Search

Introduction: The gastrointestinal tract is frequently exposed to noxious stimuli that may cause oxidative stress, inflammation and injury. Intraluminal pro-oxidants from ingested nutrients especially iron salts and ascorbic acid frequently consumed together, can lead to catalytic formation of oxygen-derived free radicals that ultimately overwhelm the cellular antioxidant defense and lead to cell damage., Hypothesis: Since the mechanisms remain sketchy, efforts have been exerted to evaluate the role of epigenetics in modulating components of endogenous enzymatic antioxidants in the intestine. To this end, Caco-2/15 cells were exposed to the iron-ascorbate oxygen radical-generating system., Results: Fe/Asc induced a significant increase in lipid peroxidation as reflected by the elevated formation of malondialdehyde along with the alteration of antioxidant defense as evidenced by raised superoxide dismutase 2 (SOD2) and diminished glutathione peroxidase (GPx) activities and genes. Consequently, there was an up-regulation of inflammatory processes illustrated by the activation of NF-κB transcription factor, the higher production of interleukin-6 and cycloxygenase-2 as well as the decrease of IκB. Assessment of promoter's methylation revealed decreased levels for SOD2 and increased degree for GPx2. On the other hand, pre-incubation of Caco-2/15 cells with 5-Aza-2'-deoxycytidine, a demethylating agent, or Trolox antioxidant normalized the activities of SOD2 and GPx, reduced lipid peroxidation and prevented inflammation., Conclusion: Redox and inflammatory modifications in response to Fe/Asc -mediated lipid peroxidation may implicate epigenetic methylation.

It was studied that type 2 diabetes mellitus is connected with increased plasma lipid peroxidation (lipid peroxidation expressed as malondialdehyde). This review aimed to evaluate the state of lipid peroxidation among type 2 diabetic subjects. Present finding showed that lipid peroxidation increased in type 2 diabetes mellitus. Increased lipid peroxidation maybe is associated with some diseases such as cancer, cardiovascular diseases and diabetes mellitus. Lipid peroxidation has an important role in the pathogenesis and the complications of diabetes. Antioxidants have been found to prevent the progression and occurrence of diabetes. There are several mechanisms that may cause lipid peroxidation affront in diabetic subjects, although, their precise contributions are not completely clear. We proposed that production of free radicals can be reduced by preventing high blood glucose levels and by the control of instabilities in blood glucose levels. A contributor to these instabilities in blood glucose is glycaemic control by using of fast blood sugar test. Furthermore, the earlier assessment of the advancement of diabetes that firmly control of blood glucose can be obtained; the greater will be the decrease in diabetic complications. Patients with type 2 diabetes may have very high physiological antioxidants requirements.

Pro-oxidants, reactive species and free radicals, are toxic substances that can cause oxidative damage to major constituents of biological systems. In contradistinction, antioxidants are defined as any substance that significantly prevents the pro-oxidant-initiated oxidation of a substrate. Consequently, it was suggested that it might be possible to reduce free radical damage and thus cancer risk through 3 dietary changes: (1) caloric reduction, that is, lowering the level of free radical reactions arising in the course of normal metabolism; (2) minimize dietary components that increase the level of free radical reactions (eg, polyunsaturated fats); and (3) supplement the diet with one or more free radical reaction inhibitors (antioxidants). Lipid peroxidation exemplifies the type of chain reaction initiated by free radicals in (2) and (3). Both the phenolic antioxidant butylated hydroxytoluene (BHT) and the carotenoid beta-carotene can terminate such reactions and have been shown to influence ultraviolet (UV) carcinogenesis. However, there is a lack of correlation between physicochemical and patho-physiological responses in both instances. Whereas the influence on UV carcinogenesis of both antioxidants has been reported to diminish as the level of dietary fat decreases, pointing to the involvement of lipid peroxidative reactions, the mode of BHT's action in inhibiting UV carcinogenesis appears to be related to UV dose diminution through increased spectral absorbance of the stratum corneum. beta-carotene has no such effect and may actually exacerbate UV carcinogenesis under certain dietary conditions. This paradox points to the complex relationship between chemical mechanisms and biological mode of action of antioxidants. Recent clinical and experimental data suggest that antioxidant supplementation of the complex and intricately balanced natural antioxidant defense system as a cancer prevention strategy will demand extreme caution.

Free radicals and related species have attracted a great deal of attention in recent years. They are mainly derived from oxygen (reactive oxygen species/ROS) and nitrogen (reactive nitrogen species/RNS), and are generated in our body by various endogenous systems, exposure to different physicochemical conditions or pathophysiological states. Free radicals can adversely alter lipids, proteins and DNA and have been implicated in aging and a number of human diseases. Lipids are highly prone to free radical damage resulting in lipid peroxidation that can lead to adverse alterations. Free radical damage to protein can result in loss of enzyme activity. Damage caused to DNA, can result in mutagenesis and carcinogenesis. Redox signaling is a major area of free radical research that is attracting attention. Nature has endowed us with protective antioxidant mechanisms- superoxide dismutase (SOD), catalase, glutathione, glutathione peroxidases and reductase, vitamin E (tocopherols and tocotrienols), vitamin C etc., apart from many dietary components. There are epidemiological evidences correlating higher intake of components/ foods with antioxidant abilities to lower incidence of various human morbidities or mortalities. Current research reveals the different potential applications of antioxidant/free radical manipulations in prevention or control of disease. Natural products from dietary components such as Indian spices and medicinal plants are known to possess antioxidant activity. Newer and future approaches include gene therapy to produce more antioxidants in the body, genetically engineered plant products with higher level of antioxidants, synthetic antioxidant enzymes (SOD mimics), novel biomolecules and the use of functional foods enriched with antioxidants.

Unlabelled: Adriamycin (ADR), which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in many organs. The present study was designed to investigate the effect of lipoic acid (LA) against acute ADR induced peroxidative damages in rat kidney. The study was carried out with adult male albino rats of Wistar strain, which comprised of one control and three experimental groups. Group I rats served as controls. Group II rats received ADR (7.5mg/kg body weight) intravenously through the tail vein. Group III rats were given LA (75 mg/kg body weight) intraperitoneally. Group IV rats were given LA one day before the administration of ADR. Rats subjected to ADR administration showed a decline in the thiol capacity of the cell accompanied by high malondialdehyde (MDA) levels along with lowered activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) glutathione (GSH) and GSH metabolizing enzymes (glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD)). However no significant change was observed in the activity of glutathione-S-transferees (GST). Pretreatment with LA showed considerable changes over oxidative stress parameters. Nephrotoxic damage was evident from the decrease in the activities of gamma-glutamyl transferase (gamma-GT) and beta-glucuronidase (beta-GLU), which were reverted upon LA pretreatment., Conclusion: This study has highlighted the beneficial effects of LA pretreatment in reversing the damages caused by ADR, by bringing about an improvement in the reductive status of the cell.

We conducted a study of lipid peroxidation as a marker of age-related free-radical damage in the human larynx--the first study of its kind. A colorimetric assay for malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) was performed on extracts taken from thyroarytenoid muscle harvested from fresh cadaveric laryngeal specimens. Levels of MDA and 4-HNE were measured by spectrophotometry. Correlation studies were performed by linear regression analysis. We found that MDA levels in human thyroarytenoid muscle appeared to increase with age while 4-HNE levels showed a slight decrease with age. Our findings are consistent with those of previous studies of other organ systems and indicate that there is a need for further study of free-radical damage and the effects of aging on the human larynx and on voice production.

Objective: To investigate the inhibitory effects of tea polyphenols (TP) and Vitamin C (Vit C) on FeSO4-cysteine induced lipid peroxidation in isolated human plasma and carbon tetrachloride (CCl4) induced liver free radical injury in mice., Method: The experiment included two parts: (1) In FeSO4-cysteine induced lipid peroxidation system of isolated human plasma, malondialdehyde (MDA) content was detected after administration of different concentrations of TP (0.3 ~ 8.1 mg/L, as C ~ F group) and Vit C (3 ~ 81 mg/L, as G ~ J group) respectively; (2) Thirty-six male Kunming mice were randomly divided into four groups: control group (A), CCl4 damage group (B), TP protection group (C) and Vit C protection group (D). TP or Vit C (100 mg/kg) was given orally to group C and D respectively, while the same volume of distilled water was given to the other two groups one time every day, continued for three days. Twelve hours after the final treatment, CCl4 (230 mg/kg) was given orally to group B ~ D. Thirty six hours later, all the mice were decapitated and liver homogenate were prepared for measuring MDA content., Result: In FeSO4-cysteine induced lipid peroxidation in isolated human plasma, the inhibitory rate of TP (0.3 ~ 8.1 mg/L) was 30.7%, 32.0%, 46.9% and 59.7 %, and the inhibitory rate of Vit C (3 ~ 8.1 mg/L) was 8.3%, 41.4%, 47.7% and 52.7% for various dosages. In the CCl4 induced liver free radical injury system, the inhibitory rate of the same dosage of TP and Vit C was 45.2%, 42.8% respectively., Conclusion: TP (0.3 ~ 8.1 mg/L) and Vit C (9 ~ 81 mg/L) had inhibited lipid peroxidation induced by FeSO4-cysteine in isolated human plasma significantly, and the inhibitory effects of TP was superior to that of Vit C at the same dosages. The same dosage of TP and Vit C had remarkable inhibitory effects on the CCl4 induced liver free radical injury, but there was no significant difference between the two groups.

A novel family of prostaglandin F2 isomers, called F2-isoprostanes, produced in large quantities in vivo by a free radical peroxidation of arachidonic acid, has recently been described. The quantification of the two major isoforms (isoprostaglandin F2alpha type-III and VI) in biological fluids and tissues as markers of lipid peroxidation appears to be an important advance in our ability to explore the role of free radicals in the pathogenesis of human disease. In addition, F2-isoporstanes quantification seems promising as intermediate endpoints for clinical studies of antioxidant therapies.

Aim: To test the hypothesis that complications of neonatal intensive care are related to increased oxygen derived free radical activity, using breath pentane as a marker of lipid peroxidation., Methods: Exhaled breath was collected daily from 57 ventilated preterm infants and pentane concentration measured by gas chromatography., Results: High peak pentane exhalation was significantly associated with low gestational age, mortality, intraventricular haemorrhage and retinopathy of prematurity. Peak pentane was not significantly associated with the development of chronic lung disease., Conclusions: The demonstration that pentane exhalation is related to the course of neonatal disease and its outcome is consistent with the hypothesis that lipid peroxidation is associated with these illnesses, and may contribute to their severity. If this is a causal relation, antioxidant treatments could prove useful in reducing their severity. Measurement of breath pentane might assist in the assessment of antioxidant strategies prior to more extensive clinical trials.

Reactive oxygen species derived from molecular oxygen are highly reactive metabolites. These species can be generated by cellular or acellular mechanisms. They react with all biological molecules such as protein, lipid, and carbohydrates. The reaction of these species with lipids, called lipid peroxidation, is a very well-studied phenomenon. Compounds, which scavenge these molecules, are called antioxidants. The disruption of the delicate balance between pro- and antioxidants has been implicated in the pathophysiology of many chronic diseases such as, for example, atherosclerosis. This article presents an introduction to what reactive oxygen species are and their reactions with various metabolites. It deals with lipid peroxidation in detail and with methods for measuring lipid peroxidation. This article also outlines the importance of these species in the pathology of various gynecological diseases.

The effect of different doses of methylglyoxal (50-400 mg/kg body wt.) were examined using enzymes involved in the antioxidant function, glutathione (GSH) content and lipid peroxidation in the liver and spleen of Swiss albino mice (7-8 week old) after 6, 12 and 24 h. Significant changes were observed predominantly in the liver. The specific activities of superoxide dismutase (SOD), glutathione-S-transferase (GST), catalase, glyoxalase I (gly I) and glyoxalase II (gly II) were found to decrease in the liver. The mode and magnitude of change in the specific activities was seen to depend on the dose of methylglyoxal and the time after its administration. Methylglyoxal also decreased the GSH content and enhanced the lipid peroxidation in the liver. These findings are suggestive of the adverse effect of methylglyoxal on the antioxidant defence system. It is likely that methylglyoxal undergoes a redox cycle and generates the free radicals which in turn lower the antioxidant status in animals. The increased levels of lipid peroxidation provide support for the involvement of free radical processes in the detrimental effects of methylglyoxal. The response of DT-diaphorase (DTD) seems to be adaptive.

Objectives: Although Alzheimer's disease (AD) is the leading cause of dementia in developed countries, there is an as yet unexplained lower prevalence of the disease in parts of Africa. AD is characterised by a catastrophic loss of neurons; free radicals (oxidative toxins) have been implicated in the destruction of the cells through the process of lipid peroxidative damage of cell membranes. Previously aluminium (Al) and a fragment of beta amyloid (A beta 25-35) were shown to exacerbate free-radical damage, while melatonin reduced this effect. The aim of the present study was: (i) to investigate the conditions determining the toxicity of Al and A beta 25-35; and (ii) to assess whether melatonin could attenuate the damage done by both aluminium and the amyloid fragment, thus suggesting a pathway for the aetiology of AD., Design: An in vitro model system was used in which free radicals were generated, causing lipid peroxidation of platelet membranes, thus simulating the disease process found in the brain., Results: 1. Al and A beta 25-35 caused lipid peroxidation in the presence of the iron (II) ion (Pe2+), Al being more toxic than A beta 25-35. 2. A beta 25-35 attenuated the lipid peroxidation promoted by Al. 3. Hydrogen peroxide (H2O2) greatly exacerbated the toxicity of Al and A beta 25-35. 4. Melatonin prevented lipid peroxidation by Al and A beta 25-35 in the absence of H2O2, but only reduced the process when H2O2 was present., Conclusions: In the light of the results obtained from the present study, the following hypotheses are formulated. 1. In AD, excessive quantities of Al are taken up into the brain, where the Al exacerbates iron-induced lipid peroxidation in the lysosomes. 2. In response, the normal synthetic pathway of amyloid protein is altered to produce A beta fragments which attenuate the toxicity of Al. In the process of sequestering the Al and iron, immature plaques are formed in the brain. 3. Microglia are activated, in an attempt to destroy the plaques by secreting reactive oxygen species such as H2O2. At this point in the disease process, lipid peroxidation causes a catastrophic loss of brain cells. 4. Melatonin, together with other free radical scavengers in the brain, reduces the free-radical damage caused by Al and A beta, except in the latter stages of the disease process. Since melatonin is produced by the pineal gland only in the dark, the excess of electric light in developed countries may help explain why AD is more prevalent in these countries than in rural Africa.

To evaluate the age-related response of essential cell functions against peroxidative damage in hyperthermia, we studied the biochemical response to heat stress in both young and aged rats. Passive hyperthermia was immediately observed in rats after exposure to hot environments. In aged rats, the rectal temperature maintained thermal homeostasis and increased to the same degree as in young rats. In these aged animals, the damage from heat stress was more serious than in young animals. In aged rats under normal environmental conditions, hepatic cytosolic glutathione peroxidase (GSH peroxidase) activities were markedly higher than those activities in younger rats. Hepatic cytosolic GSH peroxidase activities were induced by heat stress in young rats but were decreased by hot environments in aged rats. Hepatic catalase activities in young rats were not affected by hot environments, whereas in aged rats, hepatic catalase activities were seriously decreased. Catalase activities in the kidney of aged rats were also reduced by hot environments. Lipid peroxidation in the liver was markedly induced in both young and aged rats. Because the protective enzymes for oxygen radicals in aged rats were decreased by hot environments, lipid peroxidation in the liver was highly induced. In aged rats, lipid peroxidation in intracellular structures such as mitochondria and microsomes was also markedly induced by hot environments. In both young and aged rats, hyperthermia greatly increased the development of hypertrophy and vacuolated degeneration in hepatic cells. In aged rats, both mitochondria and endoplasmic reticulum of the hepatic cells showed serious distortion in shape as a result of exposures to hot environments. Microsomal electron transport systems, such as cytochrome P450 monooxygenase activities, were seriously decreased by heat stress in aged rats but not in young rats. Although the mitochondrial electron transport systems were not affected by acute heat stress in young rats, their activities were simultaneously inhibited after long-lasting heat exposure. In isolated hepatic cells and polymorphonuclear leukocytes in animals, the 70-kDa heat shock-induced proteins were markedly increased by heat stress. In conclusion, the heat stress-inducible oxygen radical damage becomes more severe according to the age of rats. Because aging and hyperthermia have a synergistic effect on lipid peroxidation, protective enzyme activities for oxygen radicals may be essential for surviving and recovering from thermal injury in aged animals and also in humans.

Using an electron spin resonance technique, free radical signals were observed to be increased in liver of rats 15, 30 and 45 min after orally dosing with 80 mg/kg 3-nitropropionic acid (3-NPA). Concentrations of 3-NPA from 595 to 2380 mg/litre enhanced the formation of adrenochrome from adrenaline in mitochondria and microsome suspensions of liver and brain. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) as well as the content of malonidialdehyde (MDA) were significantly increased in liver of rats dosed with 80 mg/kg 3-NPA. There was also a cerebral increase of activity of SOD and content of MDA. These results suggest that 3-NPA is able to produce lipid peroxidation both in vivo and in vitro.

Lipid peroxidation is considered at present as one of the basic mechanisms involved in reversible and irreversible cell and tissue damage. The current knowledge about the role of peroxidative breakdown of polyunsaturated fatty acids in the pathogenesis of various diseases has been reviewed. Lipid peroxidation leads to degradation of the lipid membrane, interaction of degradation products with intra- and extracellular targets and to the production of new reactive oxygen species during the course of the chain reaction thus leading to damage of cells and tissues. According to our current view lipid peroxidation is implicated in the pathogenesis of cancer, inflammatory processes, atherosclerosis, toxic injury by xenobiotics and ischemic-reperfusion damage.

A naso-orbital injury is often associated with a craniocerebral injury due to the close anatomical localization of the facial and cerebral compartments of the skull. Patients with such injuries showed enhancement of free-radical lipid oxidation and microcirculation disorders. They were controlled by traditional therapeutic methods in combination with antioxidants of direct and indirect action (ascorbic acid, flacumin, alpha-tocopherol acetate, pentoxifylline ) that were given in standard doses. Improvement of microcirculation and decrease of free-radical oxidation of lipids were followed by faster normalization of bioelectric activity and hemodynamics of the brain and earlier clinical recovery. Microcirculation parameters recorded during biomicroscopy of vessels of the bulbar conjunctiva can be used for evaluating cerebral circulation because vessel responses of the eyeball and the brain are similar.