Formation Of Lipid Peroxidation Products Research Articles

The link between intraneuronal N-truncated amyloid-β peptide and oxidatively modified lipids in idiopathic autism and dup(15q11.2-q13)/autism

BackgroundAutism is a neurodevelopmental disorder of unknown etiopathogenesis associated with structural and functional abnormalities of neurons and increased formation of reactive oxygen species. Our previous study revealed enhanced accumulation of amino-terminally truncated amyloid-β (Aβ) in brain neurons and glia in children and adults with autism. Verification of the hypothesis that intraneuronal Aβ may cause oxidative stress was the aim of this study.ResultsThe relationships between neuronal Aβ and oxidative stress markers—4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)—were examined in the frontal cortex from individuals aged 7–32 years with idiopathic autism or with chromosome 15q11.2-q13 duplications (dup(15)) with autism, and age-matched controls. Quantification of confocal microscopy images revealed significantly higher levels of neuronal N-truncated Aβ and HNE and MDA in idiopathic autism and dup(15)/autism than in controls. Lipid peroxidation products were detected in all mitochondria and lipofuscin deposits, in numerous autophagic vacuoles and lysosomes, and in less than 5% of synapses. Neuronal Aβ was co-localized with HNE and MDA, and increased Aβ levels correlated with higher levels of HNE and MDA.ConclusionsThe results suggest a self-enhancing pathological process in autism that is initiated by intraneuronal deposition of N-truncated Aβ in childhood. The cascade of events includes altered APP metabolism and abnormal intracellular accumulation of N-terminally truncated Aβ which is a source of reactive oxygen species, which in turn increase the formation of lipid peroxidation products. The latter enhance Aβ deposition and sustain the cascade of changes contributing to metabolic and functional impairments of neurons in autism of an unknown etiology and caused by chromosome 15q11.2-q13 duplication.

Protective effects of osthole against myocardial ischemia/reperfusion injury in rats

Osthole, a bioactive simple coumarin derivative extracted from a number of medicinal plants, such as Cnidium monnieri and Angelica pubescens, has been shown to exert a variety of pharmacological activities and is considered to have potential therapeutic applications. In this study, we investigated the protective effects of osthole against myocardial ischemia/reperfusion (I/R) injury in rats. Male Sprague-Dawley rats were randomly assigned to 1 of 5 groups: the sham-oeprated control group (control), the vehicle group (vehicle), and 3 treatment groups, which were treated with osthole at the concentration of 1, 10 or 50 mg/kg (intraperitoneally), respectively, upon the initiation of myocardial ischemia. Treatment with osthole suppressed the formation of lipid peroxidation products, enhanced the capacities of antioxidant enzymes and inhibited the expression of inflammatory cytokines following myocardial I/R injury. Moreover, treatment with osthole reduced high-mobility group box protein 1 (HMGB1) and phosphorylated nuclear factor (NF)-κB expression in ischemic myocardial tissue. These results demonstrate the protective effects of osthole against myocardial I/R injury in rats and suggest that these effects may be associated with its antioxidant and anti-inflammatory activities.

Bleaching augments lipid peroxidation products in pistachio oil and its cytotoxicity

Pistachio consumption is associated with reductions in serum cholesterol and oxidative stress due to their constituents of unsaturated fats, phytosterols, fiber, and antioxidants. Bleaching has been applied to whiten nut shells for antifungal and cosmetic purposes. However, the impact of bleaching on nutritional quality and safety of pistachios remains to be examined. In this study, we investigated whether bleaching would increase malondialdehyde (MDA) or 7-keto-sitosterol and decrease phytosterols in pistachio oil, as well as cause cytotoxicity of modeled Hepa1c1c7 cells. Bleached pistachio oil had larger than 12.6% decrease in b-sitosterol and total phytosterols as compared to the raw oil (P � 0.05). Bleaching with Fe 2þ significantly increase 7-keto-sitosterol compared to bleaching alone. Hepatic cell viability was decreased the most by the oil of the pistachios treated with bleach containing Fe 2þ (P � 0.05), and lactate dehydrogenase activity in medium was elevated by >18-folds (P � 0.05). Compared to natural pistachios, the bleaching treatment had detrimental effects on nutritional quality and expected health benefits of pistachios by increasing lipid peroxidation, decreasing phytosterol content, and causing cytotoxicity. Practical applications: Bleaching has been applied to whiten the nut shell for antifungal and cosmetic purposes. However, the results of this study indicate that bleaching treatment has a detrimental impact on nutritional quality and expected health benefits of pistachios. Particularly, treatment with a bleach formula with hydrogen peroxide and transit metals increases formation of lipid peroxidation products and decreases phytosterol content. The resulting pistachio oil causes cell toxicity. Thus, bleaching practice for whitening pistachios is strongly discouraged.

A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates liver fibrosis induced by porcine serum in rats

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. This study was carried out to investigate the effects of PAE on liver fibrosis induced by porcine serum (PS) in rats and to explore its possible mechanisms. Liver fibrosis was induced in male Wistar rats by injection with PS intraperitoneally. The rats were randomly divided into a normal control group, a liver fibrosis model group and a PAE (40, 80, 160 mg•kg-1) treated group. After a 16-week treatment, PAE-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis upon pathological examination. Administration of PAE significantly decreased serum HA, PC III levels, and content of hydroxyproline in the liver tissue of fibrotic rats. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during PS treatment. In vitro, PAE also significantly decreased [3H]-thymidine incorporation in hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB). Moreover, PAE significantly decreased the expression of PDGF receptor beta (PDGFR-β) and p-ERK1/2, p-p38, p-JNK. The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of liver fibrosis.

Synergism between paraoxonase Arg 192 and the angiotensin converting enzyme D allele is associated with severity of coronary artery disease

Toxicity due to excess fluoride concentration in drinking water is of great concern in people who rely only on the ground water as their water source in many region of the world.We collected samples and examined the toxicity of fluoride in a population residing at Salem, Dharmapuri and Krishnagiri districts of Tamil Nadu, India and measured HDL bound enzyme (PON1), erythrocyte membrane bound enzymes (acetylcholinesterase, AChE) and adenosine 5′ triphosphatase (ATPases), plasma enzyme (butyrylcholinesterase, BChE) and rate limiting enzyme in heme biosynthesis (delta aminolevulinic acid dehydratase, δ-ALAD) activities.In fluorosis patients, formation of lipid peroxidation product was more in erythrocytes than in plasma. The observation further revealed that there was 50% reduction in the activity of HDL bound anti atherogenic enzyme-paraoxonase (PON1). The activities of membrane bound and signaling enzymes (acetylcholinesterase - AChE and adenosine 5′ triphosphatase - ATPase) of erythrocyte were also diminished. These results suggested that there was defectiveness in the signaling and energy metabolism in fluorosis patients. Altered isoenzyme pattern of lactate dehydrogenase (LDH) in fluorosis samples was observed. Furthermore, the result suggested that both the heart (LDH 1) and liver (LDH 5) were most affected by fluoride toxicity. The study also provided reference values for tests which are used to predict the severity of fluoride toxicity.The toxic effect of fluoride was due to the collective effects on vital protective system rather than single factor.

Purple Rice Berry Is Neuroprotective and Enhances Cognition in a Rat Model of Alzheimer's Disease

Alzheimer's disease, a neurodegenerative disease characterized by progressive memory loss and cognitive impairment, is the most common type of dementia in aging populations due to severe loss of cholinergic neurons in a specific area. Oxidative stress is known to be involved in the pathogenesis of this condition. Therefore, the cognition-enhancing and neuroprotective effects of rice berry (Oryza sativa), a purple-pigmented rice that is rich in antioxidant substances, was evaluated. Young adult male Wistar rats, weighing 180-220 g, were orally given rice berry once daily at doses of 180, 360, and 720 mg/kg of body weight for a period of 2 weeks before and 1 week after the induction of memory deficit and cholinergic lesions with AF64A, a specific cholinotoxin, via bilateral intracerebroventricular administration. One week following AF64A administration the rats were evaluated for spatial memory, neuron density, acetylcholinesterase activity, and hippocampal lipid peroxidation products. Our results showed that rice berry could significantly prevent memory impairment and hippocampal neurodegeneration in hippocampus. Moreover, it also decreased hippocampal acetylcholinesterase activity and lipid peroxidation product formation. These results suggest that rice berry has potential as an effective agent for neurodegeneration and memory impairment in Alzheimer's disease.

Effects and Mechanisms ofAcremoniumterricola milleretal myceliumon Liver Fibrosis Induced by Carbon Tetrachloride in Rats

Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride (CCl(4)) and explore its possible mechanisms. The animal model was established by injection with 50% CCl(4) subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl(4)-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl(4) treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl(4), and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.

Effect of Isoproterenol on Tissue Defense Enzymes, Hemodynamic and Left Ventricular Contractile Function in Rats

Present study investigated the effects of isoproterenol-induced oxidative stress on hemodynamic and ventricular functions in rats. Subcutaneous injections of isoproterenol (85mg/kg for two consecutive days at 24h interval) significantly decreased myocardial antioxidant enzymes; superoxide dismutase, catalase and glutathione peroxidase in heart. Isoproterenol-induced oxidative stress was also evidenced by significant depletion of reduced glutathione and increased formation of lipid peroxidation product, thiobarbituric acid reactive substances along with depletion of myocyte injury specific marker enzymes; creatine phosphokinase isoenzyme and lactate dehydrogenase. The deleterious outcome of oxidative stress on hemodyanmic parameters and ventricular function were further evidenced by decreased systolic, diastolic and mean arterial blood pressure, heart rate, ventricular contractility; [(+)LVdP/dt] and relaxation; [(-)LVdP/dt], along with an increased left ventricular end diastolic pressure (LVEDP). Subsequent to changes in heart rate and arterial pressure, isoproterenol also decreased rate pressure product. Present study findings clearly demonstrate the detrimental outcome of isoproterenol induced-oxidative stress on cardiac function and tissue antioxidant defense and substantiate its suitability as an animal model for the evaluation of cardioprotective agents.

Hepatoprotective and antioxidant actions of an extract of the russian thistle in paracetamol hepatitis in rats

The effects of polyphenol-containing hepatoprotectors of plant origin, i.e., an extract of the Russian thistle and silymarin, on liver metabolism after paracetamol-induced damage were studied in rats. Both hepatoprotectors decreased the signs of paracetamol hepatotoxicity and promoted recovery of the major functions of the liver. Russian thistle extract and to a lesser extent silymarin prevented the formation of lipid peroxidation products, i.e., diene conjugates, Schiff bases, and malondialdehyde, in the liver, produced reductions in blood aminotransferases, y-glutamyltranspeptidase, acid and alkaline phosphatases, and phospholipase A levels, decreased the total bilirubin concentration, and activated the detoxification of bilirubin, phenols, and ammonia.

Formation of Nε-(Carboxymethyl)lysine and Loss of Lysine in Casein Glucose−Fatty Acid Model Systems

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs) form when proteins are heated with reducing sugar or lipid. N(epsilon)-(Carboxymethyl)lysine (CML) is the most commonly studied AGE/ALE in foods, but the relative importance of dietary sugar and lipid as its precursors is uncertain. The aim of this study was to determine the relative amounts of CML formed from fatty acid and glucose in a model food system. Model systems were prepared by heating casein (3.2%) with glucose or fatty acid (oleic, linoleic, linolenic, or arachidonic acid) (200 mM) or a mixture of glucose and linolenic acid (200 mM of each precursor) at 95 degrees C for up to 8 h. CML was determined by ultrapressure liquid chromatography-tandem mass spectrometry. The amount of CML formed from casein and glucose incubated at 95 degrees C for 8 h was 15-fold higher than that obtained when casein was heated with arachidonic acid under the same conditions. However, the loss of lysine in the casein-arachidonic acid incubations was 83% compared to 54% loss in the casein-glucose incubations. The loss of lysine in casein-fatty acid model systems increased with degree of unsaturation of the fatty acid. The formation of lipid peroxidation products during oxidation of fatty acids might be a potent factor for loss of lysine in the casein-fatty acid systems.

Time dependent formation of markers of oxidative stress induced by a high fat diet supplemented or unsupplemented with vitamin E in pigs

The time dependent formation of oxidative damage induced by polyunsaturated fat in the diet was investigated in an experiment with pigs as a model for humans. The role of vitamin E in the prevention of oxidative stress was also studied. Twenty-four growing pigs were penned individually and after an adaptation period divided into three groups. All groups received isocaloric daily rations composed of a basal diet isocalorically supplemented with: starch, linseed oil or linseed oil and vitamin E. Oxidative stress was evaluated by measuring the degree of lymphocyte and granulocyte nuclear DNA damage, concentration of malondialdehyde (MDA) in blood plasma, 24-hour urine MDA excretion rate and concentration of vitamin E isomers in the blood at the beginning, after 24 hours, after 6 days and at the end of the 22 day experimental period. The results confirmed that a high proportion of polyunsaturated fat in the diet increased lymphocyte and granulocyte DNA damage only after 6 days. The lymphocytes appear to be more sensitive to this type of oxidative stress than granulocytes. The MDA concentration in the blood and urinary MDA excretion after 24 hours of oxidative stress seem to be more accurate indicators than the rate of lymphocyte and especially granulocyte DNA damage. Vitamin E supplementation effectively protects the blood cells against increased DNA damage during the whole course of the experiment, but failed to reduce MDA formation significantly 24 hours and 6 days after the beginning of oxidative load. The study further suggests that supplementation of vitamin E is able to completely prevent DNA damage of both types of investigated blood cells at any time, but is only able to reduce the formation of lipid peroxidation products after prolonged treatment.

Inhibition of oxidative stress and apoptosis enables extended maintenance of integrity and function of isolated hepatocytes in suspension

Isolated hepatocytes in suspension may offer an alternative culture system for bioartificial liver devices. However, maintenance of isolated hepatocyte suspensions in conventional media leads to rapid loss of cell integrity. The aim of this study was to develop a modified medium to better maintain hepatocyte integrity. Isolated rat hepatocytes were prepared by collagenase digestion. Hepatocytes were purified in a Percoll gradient, suspended in bicarbonate buffered isotonic saline supplemented with d-alpha-tocopherol succinate and glucose and medium changed at 24 h (modified medium). The properties of cells treated this way were compared with those prepared by collagenase digestion and suspension in bicarbonate buffered isotonic saline (basic medium). Both media were maintained at 30 degrees C for 48 h on an orbital shaker. Markers for oxidative stress, apoptosis and metabolic function were measured enzymatically. Cell morphology was assessed by electron microscopy. When compared to collagenase-isolated hepatocytes maintained in basic medium, hepatocytes purified by Percoll (Amersham Biosciences, Castle Hill, Australia) and maintained in modified medium demonstrated significantly increased glutathione (GSH) and GSH : glutathione disulphide (GSSH) ratios, decreased lipid peroxidation product formation, decreased caspase-3 protease activity, reduced uptake of trypan blue and loss of lactate dehydrogenase (LDH) and increase preservation of cellular adenosine triphosphate concentration ([ATP]), urea synthesis, ammonia removal and glycogen content. Cell morphology was substantially preserved following 48 h of maintenance in the modified medium. The use of Percoll and modified medium reduces cell injury and apoptosis and greatly improves maintenance of cell function and morphology. The modifications reported here and the use of isolated hepatocyte suspensions in bioartificial liver devices are worthy of further investigation.

The preventive effects of heparin–superoxide dismutase on carbon tetrachloride-induced acute liver failure and hepatic fibrosis in mice

In this study, the effects of heparin-superoxide dismutase conjugate (heparin-SOD) on carbon tetrachloride (CCl4)-induced acute liver failure and hepatic fibrosis were evaluated. To investigate the effects of heparin-SOD on acute liver failure, heparin-SOD was administered to CCl4-treated mice by intravenous injection. Biochemical indicators, such as glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT), GSH (glutathione), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were determined 24 h after CCl4 treatment. The development of CCl4-induced acute liver failure altered the redox state with a decreased hepatic GSH and increased formation of lipid peroxidative products, which were partially normalized by treatment with heparin-SOD or heparin + SOD. Compared with other groups, the acute liver injury of heparin-SOD group was significantly lessened (reduced activities of GOT/GPT, MDA, and increased activities of GSH). To investigate the effects of heparin-SOD on hepatic fibrosis, heparin-SOD and CCl4 were co-administered by intraperitoneal injection twice a week for 12 weeks. Histological and hepatic hydroxyproline examination revealed that heparin-SOD could significantly prevent the progression of hepatic fibrosis. Moreover, real-time PCR was used to determine transforming growth factor-beta1 (TGF-beta1), metalloproteinase-2 (MMP-2), fibronectin, and collagen-I expression. Significantly, greater fibrosis and TGF-beta1, MMP-2, fibronectin, and collagen-I expression were found in the liver of CCl4-induced mice at the end of 12th week. Heparin-SOD could markedly attenuate the mRNA expression of TGF-beta1, MMP-2, and collagen-I. Western blots of tissue homogenates revealed that the protein expression of TGF-beta1 was substantially reduce also by heparin-SOD treatment. These results demonstrate that administration of heparin-SOD may be useful in the treatment and prevention of acute liver failure and hepatic fibrosis.

Lipid Peroxidation Products Formation with Various Intravenous Iron Preparations in Chronic Kidney Disease

The role of intravenous iron in contributing to oxidative stress and endothelial dysfunction in chronic kidney disease (CKD) is debatable. The present study assessed differences in fasting plasma malondialdehyde (pMDA) levels 30 minutes before and after intravenous infusion of low molecular weight iron dextran (ID) (n = 19), iron-sucrose (IS) (n = 20), and sodium ferrigluconate complex (SFGC) (n = 20) in stage 3 and 4 CKD patients. Post-infusion pMDA levels were significantly raised with respect to baseline (p < 0.001). pMDA was significantly higher in the SFGC group vs. IS (3.02 ± 0.84 μmol/L vs. 2.82 ± 0.44 μmol/L, p = 0.034) or SFGC vs. ID (3.02 ± 0.84 μmol/L vs. 2.92 ± 0.20 μmol/L, p = 0.048). There was no difference between IS vs. ID (2.82 ± 0.44 μmol/L vs. 2.92 ± 0.20 μmol/L, p = 0.21). To conclude, all forms of parenteral iron, especially SFGC, significantly raise pMDA levels in the immediate post-transfusion period.

Curcumin analogue inhibits lipid peroxidation in a freshwater teleost, Anabas testudineus (Bloch)—an in vitro and in vivo study

The effect of a synthetic curcumin analogue (salicylcurcumin) on fish lipid peroxidation was investigated in both in vitro and in vivo conditions using a teleost model Anabas testudineus (Bloch). Curcumin analogue inhibited the formation of lipid peroxidation products and thiobarbituric acid reactive substances (TBARS) content at the three concentrations (10(-2) M, 10(-3) M and 10(-4) M) in vitro. TBARS content was reduced by 80% in the liver and 68% in brain by the higher concentration of salicylcurcumin. For in vivo study, salicylcurcumin (0.5%) was supplemented along with the basal feed for a period of 60 days. It produced a 60% reduction in liver TBARS content. The antioxidant enzyme superoxide dismutase (SOD) was stimulated, whereas catalase (CAT) and glutathione peroxidase (GPx) were inhibited. Glutathione (GSH) was reduced and glutathione reductase (GR) unchanged. Even though there was an increase in SOD activity, the CAT and GPx did not increase accordingly, maybe due to the direct scavenging of H(2)O(2) by salicylcurcumin. The protein content also increased in the curcumin-fed animals, indicating a positive growth-promoting effect. Therefore, it would be beneficial to supplement salicylcurcumin along with the aquaculture feed in order to help the fish to cope with adverse conditions in the environment. This would increase the survival rate, disease resistance and ultimately the growth rate.

Protective Effect of Extract from Paeonia lactiflora and Astragalus membranaceus against Liver Injury Induced by Bacillus Calmette‐Guérin and Lipopolysaccharide in Mice

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract from the roots of P. lactiflora and A. membranaceus demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. The present study was carried out to investigate the effects of P. lactiflora and A. membranaceus extract on immunological liver injury in mice induced by Bacillus Calmette-Guérin and lipopolysaccharide (BCG/LPS) and to explore a possible mechanism. After administration of P. lactiflora and A. membranaceus (60, 120 and 240 mg/kg, intragastrically) daily for 10 days, the extract significantly reduced the degree of liver damage in BCG/LPS-induced liver injury, as well as the elevation of serum transaminase activities and level of nitric oxide in live injury mice. The extract also restored the decrease in superoxide dismutase and glutathione peroxidase activities and inhibited the formation of lipid peroxidative products. Moreover, P. lactiflora and A. membranaceus (60, 120 and 240 mg/kg, intragastrically) repressed high levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) from peritoneal macrophages. In the primary cultured Kupffer cells, P. lactiflora and A. membranaceus also significantly decreased the production of TNF-alpha and IL-1 in cells stimulated with LPS (5 microg/ml). These results suggest that P. lactiflora and A. membranaceus have a protective effect on BCG/LPS-induced liver injury mice, which might be associated with the antioxidant properties, ability to reduce nitric oxide production and suppression of Kupffer cell activity and pro-inflammatory mediator and cytokines production.

ANTIRADICAL PROPERTY OF CINNAMON REDUCES FRUCTOSE-INDUCED OXIDATIVE STRESS IN RAT LIVER

ABSTRACT The ingestion of fructose as the sole source of carbohydrate in the diet has prooxidant effects in rats. The aim of the present study was to determine whether the administration of the cinnamon bark extract (CBEt) would prevent fructose-induced oxidative stress in rat liver. An aqueous extract of the bark was prepared, the total polyphenolic content of which was found to be 1.32 mM eugenol equivalents (EE). CBEt was administered at two different doses (0.2 mL containing 0.264 µmol EE and 2.0 mL containing 2.64 µmol EE) for 60 days to rats fed with a high-fructose diet (60 g/100 g diet). CBEt at a high dose (2.0 mL) reduced the formation of lipid peroxidation products, namely, thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LHPs) in the plasma and liver, and replenished the enzymatic and nonenzymatic antioxidant system in the blood and liver. The aqueous extract also inhibited TBARS formation induced by the Fe 2+ –ascorbate system in the control rat liver homogenate in vitro and scavenged superoxide and hydroxyl radicals in a dose-dependent manner. Among the various doses studied, the maximum inhibition of lipid peroxidation was observed at 264 µM EE. The positive effects of cinnamon could be attributed to the presence of phenolic phytochemicals in the water-soluble portion of the bark. PRACTICAL APPLICATIONS The insulin-potentiating actions of cinnamon in type 2 diabetes is documented in the literature. We investigated the effect of the administration of cinnamon (Cinnamomum zeylanicum) bark on the oxidant–antioxidant balance in high fructose-induced rat model of insulin resistance. Cinnamon bark (80 mg/day) reduced the formation of lipid peroxidation products and replenished the enzymatic and nonenzymatic antioxidant system in blood and liver. The aqueous extract of the bark remarkably inhibited lipid peroxidation induced by Fe2+–ascorbate system in the control rat liver in vitro and scavenged superoxide and hydroxyl radicals in a dose-dependent manner. The demonstration that cinnamon limits oxidative stress in this animal model of insulin resistance could be significant, considering the increased use of fructose in the food industry and the rising prevalence of type 2 diabetes. Regular inclusion of cinnamon in the daily diet could be beneficial in alleviating diseases that involve oxidative stress.

Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine

A growing body of epidemiological, clinical, and experimental evidence has underscored both the pharmacological potential and the nutritional value of dietary fish oil enriched in very long chain n − 3 PUFAs such as docosahexaenoic acid (DHA, 22:6, n − 3) and eicosapentaenoic acid (EPA, 20:5, n − 3). The broad health benefits of very long chain n − 3 PUFAs and the pleiotropic effects of dietary fish oil and DHA have been proposed to involve alterations in membrane structure and function, eicosanoid metabolism, gene expression and the formation of lipid peroxidation products, although a comprehensive understanding of the mechanisms of action has yet to be elucidated. In this review, we present data demonstrating that DHA selectively modulates the subcellular localization of lipidated signaling proteins depending on their transport pathway, which may be universally applied to other lipidated protein trafficking. An interesting possibility raised by the current observations is that lipidated proteins may exhibit different subcellular distribution profiles in various tissues, which contain a distinct membrane lipid composition. In addition, the current findings clearly indicate that subcellular localization of proteins with a certain trafficking pathway can be subjected to selective regulation by dietary manipulation. This form of regulated plasma membrane targeting of a select subset of upstream signaling proteins may provide cells with the flexibility to coordinate the arrangement of signaling translators on the cell surface. Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment.

High susceptibility of neonatal mice to molecular, biochemical and cytogenetic alterations induced by environmental cigarette smoke and light

Our recent studies have shown that both cigarette smoke and UV-containing light, which are the most widespread and ubiquitous mutagens and carcinogens in the world, cause systemic genotoxic damage in hairless mice. Further studies were designed with the aim of evaluating the induction of genotoxic and carcinogenic effects in Swiss albino mice exposed to smoke and/or light since birth. We observed that a 4-month whole-body exposure of mice to mainstream cigarette smoke, starting at birth, caused an early and potent carcinogenic response in the lung and other organs. Our further experiments showed that exposure of mice to environmental cigarette smoke, during the first 5 weeks of life, resulted in a variety of significant alterations of intermediate biomarkers, including cytogenetic damage in bone marrow and peripheral blood, formation of lipid peroxidation products, increase of bulky DNA adduct levels, induction of oxidative DNA damage, and overexpression of OGG1 gene in lung, stimulation of apoptosis, hyperproliferation and loss of Fhit protein in pulmonary alveolar macrophages and/or bronchial epithelial cells, and early histopathological alterations in the respiratory tract. Moreover, exposure of mice to UV-containing light, mimicking solar irradiation, significantly enhanced oxidative DNA damage and bulky DNA adduct levels in lung, and synergized with smoke in inducing molecular alterations in the respiratory tract. The baseline OGG1 expression in lung was particularly high at birth and decreased in post-weanling mice. Oxidative DNA damage and other investigated end-points exhibited differential patterns in post-weanling mice and adult mice. The findings of these studies provide a mechanistic clue to the general concept that the neonatal period and early stages of life are critical in affecting susceptibility to carcinogens.

Green tea polyphenol epigallocatechin-3-gallate inhibits oxidative damage and preventive effects on carbon tetrachloride–induced hepatic fibrosis

The aim of the study was to examine the effects of epigallocatechin-3-gallate (EGCG) on hepatic fibrogenesis and on cultured hepatic stellate cells (HSCs). The rat model of carbon tetrachloride (CCl 4)-induced hepatic fibrosis was used to assess the effect of daily intraperitoneal injections of EGCG on the indexes of fibrosis. Histological and hepatic hydroxyproline examination revealed that EGCG significantly arrested progression of hepatic fibrosis. EGCG caused significant amelioration of liver injury (reduced activities of serum alanine aminotransferase and aspartate aminotransferase). The development of CCl 4-induced hepatic fibrosis altered the redox state with a decreased hepatic glutathione and increased the formation of lipid peroxidative products, which were partially normalized by treatment with EGCG, respectively. Moreover, EGCG markedly attenuated HSC activation as well as matrix metalloproteinase (MMP)-2 activity. In cultured stellate cell, the expression of MMP-2 mRNA and protein were substantially reduced by EGCG treatment. Concanavalin A-induced activation of secreted MMP-2 was inhibited by EGCG through the influence of membrane type 1-MMP activity. These results demonstrate that administration of EGCG may be useful in the treatment and prevention of hepatic fibrosis.