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Lipid Peroxidation Products (lipid + peroxidation_products)
Selected AbstractsAnthracene photoinduced toxicity to plhc-1 cell line (Poeciliopsis lucida) and the role of lipid peroxidation in toxicityENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2000Jonghoon Choi Abstract Many polycyclic aromatic hydrocarbons (PAHs) are acutely toxic to fish and other aquatic organisms in the presence of solar ultraviolet radiation (SUVR) of environmentally realistic intensities. In the present study, the photoinduced toxicity of a PAH (anthracene; ANT) to topminnow hepatoma cell line (PLHC-1) was assessed. After the toxicity was characterized, the role of lipid peroxidation in PAH photoinduced toxicity was examined by measuring lipid peroxidation products and by assessing the effect of lipid peroxidation antagonist (Trolox) treatment. In cytotoxicity tests using two assays (MTT, neutral red), the SUVR/ANT treatment elicited toxicity to PLHC-1 cells in a concentration- and SUVR (exposure duration and intensity)-dependent pattern. As found in previous organism-level studies, no significant cytotoxicity was observed in the cells exposed either to fluorescent light/ANT or to SUVR only. The SUVR/ANT treatment elicited the lipid peroxidation process and Trolox pretreatment significantly reduced SUVR/ANT-induced cell mortality. Microscopic observation showed that Trolox pretreatment relieved the SUVR/ANT-inflicted damage, such as cell shrinkage and membrane disruption. Together with a recent finding in our lab that increased production of superoxide anion and a lipid peroxidation product (malondialdehyde) was found in SUVR/ANT-treated fish microsomes, the present study suggests that reactive oxygen radical-induced lipid peroxidation is an important factor in PAH photoinduced toxicity to fish. [source] Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct,ligated rats,HEPATOLOGY, Issue 5 2005Ramón Bataller Recent evidence indicates that the renin,angiotensin system (RAS) plays a major role in liver fibrosis. Here, we investigate whether the circulatory RAS, which is frequently activated in patients with chronic liver disease, contributes to fibrosis progression. To test this hypothesis, we increased circulatory angiotensin II (Ang II) levels in rats undergoing biliary fibrosis. Saline or Ang II (25 ng/kg/h) were infused into bile duct,ligated rats for 2 weeks through a subcutaneous pump. Ang II infusion increased serum levels of Ang II and augmented bile duct ligation,induced liver injury, as assessed by elevated liver serum enzymes. Moreover, it increased the hepatic concentration of inflammatory proteins (tumor necrosis factor , and interleukin 1,) and the infiltration of CD43-positive inflammatory cells. Ang II infusion also favored the development of vascular thrombosis and increased the procoagulant activity of tissue factor in the liver. Livers from bile duct,ligated rats infused with Ang II showed increased transforming growth factor ,1 content, collagen deposition, accumulation of smooth muscle ,-actin,positive cells, and lipid peroxidation products. Moreover, Ang II infusion stimulated phosphorylation of c-Jun and p42/44 mitogen-activated protein kinase and increased proliferation of bile duct cells. In cultured rat hepatic stellate cells (HSCs), Ang II (10,8 mol/L) increased intracellular calcium and stimulated reactive oxygen species formation, cellular proliferation and secretion of proinflammatory cytokines. Moreover, Ang II stimulated the procoagulant activity of HSCs, a newly described biological function for these cells. In conclusion, increased systemic Ang II augments hepatic fibrosis and promotes inflammation, oxidative stress, and thrombogenic events. (HEPATOLOGY 2005;41:1046,1055.) [source] The 8-epimer of prostaglandin F2,, a marker of lipid peroxidation and oxidative stress, is decreased in the nipple aspirate fluid of women with breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Ferdinando Mannello Abstract Breast cancer (BC), a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. Whether lipid peroxidation in the mammary gland promotes or prevents tumorigenesis is unclear. Malondialdehyde (MDA) and the 8-epimer of Prostaglandin F2, (8-iso-PGF2,), two lipid peroxidation markers, were studied in milk (n = 10), NAF (n = 140) and plasma (n = 35) samples. MDA was detected in all plasma, in 80% of milk samples and in 95% of NAF samples. MDA levels in NAF and plasma were significantly higher than in milk (p = 0.016 and p = 0.029, respectively). We found no significant difference between levels of MDA in NAF samples from BC patients compared to healthy controls. 8-iso-PGF2, was detectable in all samples. 8-iso-PGF2, median levels in NAF were significantly higher than in both milk and plasma (p < 0.0001). The highest 8-iso-PGF2, levels were found in NAF from healthy women, significantly higher than in women with BC (p < 0.0001). No significant differences were found in both markers after the age-adjustment. High levels of lipid peroxidation products in NAF suggest their in situ production in the nonlactating breast. Active lipid peroxidation may have a physiologic role in the normal mammary gland. Lower levels of 8-iso-PGF2, in NAF from BC patients suggest altered production of arachidonic acid metabolites during breast carcinogenesis. © 2006 Wiley-Liss, Inc. [source] Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental modelsIUBMB LIFE, Issue 11 2008Peter Mřller Abstract The objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid peroxidation products depend on both the duration and severity of the exposure to hypoxia. Largest effects are observed with exposure to hypoxia at high altitude, but other factors, including ultraviolet light, exercise, exertion, and low intake of antioxidants, might contribute to the effect observed in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity. © 2008 IUBMB IUBMB Life, 60(11): 707,723, 2008 [source] (,)Epigallocatechingallate protects the mitochondria against the deleterious effects of lipids, calcium and adenosine triphosphate in isoproterenol induced myocardial infarcted male Wistar ratsJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2008P. T. Devika Abstract The present study was undertaken to evaluate the protective effect of (,)epigallocatechin gallate (EGCG) on mitochondrial lipids, lipid peroxides, Na+/K+ ATPase, calcium and adenosine triphosphate in isoproterenol (ISO) induced myocardial infarction in male Wistar rats. Rats were pretreated with EGCG (30 mg kg,1 body weight) orally using an intragastric tube daily for a period of 21 days. After that, ISO (100 mg kg,1 body weight) was subcutaneously injected to rats at intervals of 24 h for two days. ISO induced rats showed significant increase in the levels of cholesterol, triglycerides and free fatty acids with subsequent decrease in the levels of phospholipids in mitochondrial fraction of the heart. ISO induction also caused significant increase in lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significant decrease in the activity of Na+/K+ ATPase in mitochondrial fraction of the heart. A significant increase in the levels of calcium and significant decrease in the levels of adenosine triphosphate were observed in ISO-induced mitochondrial heart. Prior treatment with EGCG (30 mg kg,1) significantly protected these alterations and maintained normal mitochondrial function. Thus, this study confirmed the protective effect of EGCG on mitochondria in experimentally induced cardiotoxicity in Wistar rats. Copyright © 2008 John Wiley & Sons, Ltd. [source] Dietary vitamin E reduces labile iron in rat tissuesJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2005Wissam Ibrahim Abstract Previous studies have shown that dietary vitamin E reduced generation and/or levels of superoxide. As superoxide has potential to release iron from its transport and storage proteins, and labile or available form of iron is capable of catalyzing the formation of reactive hydroxyl radicals, the effect of dietary vitamin E on labile iron pool was studied in rats. One-month-old Sprague-Dawley male and female rats were fed a basal vitamin E-deficient diet supplemented with 0, 20, 200, or 2,000 IU vitamin E/kg diet for 90 days. The levels of labile iron were measured in the liver, kidney, spleen, heart and skeletal muscle. Additionally, the levels of lipid peroxidation products were measured. The results showed that, except for labile iron in the heart of male rats, dietary vitamin E dose dependently reduced the levels of labile iron and lipid peroxidation products in all tissues of male and female rats. The findings suggest that dietary vitamin E may protect against oxidative tissue damage by reducing the generation and/or level of superoxide, which in turn attenuates the release of iron from its protein complexes. © 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:298,303, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20094 [source] Endotoxin increases hepatic susceptibility to lipid peroxidation: A possible role of ironJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2004W. Ibrahim Abstract The purpose of this study was to investigate the possible mechanism by which endotoxin enhances peroxidative damage to membrane lipids. Male B6C3 mice were treated with endotoxin intraperitoneally 0 or 20 mg/kg body weight for 24 h. Freshly prepared liver homogenate was incubated with either 1,5 mM of reduced glutathione (GSH), glucose, H2O2, ascorbic acid (AA), FeSO4, FeCl3, EDTA, FeCl3 plus AA, AA plus EDTA or EDTA plus FeCl3 in phosphate-buffered saline (PBS), pH 7.0, or PBS, at 37°C for 60 min. The levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), were significantly higher in the liver of endotoxin-treated mice, and the values were markedly increased following incubation. Compared to PBS, incubation with H2O2, FeCl3, FeSO4, and AA, but not glucose, significantly enhanced TBAR formation. The greatest increase of TBAR was found when AA and FeCl3 were added together. On the other hand, EDTA and GSH inhibited the formation of TBAR during incubation. When added before AA, EDTA completely inhibited the peroxidative effect of AA or FeSO4, and when added subsequent to AA, EDTA partially prevented the adverse effect of AA. The results obtained suggest that ionic iron plays an important role in initiating endotoxin-induced peroxidative damage to membrane lipids, and that AA may be involved in releasing iron from its protein complex and/or maintaining ionic iron in a reduced or catalytic state. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:23,29, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20002 [source] Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid glandJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005Malgorzata Karbownik Abstract Potassium bromate (KBrO3) is a prooxidant and carcinogen, inducing thyroid tumors. Melatonin and indole-3-propionic acid (IPA) are effective antioxidants. Some antioxidative effects of propylothiouracil (PTU),a thyrostatic drug,have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the thyroids, collected from rats treated with KBrO3, and in homogenates of porcine thyroids, incubated in the presence of KBrO3. Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). Homogenates of porcine thyroids were incubated for 30 min in the presence of KBrO3 (5 mM) plus one of the antioxidants: melatonin (0.01, 0.1, 0.5, 1.0, 5.0, 7.5 mM), or IPA (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM), or PTU (0.01, 0.1, 0.5, 1.0, 5.0, 7.5, 10.0 mM). The level of lipid peroxidation products (MDA,+,4-HDA) was measured spectrophotometrically in thyroid homogenates. In vivo pretreatment with either melatonin or with IPA or with PTU decreased lipid peroxidation caused by KBrO3,injections in rat thyroid gland. Under in vitro conditions, PTU (5.0, 7.5, and 10.0 mM), but neither melatonin nor IPA, reduced KBrO3 -related lipid peroxidation in the homogenates of porcine thyroids. In conclusion, melatonin and IPA may be of great value as protective agents under conditions of exposure to KBrO3. © 2005 Wiley-Liss, Inc. [source] Influence of therapy on the antioxidant status in patients with melanomaJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2008V. Gadjeva DSc Summary Background and objective:, Some anticancer drugs can result in increased production of reactive oxygen species (ROS). Alkylating agents are the most frequently used drugs in chemotherapeutic regimens for the treatment of malignant melanoma. It is known that triazenes exhibit in vivo activity by alkylation of nucleic acids and proteins, but there is no data about ROS formation during oxidative metabolism. Single agents of most interest for treatment of malignant melanomas include 5-(3,3-dimethyltriazene-1-yl)-imidazole-4-carboxamide (DTIC) and nitrosoureas such as 1-(2-chloroethyl) -3-cyclohexyl-1-nitrosourea (CCNU), but complete response to these drugs is rare. The present study aimed to determine whether an oxidative stress occurs during the clinical course of melanoma and the influence of therapy on the antioxidant status of patients with melanoma. For this purpose, we investigated plasma concentrations of MDA as indices of the levels of lipid peroxidation products. In addition, we studied the activities of the antioxidant enzymes superoxide dismutases (SOD) and catalase (CAT) in patients with melanoma before any treatment, after surgical removal of melanoma, and after chemotherapy with DTIC or in combination with CCNU of the operated patients. Methods:, Twenty one patients with melanoma were studied. Patients were operated prior to chemotherapy. After recovery for 10,20 days postoperatively, they were studied again for MDA, SOD and CAT activity. The patients were divided into two groups according to the chemotherapy (3,7 treatment cycles): with DTIC , given orally daily for 5 days, every 3 weeks as a single 2200 mg/kg dose and with the combination , DTIC (the same dose) + CCNU , administered orally at a dosage of 120 mg/m2 once every 40 days in accordance with protocols, approved by the Bulgarian Ministry of Health. The total amount of lipid peroxidation products in plasma was assayed. Results and discussion:, Plasma levels of MDA and CAT activity were significantly higher, and erythrocyte SOD activity significantly lower, in patients with melanoma, than in control healthy volunteers (P < 0·0001). Ten to twenty days after surgery, oxidative stress decreased but levels of MDA increased as a result of therapy. Important sources of increased ROS production may be the monocytes, phagocytosis of tumour cells and the cancer tissues. Plasma MDA in patients treated with DTIC + CCNU were significantly higher (P < 0·001), but erythrocyte SOD statistically lower (P < 0·00001), compared with patients treated with DTIC only. However, a combination of DTIC + CCNU did not attenuate oxidative stress, or reduced antioxidant status. Patients treated with this combination are at bigger risk of oxidative injury. Therefore, this disturbance might be due to augmented generation of toxic ROS, possibly from the metabolism of CCNU. Conclusion:, Increased oxidative stress follows an imbalance in antioxidant defence in non-treated patients with melanoma. The impaired antioxidant system favours accumulation of ROS, which may promote the cancer process. After complete removal of melanoma tissues, oxidative stress decreased. The antioxidant status of melanoma patients operated on was influenced by the different chemotherapeutic regimens used and may play an important role in the response. Patients on DTIC + CCNU are at higher risk of oxidative injury. This drug combination probably exerts its toxic activity by ROS, which could be products of the metabolism of CCNU. [source] Curcuma Aromatica Inhibits Diabetic Nephropathy in the RatJOURNAL OF FOOD SCIENCE, Issue 9 2006Ji-Young Hong ABSTRACT:, To test the possible involvement of reactive oxygen species (ROS) in the etiology of diabetic complications and therapeutic potential of antioxidant biofactors, we studied the effects of Curcuma aromatica (C. aromatica) on the pathologic events in streptozotocin-treated diabetic rats. Administration of streptozotocin (100 mg/kg, i.p.) increased plasma levels of glucose, triglyceride, cholesterol, urea nitrogen (BUN), creatinine, and lipid peroxidation products but decreased plasma albumin levels and suppressed the growth of animals. Histological examination revealed a marked injury in renal glomeruli and proximal tubules with concomitant occurrence of 8-hydroxy-2,-deoxyguanosine (8-OHdG) and mitochondrial 4-hydroxy-2-nonenal (4-HNE). Urinary excretion of 8-OHdG was also increased in streptozotocin-treated animals. Administration of streptozotocin decreased the mitochondrial localization of both Cu/Zn-superoxide dismutase (SOD) and cytochrome C in the kidney without affecting the localization of Mn-SOD. When animals were given 1.5%C. aromatica- containing diet for 1 wk before and 8 wk after administration of streptozotocin, all the events induced by streptozotocin except for hyperglycemia decreased markedly. Thus, C. aromatica may have therapeutic potential for the prevention of hyperglycemia-associated diabetic complications. [source] Tryptophan metabolism and oxidative stress in patients with Huntington's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 3 2005N. Stoy Abstract Abnormalities in the kynurenine pathway may play a role in Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes in blood kynurenine pathway metabolites, as well as markers of inflammation and oxidative stress in HD patients and healthy controls. Results showed that the kynurenine : tryptophan ratio was greater in HD than controls in the baseline state and after tryptophan depletion, indicating increased indoleamine dioxygenase activity in HD. Evidence for persistent inflammation in HD was provided by elevated baseline levels of C-reactive protein, neopterin and lipid peroxidation products compared with controls. The kynurenate : kynurenine ratio suggested lower kynurenine aminotransferase activity in patients and the higher levels of kynurenine in patients at baseline, after depletion and loading, do not result in any differences in kynurenic acid levels, providing no supportive evidence for a compensatory neuroprotective role for kynurenic acid. Quinolinic acid showed wide variations in blood levels. The lipid peroxidation data indicate a high level of oxidative stress in HD patients many years after disease onset. Levels of the free radical generators 3-hydroxykynurenine and 3-hydroxyanthranilic acid were decreased in HD patients, and hence did not appear to contribute to the oxidative stress. It is concluded that patients with HD exhibit abnormal handling of tryptophan metabolism and increased oxidative stress, and that these factors could contribute to ongoing brain dysfunction. [source] Protective effect of melatonin against oxidative stress induced by ligature of extra-hepatic biliary duct in rats: comparison with the effect of S-adenosyl- l -methionineJOURNAL OF PINEAL RESEARCH, Issue 3 2000Pedro Montilla López In the present research, we studied the effect of the administration of melatonin or S-adenosyl- l -methionine (S-AMe) on oxidative stress and hepatic cholestasis produced by double ligature of the extra-hepatic biliary duct (LBD) in adult male Wistar rats. Hepatic oxidative stress was evaluated by the changes in the amount of lipid peroxides and by the reduced glutathione content (GSH) in lysates of erythrocytes and homogenates of hepatic tissue. The severity of the cholestasis and hepatic injury were determined by the changes in the plasma enzyme activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), g-glutamyl-transpeptidase (GGT), and levels of albumin, total bilirubin (TB) and direct bilirubin (DB). Either melatonin or S-AMe were administered daily 3 days before LBD, and for 10 days after biliary obstruction. LDB caused highly significant increases in plasma enzyme activities and in bilirubin and lipid peroxides levels in erythrocytes and hepatic tissue. At the same time, this procedure produced a notable decrease in the GSH pools in these biological media. Both melatonin and S-AMe administration were effective as antioxidants and hepatoprotective substances, although the protective effects of melatonin were superior; it prevented the GSH decrease and reduced significantly the increases in enzyme activities and lipid peroxidation products produced by biliary ligature. S-AMe did not modify the increased GGT activity nor did it decrease greatly the TB levels (43% melatonin vs. 14% S-AMe). However, S-AMe was effective in preventing the loss of GSH in erythrocytes and hepatic tissue, as was melatonin. The obtained data permit the following conclusions. First, the LDB models cause marked hepatic oxidative stress. Second, the participation of free radicals of oxygen in the pathogenecity and severity of cholestasis produced by the acute obstruction of the extra-hepatic biliary duct is likely. Third, the results confirm the function of S-AMe as an antioxidant and hepatoprotector. Finally, melatonin is far more potent and provides superior protection as compared to S-AMe. Considering the decrease in oxidative stress and the intensity of cholestasis, these findings have interesting clinical implications for melatonin as a possible therapeutic agent in biliary cholestasis and parenchymatous liver injury. [source] Oxidative effects in uninfected tissue in leaves of French bean (Phaseolus vulgaris) containing soft rots caused by Botrytis cinereaJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 6 2003Ingo Muckenschnabel Abstract Several markers of oxidative processes have been measured in leaves of Phaseolus vulgaris infected with Botrytis cinerea, with the specific objective of investigating changes induced by this necrotrophic pathogen in tissue remote from the lesion. There was a progressive decrease with time in the contents of ascorbic acid (AA) in apparently healthy tissues from infected plants and non-inoculated plants grown under identical high-humidity conditions (abiotically stressed controls), and for periods >48 h this decrease was greater in the infected plants. This decline in AA content was accompanied by an elevation in the intensity of the electron paramagnetic resonance (EPR) signal from adducts of the spin trap ,-(4-pyridyl-1-oxide)- N - t -butylnitrone (POBN), a destabilisation of the (monodehydro) ascorbate radical (Asc·) signal in the presence of POBN, and an increase in the ratio of Asc· to AA in samples studied in the absence of the spin trap. These results are consistent with a shift in redox status to more oxidising conditions in apparently healthy tissue of infected plants and indicate the prevalence of chemical processes that are distinctly different from those in uninfected plants. However, no differences in lipid peroxidation products or the single-peak free radical and Fe(III) (g = 4.27) EPR signals were observed between these tissues distant from the lesions and those from abiotically stressed controls. In addition, the pathogen-derived sesquiterpene toxin botrydial and a second Mn(II) EPR signal, both of which are associated with Botrytis infection, were not detected in these ,apparently healthy' tissues. Copyright © 2003 Society of Chemical Industry [source] Up-regulation of autophagy in small intestine Paneth cells in response to total-body ,-irradiation,,THE JOURNAL OF PATHOLOGY, Issue 2 2009Nikolai V. Gorbunov Abstract Macroautophagy (mAG) is a lysosomal mechanism of degradation of cell self-constituents damaged due to variety of stress factors, including ionizing irradiation. Activation of mAG requires expression of mAG protein Atg8 (LC3) and conversion of its form I (LC3-I) to form II (LC3-II), mediated by redox-sensitive Atg4 protease. We have demonstrated upregulation of this pathway in the innate host defense Paneth cells of the small intestine (SI) due to ionizing irradiation and correlation of this effect with induction of pro-oxidant inducible nitric oxide synthase (iNOS). CD2F1 mice were exposed to 9.25 Gy ,-ionizing irradiation. Small intestinal specimens were collected during 7 days after ionizing irradiation. Assessment of ionizing irradiation-associated alterations in small intestinal crypt and villus cells and activation of the mAG pathway was conducted using microscopical and biochemical techniques. Analysis of iNOS protein and the associated formation of nitrites and lipid peroxidation products was performed using immunoblotting and biochemical analysis, and revealed increases in iNOS protein, nitrate levels and oxidative stress at day 1 following ionizing irradiation. Increase in immunoreactivity of LC3 protein in the crypt cells was observed at day 7 following ionizing irradiation. This effect predominantly occurred in the CD15-positive Paneth cells and was associated with accumulation of LC3-II isoform. The formation of autophagosomes in Paneth cells was confirmed by transmission electron microscopy (TEM). Up-regulation of LC3 pathway in the irradiated SI was accompanied by a decreased protein,protein interaction between LC3 and chaperone heat shock protein 70. A high-level of LC3-immunoreactivity in vacuole-shaped structures was spatially co-localized with immunoreactivity of 3-nitro-tyrosine. The observed effects were diminished in iNOS knockout B6.129P2- NOS2tm1Lau/J mice subjected to the same treatments. We postulate that the observed up-regulation of mAG in the irradiated small intestine is at least in part mediated by the iNOS signalling mechanism. Published in 2009 by John Wiley & Sons, Ltd. [source] Production of lipid peroxidation products in osteoarthritic tissues: New evidence linking 4-hydroxynonenal to cartilage degradation,ARTHRITIS & RHEUMATISM, Issue 1 2006Barbara Morquette MSc Objective The lipid peroxidation product 4-hydroxynonenal (HNE) is prominently produced in osteoarthritic (OA) synovial cells, but its specific contribution to cartilage destruction is not understood. This study was designed to test whether HNE signaling and binding are involved in OA cartilage degradation through type II collagen (CII) and matrix metalloproteinase 13 (MMP-13) modulation. Methods HNE levels in synovial fluid and in isolated OA chondrocytes treated with free radical donors were determined by enzyme-linked immunosorbent assay. The formation of the HNE/CII adducts was measured in cartilage explants by immunoprecipitation. Levels of CII and MMP-13 messenger RNA and protein were determined by reverse transcription,polymerase chain reaction, Western blotting, and by the use of commercial kits. Results Levels of HNE/protein adducts were higher in OA synovial fluid compared with normal synovial fluid and were higher in OA chondrocytes treated with free radical donors compared with untreated cells. In cartilage explants, HNE induced CII cleavage, as established by the generation of neoepitopes. The level of HNE/CII adducts was increased in OA cartilage explants incubated with free radical donors. Modification of CII by HNE accelerated its degradation by active MMP-13. In isolated OA chondrocytes, HNE inhibited the expression of CII and tissue inhibitor of metalloproteinases 1 and induced MMP-13 mainly through activation of p38 MAPK. In vitro, HNE binding to MMP-13 activated this enzyme at a molar ratio of 1:100 (MMP-13 to HNE). Conclusion The increased level of HNE in OA cartilage and the ability of HNE to induce transcriptional and posttranslational modifications of CII and MMP-13 suggest that this aldehyde could play a role in OA. [source] Studies of phospholipid oxidation by electrospray mass spectrometry: From analysis in cells to biological effectsBIOFACTORS, Issue 1-4 2005Corinne M. Spickett Abstract The oxidation of lipids is important in many pathological conditions and lipid peroxidation products such as 4-hydroxynonenal (HNE) and other aldehydes are commonly measured as biomarkers of oxidative stress. However, it is often useful to complement this with analysis of the original oxidized phospholipid. Electrospray mass spectrometry (ESMS) provides an informative method for detecting oxidative alterations to phospholipids, and has been used to investigate oxidative damage to cells, and low-density lipoprotein, as well as for the analysis of oxidized phosphatidylcholines present in atherosclerotic plaque material. There is increasing evidence that intact oxidized phospholipids have biological effects; in particular, oxidation products of 1-palmitoyl-2-arachidonoyl- sn -glycerophosphocholine (PAPC) have been found to cause inflammatory responses, which could be potentially important in the progression of atherosclerosis. The effects of chlorohydrin derivatives of lipids have been much less studied, but it is clear that free fatty acid chlorohydrins and phosphatidylcholine chlorohydrins are toxic to cells at concentrations above 10 micromolar, a range comparable to that of HNE and oxidized PAPC. There is some evidence that chlorohydrins have biological effects that may be relevant to atherosclerosis, but further work is needed to elucidate their pro-inflammatory properties, and to understand the mechanisms and balance of biological effects that could result from oxidation of complex mixtures of lipids in a pathophysiological situation. [source] In this issue: Biotechnology Journal 9/2010BIOTECHNOLOGY JOURNAL, Issue 9 2010Article first published online: 10 SEP 2010 Linking obesity and colorectal cancer Sung and Bae, Biotechnol. J. 2010, 5, 930,941 Obesity is known as one of the most closely related risk factors of colorectal cancer (CRC). However, due to the complicated nature of the diet, it has been very difficult to provide clear explanations and molecular mechanisms for the role of dietary components in carcinogenesis. Nutrigenomics has become a powerful tool to study the relationships between food components and genes. It includes nutrigenetics (dealing with genetic variations related to phenotypic changes in response to diet), nutritional epigenomics and nutritional transcriptomics/proteomics/metabolomics. This review summarizes data on genes, proteins and metabolites that are related to either obesity or CRC and candidate molecules that may link obesity and CRC. The application of bioinformatics helps to perform large-scale network analysis to study cause-effect relationships between dietary components and CRC in the future. Hepatoprotective effects of oleuropein Kim et al., Biotechnol. J. 2010, 5, 950,960 Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species and has a protective effect against non-alcoholic fatty liver disease (NAFLD) in vivo. To gain insights into the molecular mechanisms of its hepatoprotective action the group of Taesun Park (Seoul, Korea) fed mice with a high fat diet supplemented with oleuropein. Then, liver tissue was subjected to DNA microarray analysis. Oleuropein in high fat diet reduced the mRNA level of regulators of hepatic fatty acid uptake and transport. The expression of a number of genes involved in oxidative stress responses, detoxification of lipid peroxidation products and proinflammatory cytokine genes were reduced, while highly regulated transcription factors were implicated in the lipogenesis, inflammation, insulin resistance and fibrosis, underlying the multifactorial effect of oleuropein on NAFLD. Genetic variations in obesity and diabetes Varma et al., Biotechnol. J. 2010, 5, 942,949 Obesity is a state of metabolic deregulation and a leading cause for development of type 2 diabetes, which are complex polygenic diseases. Here, authors from the National Centre of Toxicological Research at the FDA (Jefferson, Arizona, USA) used a data mining approach to evaluate the role of carbohydrate metabolic pathway genes in the development of obesity and type 2 diabetes. Data from public databases were used to map the position of these genes to known quantitative trait loci (QTL) and to find sequence and structural genetic variants such as single nucleotide polymorphisms (SNPs). The results demonstrated that a majority of carbohydrate metabolic pathways genes are associated with QTL for obesity and many for type 2 diabetes. This data mining approach can establish a strategy for interpreting an individual's risk factor for disease development, instead of population attributable risks. [source] Hepatoprotective effect of oleuropein in mice: Mechanisms uncovered by gene expression profilingBIOTECHNOLOGY JOURNAL, Issue 9 2010Yunjung Kim Abstract Oleuropein, an active constituent of olive leaf, has a variety of pharmacological activities associated with its capacity to scavenge reactive oxygen species. Oleuropein is also reported to have protective effects against non-alcoholic fatty liver disease (NAFLD) in vivo. In this study, gene expression profiling of hepatic tissues was examined, and transcription factors (TFs) with target genes that were modulated by oleuropein were identified to gain insights into the molecular mechanisms for the hepatoprotective action of this compound. C57BL/6N mice were fed either a high-fat diet (HFD) or 0.03% oleuropein-supplemented HFD for 10 weeks, after which their livers were subjected to oligo DNA microarray analysis. The oleuropein with which the HFD was supplemented reduced the hepatic mRNA level of the genes that encoded the key regulators of the hepatic fatty acid uptake and transport. In addition, the oleuropein reduced the expression of a number of hepatic genes involved in the oxidative stress responses and detoxification of lipid peroxidation products and proinflammatory cytokine genes. The (putative) candidate TFs that bound to the promoters of the genes regulated at least threefold (both up and down) by oleuropein were implicated in the lipogenesis, inflammation, insulin resistance, fibrosis, and cell proliferation and differentiation, which implies that the mechanisms that underlie the beneficial effects of oleuropein on NAFLD may be multifactorial. [source] Lipid peroxidation and total antioxidant status in patients with breast cancerCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2007Derya Erten, ener Abstract Oxidative stress is considered to be involved in the pathophysiology of all cancers. The aim of this study is to examine oxidative stress and antioxidant status in patients with breast cancer by evaluation of the serum levels of total antioxidant capacity (TAC) and lipid peroxidation products as malondialdehyde (MDA) and lipid hydroperoxide and to investigate the relationship between these parameters, oxidative stress and serum lipids and lipoproteins. In our study, serum TAC, MDA, lipid hydroperoxide, HDL-cholesterol, VLDL-cholesterol, LDL-cholesterol, total cholesterol, triacylglycerol (TAG), albumin and uric acid levels of 56-breast cancer patients in different clinical stages and 18 healthy women were determined. Significantly lower-levels of TAC were detected in patients with breast cancer in comparison to controls (2.01,±,0.01,mmol/l and 2.07,±,0.03,mmol/l, respectively, p,<,0.05). Serum MDA levels of the patients were higher compared to the controls (3.64,±,0.25,µM and 2.72,±,0.22,µM, respectively, p,<,0.05). No significant difference between lipid hydroperoxide levels of patients and controls was found (0.33,±,0.05,µM and 0.32,±,0.01,µM, respectively, p,>,0.05). These data show that lower TAC and higher MDA levels i.e. increased oxidative stress may be related to breast cancer. Copyright © 2006 John Wiley & Sons, Ltd. [source] Protective effects of melatonin and indole-3-propionic acid against lipid peroxidation, caused by potassium bromate in the rat kidneyCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2006gorzata Karbownik Abstract Potassium bromate (KBrO3) is classified as a carcinogenic agent. KBrO3 induces tumors and prooxidative effects in kidneys. Melatonin is a well known antioxidant and free radical scavenger. Indole-3-propionic acid (IPA), an indole substance, also reveals antioxidative properties. Recently, some antioxidative effects of propylthiouracil (PTU),an antithyroid drug,have been found. The aim of the study was to compare protective effects of melatonin, IPA, and PTU against lipid peroxidation in the kidneys and blood serum and, additionally, in the livers and the lungs, collected from rats, pretreated with KBrO3. Male Wistar rats were administered KBrO3 (110 mg/kg b.w., i.p., on the 10th day of the experiment) and/or melatonin, or IPA (0.0645 mmol/kg b.w., i.p., twice daily, for 10 days), or PTU (0.025% solution in drinking water, for 10 days). The level of lipid peroxidation products,malondialdehyde,+,4-hydroxyalkenals (MDA,+,4-HDA),was measured spectrophotometrically in thyroid homogenates. KBrO3, when injected to rats, significantly increased lipid peroxidation in the kidney homogenates and blood serum, but not in the liver and the lung homogenates. Co-treatment with either melatonin or with IPA, but not with PTU, decreased KBrO3 -induced oxidative damage to lipids in the rat kidneys and serum. In conclusion, melatonin and IPA, which prevent KBrO3 -induced lipid peroxidation in rat kidneys, may be of great value as protective agents under conditions of exposure to KBrO3. Copyright © 2006 John Wiley & Sons, Ltd. [source] Efficacy of piperine, an alkaloidal constituent from Piper nigrum on erythrocyte antioxidant status in high fat diet and antithyroid drug induced hyperlipidemic ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 6 2006Ramasamy Subramaniam Vijayakumar Abstract The main aim of this study was to investigate the effect of piperine on erythrocyte antioxidant status in high fat diet (HFD) and antithyroid drug induced hyperlipidemic rats. Male Wistar rats were divided into eight groups. The first four groups were fed a control diet and in addition were given respectively 1% carboxymethyl cellulose (CMC); 10,mg/kg body weight carbimazole (CM); 10,mg CM,+,40,mg/kg body weight piperine and 10,mg CM,+,2,mg/kg body weight atorvastatin (ATV). A similar pattern was followed for the next four groups except that they were all fed HFD instead of the control diet. Erythrocyte osmotic fragility, total cholesterol, phospholipids, lipid peroxidation products, enzymic and non-enzymic antioxidant status were studied in all experimental groups. Significantly increased osmotic fragility, total cholesterol/phospholipid ratio, thiobarbituric acid reactive substances and lipid hydroperoxides were observed in the plasma and erythrocytes of HFD fed and CM treated rats compared to the control. Superoxide dismutase, catalase, glutathione peroxidase, vitamin E and reduced glutathione in erythrocytes and vitamin C in the plasma were also significantly lowered in HFD fed, antithyroid drug treated rats compared to control animals. Concurrent piperine supplementation along with HFD and antithyroid drug administration normalized erythrocyte osmotic fragility, reduced lipid peroxidation, and improved the enzymic and non-enzymic antioxidant status compared to those rats that did not receive piperine. Thus, our results indicate that piperine supplementation markedly protects erythrocytes from oxidative stress by improving the antioxidant status in HFD fed antithyroid drug treated rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] Isoprenoid pathway dysfunction in chronic fatigue syndromeACTA NEUROPSYCHIATRICA, Issue 5 2003Ravi Kumar Kurup Background and aims:, The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome (CFS). The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has any correlation with these disease states. Methods:, The isoprenoid metabolites , digoxin, dolichol and ubiquinone , RBC membrane Na+ -K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free radical metabolism, glycoconjugate metabolism and RBC membrane composition were also assessed. Results:, Membrane Na+ -K+ ATPase activity and serum magnesium levels were decreased while HMG-CoA reductase activity and serum digoxin levels were increased in CFS. There were increased levels of tryptophan catabolites , nicotine, strychnine, quinolinic acid and serotonin , and decreased levels of tyrosine catabolites ,dopamine, norepinephrine and morphine , in CFS. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycans (GAG) fractions and lysosomal enzymes in CFS. Reduced levels of ubiquinone, reduced glutathione and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in CFS. The biochemical patterns in CFS correlated with those obtained in right hemispheric dominance. Conclusions:, The role of hypothalamic digoxin and neurotransmitter-induced immune activation, altered glycoconjugate metabolism and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive and mitochondrial dysfunction in the pathogenesis of CFS is stressed. CFS occurs in individuals with right hemispheric dominance. [source] KYNURENINE PATHWAY METABOLISM IN PATIENTS WITH OSTEOPOROSIS AFTER 2 YEARS OF DRUG TREATMENTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2006Caroline M Forrest ABSTRACT 1Metabolism of tryptophan along the oxidative pathway via kynurenine results in the production of quinolinic acid and kynurenic acid, which can act on glutamate receptors in peripheral tissues. We have now measured the concentrations of kynurenine pathway metabolites in the plasma of patients with osteoporosis before treatment with drugs, throughout and after 2 years of treatment with the drugs raloxifene or etidronate. Oxidative stress was assessed by measuring levels of the lipid peroxidation products malondialdehyde and 4-hydroxynonenal. Kynurenines were analysed by HPLC. Bone density was measured using dual-energy X-ray absorptiometry scans. 2Patients with osteoporosis showed significantly lower baseline levels of 3-hydroxyanthranilic acid compared with healthy controls, but significantly higher levels of anthranilic acid and lipid peroxidation products. After 2 years treatment with etidronate and calcium, we observed significant therapeutic responses quantified by bone densitometric scanning. Significant improvements were not seen in patients treated with raloxifene. 3In parallel, the levels of 3-hydroxyanthranilic acid, anthranilic acid and lipid peroxidation products were restored to control values by both drug treatments studied and tryptophan levels were increased significantly compared with baseline values. 4The results suggest that tryptophan metabolism is altered in osteoporosis in a manner that could contribute to the oxidative stress and, thus, to progress of the disease. The oxidative metabolism of tryptophan (the kynurenine pathway) could represent a novel target for the development of new drugs for the treatment of osteoporosis. In addition, we noted that etidronate is a more effective drug than raloxifene, but that the simultaneous use of non-steroidal anti-inflammatory drugs may reduce the efficacy of etidronate. [source] | ||||||||||||||||