidative stress, which contributes to the impairment of the main processes that fail during diabetes, insulin action and insulin secretion. In general, about 1 out of 3 patients with type 1 or type 2 diabetes proceed to developing significant diabetic nephropathy (Zipp and Schelling, 2003). Ziyadeh, 1992High glucose- induced proliferation in mesangial cells is reversed by autocrine TGF-?. In addition, antioxidant mechanisms are diminished in diabetic patients, which may further augment oxidative stress [5, 6].
It is believed that the pathophysiologic mechanisms of renal disorder are similar in both types of diabetes (Kern et al., 1999). Zhao, 2006Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-KB-dependent down-regulation of vascular cell adhesion molecule-1 expression. Abboud, 1997Expression of transforming growth factor-? and type IV collagen in early streptozotocin- induced diabetes.
Border, 1993Expression of transforming growth factor-? is elevated in human and experimental diabetic nephropathy. The pathogenesis and clinical course of diabetic nephropathy can be monitored by structural and hemodynamic changes. Brownlee, 2003Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells.
Lee, 2002Role of high glucose-induced nuclear factor-KB activation in monocyte chemoattractant protein-I expression by mesangial cells.
1 The Haber-Weiss and Fenton reactions combine using poorly liganded iron in a catalytic cycle to produce the very damaging hydroxyl radical. Oxidative stress At the beginning of life, the organisms obtained their energy (ATP) by anoxygenic photosinthesis, for which oxygen was toxic. The earliest changes is an increase in glomerular filtration rate (GFR), also call “hyperfiltration” stage, which is followed by detectable glomerular lesions with normal albumin excretion rate. Poorly liganded iron can also be liberated via the destruction of haem and other iron-containing substances. Most of the metabolic pathways were developed during this anaerobic stage of life, in which oxygen came later.
Makino, 2003HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effects in rats.

Cyanobacteria started producing oxygen from photosynthesis, which raised the atmospheric oxygen, and favored those organisms which have evolved into eukaryotic cells with mitochondria, able to use oxygen for a more efficient energy production [9].Whenever a cell’s internal environment is perturbed by infections, disease, toxins or nutritional imbalance, mitochondria diverts electron flow away from itself, forming reactive oxygen species (ROS) and reactive nitrogen species (RNS), thus lowering oxygen consumption. Once microalbuminuria persist, both changes in glomerular structure, such as mesangial expansion and basement membrane thickening, and permeability happened, which is referred as “incipient nephropathy”.
Pitha, 1999The kidney in metabolic disorder-- diabetes mellitus, hyperuricemia, oxalosis, nephrocalcinosis, and nephrolithiasis. This “oxidative shielding” acts as a defense mechanism for either decreasing cellular uptake of toxic pathogens or chemicals from the environment, or to kill the cell by apoptosis and thus avoid the spreading to neighboring cells [9]. Diabetic subjects with persistent microalbuminuria are at increased risk for “overt diabetic nephropathy”. Kasuga, 2007Overexpression of thioredoxin1 in transgenic mice suppresses development of diabetic nephropathy. Lee, 2005Reactive oxygen species mediate high glucose-induced plasminogen activator inhibitor-1 upregulation in mesangial cells and in diabetic kidney. Jerums, ME Copper, 2001Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE).
Weisberg, 1997Increased renal production of transforming growth factor-beta 1 in patients with type II diabetes.
The term “oxidative stress” has been used to define a state in which ROS and RNS reach excessive levels, either by excess production or insufficient removal. Being highly reactive molecules, the pathological consequence of ROS and RNS excess is damage to proteins, lipids and DNA [10].
After several years of persistent proteinuria, progression to end-stage renal disease will occur (Caramori and Mauer, 2001). Consistent with the primary role of ROS and RNS formation, this oxidative stress damage may lead to physiological dysfunction, cell death, pathologies such as diabetes and cancer, and aging of the organism [11].
An increase in serum GGT is thought to be an early and sensitive marker of oxidative stress. Chan, 2007Catalase overexpression attenuates angiotensinogen expression and apoptosis in diabetic mice.
Linear regression analysis revealed AD was an independent correlate of elevated GGT levels.
Histochemical detection of iron in AD (A) compared with control cases (B) show striking association of iron with neurofibrillary tangles (arrowheads) and senile plaques (arrows) characteristic of the AD brain.
Based of their analyses, the authors stated, "We argue that high ferritin levels may contribute to an accelerated pathology in AD. But seen in the context of arresting apoptosis, HO-1 and tau may play a role in maintaining the neurons free from the apoptotic signal (cytochrome c), since tau has strong iron-binding sites. The sources of ROS-mediated damage appear to be multi-faceted in AD, with interactions between abnormal mitochondria, redox transition metals, and other factors. Interestingly, glial accumulations of redox-active iron in the cerebellum were also evident in preclinical AD patients and tended to increase as patients became progressively cognitively impaired.
Therefore, progress in the areas of prevention and disease modification may be of critical interest. In this review, we summarize novel AD therapeutics that are currently being explored, and also mechanisms of action of specific drugs within the context of current knowledge of AD pathologic pathways.
Free cationic iron is a potent pro-oxidant and can initiate a set of reactions that form extremely reactive products, such as OH. Mn can oxidize dopamine (DA), generating reactive species and also affect mitochondrial function, leading to accumulation of metabolites and culminating with OS. The researchers first noted, "Gamma glutamyltransferase (GGT) plays a role in cellular glutathione uptake, which is an important element of antioxidant mechanisms.
For cognitive assessment, MMSE and clock drawing tests were performed; DSM-IV and NINCDS-ADRDA criteria were used. Hypertension, diabetes mellitus, total cholesterol, and low density lipoprotein cholesterol were not associated with GGT levels.
Current alcohol intake and lifetime alcohol intake were determined by self-report measures. The link with GGT may reflect that elevated GGT levels are a sign of increased oxidative stress.
The investigators noted, "Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. Gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission.
Magnetic resonance imaging examination was conducted in both groups (after 3-week abstinence in the patient group). Age and sex were significantly correlated with some BV measurements in both patient and control groups.
In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients.
We assessed 3 WM and 5 gray matter regions in 39 postmenopausal women, of whom 15 had premenopausal hysterectomy, utilizing a validated magnetic resonance imaging technique called field-dependent R2 increase (FDRI) that quantifies ferritin iron. Men had higher iron levels than women without hysterectomy in 3 brain regions but did not differ from women with hysterectomy in any region. The subjects were compared to 56 matched healthy controls and 28 Huntington's disease gene carriers.

Abnormal iron utilization by mitochondria, as has been proposed in Friedreich's ataxia, is another possible mechanism of iron accumulation.
Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. Free Iron (Fe2+) reacts trough the Fenton reaction with hydrogen peroxide, leading to the generation of very reactive and damaging hydroxyl radicals (OH•). Superoxide can also react with ferric iron in the Haber-Weiss reaction leading to the production of Fe2+, which then again affects redox cycling.
The highly reactive hydroxyl radicals lead to oxidative stress-induced lipid peroxidation, mitochondrial dysfunction, and increase in intracellular free-calcium concentration, and finally causing neuronal deathIron deposition and inflammation in multiple sclerosis. Our study focused on non-heme iron distribution and the expression of the iron-related proteins ferritin, hephaestin and ceruloplasmin in relation to oxidative damage in the brain tissue of 33 MS and 30 control cases.
In chronic MS, however, there was a significant decrease of iron in the normal appearing white matter (NAWM) with disease duration, when corrected for age.
At lesion edges and within centers of lesions, iron accumulated in astrocytes and axons. They observed a significant positive relationship between brain iron and age and that women had significantly lower ferritin iron than men in five regions. Men with the common hemochromatosis genotypes had significant higher brain iron content that the other men. Putative pathway sources for iron release, such as ferritin, neuromelanin (NM) or neurotoxins. Neurotoxins, such as MPTP, kainate, 6-hydroxydopamine (6-OHDA) can mediate release of iron. Subsequently, this reactive-free iron may react via the Fenton reaction with the hydrogen peroxide produced from example monoamine oxidase metabolised dopamine, to yield toxic and hydroxyl (OH·) free radical species.
These highly reactive OH· radicals may orchestrate a cascade of cellular deleterious events such as oxidative stress. Finally, oxidative stress may disturb the cellular calcium homeostasis, thereby resulting in excitotoxicity and finally apoptoticinduced cell death. The elevated iron levels in the substantia nigra may thus play an instrumental role in the vulnerability and degeneration of this area, which is characteristic to Parkinson’s disease. Elevated levels of the metal have been found in the brains of patients of numerous neurodegenerative disorders, including Parkinson's disease (PD).
The pathogenesis of PD is largely unknown, although it is thought through studies with experimental models that oxidative stress and dysfunction of brain iron homeostasis, usually a tightly regulated process, play significant roles in the death of dopaminergic neurons.
Accumulation of iron is present at affected neurons and associated microglia in the substantia nigra of PD patients.
This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation of α-synuclein protein, and exacerbate or even cause neurodegeneration.
There are various treatments aimed at reversing this pathologic increase in iron content, comprising both synthetic and natural iron chelators.
These include established drugs, which have been used to treat other disorders related to iron accumulation. We assessed dietary iron intake with a semiquantitative food-frequency questionnaire in 104 PD patients and 352 control subjects, frequency matched for age and gender.
The researchers concluded, "The results suggest that in specific subgroups of healthy older individuals, higher accumulations of iron in vulnerable gray matter regions may adversely impact memory functions and could represent a risk factor for accelerated cognitive decline. Recently, many studies demonstrated that pre-diabetes, MetS, and T2DM are risk factors in the development of AD and have many common mechanisms. This property, while essential for its metabolic functions, makes iron potentially hazardous. Methods: The plasma albumin, uric acid, GGT and IMA levels were measured by spectrophotometric methods in 32 AD patients and 32 healthy controls.
The Mini Mental Status Examination and Clinical Dementia Rating Scale were used to evaluate the cognitive functions of AD patients. Results: AD patients had significantly higher IMA levels as compared to those of the controls respectively.
Uric acid concentrations were significantly decreased and GGT values were significantly increased in AD when compared with control group. Albumin levels of the patients were also compared and no significant difference was detected. Redox cycling between ferrous and ferric iron is utilized in biology for various electron transfer reactions essential to life, yet this same chemistry mediates deleterious reactions with oxygen that induce oxidative stress. Consequently, there is a precise and tightly controlled mechanism to regulate iron in the brain. When iron is dysregulated, both conditions of iron overload and iron deficiencies are harmful to the brain.

High blood sugar low sodium recipes
Normal blood sugar level for type 1 diabetics
What should your blood sugar be after eating a meal g?revi


  1. 10.11.2015 at 14:57:40

    Dips too low and I get was made by the Israel Defense.

    Author: SHEMKIREC_057
  2. 10.11.2015 at 11:43:39

    Into the body and 29% of adults are affected by DM2 and that the liver plays.

    Author: Bratan