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Oxidative Stress Markers (oxidative + stress_marker)
Selected AbstractsOxidative stress due to anesthesia and surgical trauma: Importance of early enteral nutritionMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 6 2009Katerina Kotzampassi Abstract Anesthesia and surgical trauma are considered major oxidative and nitrosative stress effectors resulting in the development of SIRS. In this study we evaluated the usefulness of early enteral nutrition after surgical trauma. Sixty male Wistar rats were subjected to midline laparotomy and feeding-gastrostomy. Twenty of these rats served as controls after recovering from the operation stress. The remaining rats received, through gastrostomy, enteral nutrition or placebo-feeding for 24 h. Oxidative stress markers and CC chemokine production were evaluated in rat serum and liver tissue. The operation itself was found to increase nitric oxide (NO) and malondialdehyde (MDA) and to decrease superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as liver tissue energy charge (EC) in relation to controls. The rats receiving enteral feeding exhibited statistically significantly lower levels of NO and MDA, and higher levels of SOD, GSH-Px, and liver EC, in relation to placebo feeding rats. The operation significantly increased the chemokines monocyte chemoattractant protein (MCP)-1 and regulated upon activation, normal T-cell expressed, and secreted (RANTES) in rat serum, while enteral nutrition caused a further significant increase in chemokine levels in serum. mRNA chemokine expression in liver was increased in a similar pattern. These findings indicate that early enteral feeding might play an important role after surgery ameliorating oxidative stress, affecting positively the hepatic EC and regulating, via chemokine production, cell trafficking, and healing process. [source] High Oxidative Stress Is Correlated with Frailty in Elderly ChineseJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2009I-Chien Wu MD OBJECTIVES: To evaluate the relationship between oxidative stress and frailty in elderly people. DESIGN: Cross-sectional study. SETTING: Community and hospital-based outpatient clinic. PARTICIPANTS: Ninety participants aged 65 and older. MEASUREMENTS: Frailty status was determined according to the presence of weak handgrip strength, weight loss, slow walking speed, exhaustion, and low activity level and was classified as frail (,3 criteria), prefrail (1 or 2 criteria), or robust (0 criteria). An oxidative stress marker (serum 8-hydroxy-2,-deoxyguanosine, 8-OHdG), metabolic markers (body mass index, waist,hip ratio, serum lipids, glucose, and albumin), an inflammatory marker (serum high-sensitivity C-reactive protein, hs-CRP), demographic information, and comorbidities (diabetes mellitus, hypertension, congestive heart failure, osteoarthritis, overweight or obesity, impaired fasting plasma glucose, renal insufficiency, and depression) were assessed. RESULTS: Of the 90 participants, 21 (23.3%) were frail, 56 (62.2%) were prefrail, and 13 (14.4%) were robust. Frail subjects had higher median (range) serum 8-OHdG (2.5 ng/mL (1.5,6.2 ng/mL) vs 2.3 ng/mL (0.5,8.1 ng/mL) and 1.0 ng/mL (0.5,5.3 ng/mL)) and serum hs-CRP (2.5 mg/L (0.3,32.1 mg/L) vs 1.8 mg/L (0.3,50.5 mg/L) and 1.7 mg/L (0.3,4.0 mg/L)) levels, lower mean±standard deviation serum albumin levels (4.1±0.4 g/dL vs 4.4±0.4 g/dL and 4.6±0.2 g/dL) and higher mean waist,hip ratios (0.96±0.11 vs 0.91±0.07 and 0.89±0.05)) than prefrail and robust subjects, respectively (P<.05 for all). In multivariable regression analysis, high serum 8-OHdG level was still significantly associated with frailty after adjusting for age, smoking status, comorbidities, waist,hip ratio, serum albumin level, and hs-CRP level. CONCLUSION: High oxidative stress, characterized by high serum 8-OHdG level, was independently associated with frailty in the selected sample of elderly Chinese. [source] Poster Sessions AP13: Novel Techniques and TechnologiesJOURNAL OF NEUROCHEMISTRY, Issue 2002J. K. Yao Studies of the antioxidant defense system and the monoamine metabolic pathways are often complicated by cumbersome analytical methods, which require separate and multistep extraction and chemical reaction procedures. Thus, measurements of multiple parameters are limited in relatively small biological samples. High performance liquid chromatography (HPLC) coupled with a Coulometric Multi-Electrode Array System (CMEAS) provides us a convenient and most sensitive tool to measure low molecular weight, redox-active compounds in biological sample. The deproteinized sample was analyzed on a HPLC coupled with a 16-channel CMEAS, which incremented from 60 to 960 mV in 60 mV steps. Each sample was run on a single column (Meta-250, 4.6 × 250 mm) under a 150-minute complex gradient that ranged from 0% B (A: 1.1% pentane sulfonic acid) to 20% B (B: 0.1 m lithium acetate in mixture of methanol, acetonenitrile and isopropanol), with a flow rate of 0.5 mL/min. We have developed an automated procedure to simultaneously measure various antioxidant, oxidative stress marker, and monoamine metabolites in a single column with binary gradient. No other chemical reactions are necessary. In order to reduce the running time and yet achieve a reproducible retention time by the autosampler injection, our gradient elution profile was modified to produce a shorter equilibration time and to compensate for the initial contamination of mobile phase B following the first injection. Without the use of two columns in series and peak suppresser/gradient mixer, we have simplified the previously published method to measure over 20 different antioxidants, oxidative stress markers and monoamine metabolites simultaneously in biological samples. [source] Nitration and Increased ,-Synuclein Expression Associated With Dopaminergic Neurodegeneration In Equine Pituitary Pars Intermedia DysfunctionJOURNAL OF NEUROENDOCRINOLOGY, Issue 2 2005D. McFarlane Abstract Equine pituitary pars intermedia dysfunction (PPID) is a spontaneously occurring progressive disease affecting aged horses and ponies. The pathogenesis of PPID is poorly understood, but the available evidence supports a loss of dopaminergic inhibition of the melanotropes of the pars intermedia. Horses with PPID have increased plasma concentrations of pars intermedia pro-opiomelanocortin-derived peptides that decrease in response to dopamine or dopamine agonist administration. Dopamine and dopamine metabolite concentrations are decreased in the pars intermedia of affected horses compared to age-matched control horses. Horses with disease that are treated with the dopamine agonist pergolide show improvement in clinical signs and normalisation of diagnostic test results. In the present study, immunohistochemical evaluation of pituitary and hypothalamic tissue demonstrated reduced tyrosine hydroxylase immunoreactivity in affected horses compared to age-matched and young controls, supporting the role of dopaminergic neurodegeneration in PPID. In addition, immunohistochemical evaluation revealed an increase in the oxidative stress marker, 3-nitrotyrosine and in nerve terminal protein, ,-synuclein that colocalised in the pars intermedia of horses with disease. These findings suggest a role for nitration of overexpressed ,-synuclein in the pathogenesis of neurodegeneration in PPID. [source] Eviprostat suppresses urinary oxidative stress in a rabbit model of partial bladder outlet obstruction and in patients with benign prostatic hyperplasiaPHYTOTHERAPY RESEARCH, Issue 2 2010Seiji Matsumoto Abstract Eviprostat is a phytotherapeutic agent that has been used widely for more than 40 years in the treatment of benign prostatic hyperplasia (BPH) in Japan and Germany, and is known to have antioxidant activity. The present study investigated the effect of Eviprostat on the levels of the urinary oxidative stress marker 8-hydroxy-2,-deoxyguanosine (8-OHdG) in a rabbit model of surgical partial bladder outlet obstruction (PBOO) and in patients with lower urinary tract symptoms (LUTS) associated with BPH. In the rabbit model, 8-OHdG levels in urine collected after 3 weeks of PBOO were 3.8-fold higher than in the urine of sham-operated rabbits. When twice-daily Eviprostat was administered orally throughout the 3-week PBOO period, the increase in urinary 8-OHdG levels was suppressed by 70%. In the clinical study, nine patients who received Eviprostat for 4 weeks showed 2.5-fold lower urinary 8-OHdG levels than before treatment. During Eviprostat treatment, the total International Prostate Symptom Score (IPSS) decreased from 16.56 ± 2.74 to 13.67 ± 2.30 and the quality of life score from 4.22 ± 0.40 to 3.22 ± 0.46. The findings provide evidence that the antioxidant activity of Eviprostat is responsible for its beneficial effects in the treatment of BPH. Copyright © 2009 John Wiley & Sons, Ltd. [source] FK506 and Sildenafil Promote Erectile Function Recovery after Cavernous Nerve Injury Through Antioxidative MechanismsTHE JOURNAL OF SEXUAL MEDICINE, Issue 4i 2007Gwen Lagoda MS ABSTRACT Introduction., Immunophilin ligands and phosphodiesterase type 5 (PDE5) inhibitors are touted to promote erectile function recovery after cavernous nerve (CN) injury. However, the mechanisms for their effects remain unclear. Aim., To compare the erection recovery effects of the immunophilin ligand FK506 and the PDE5 inhibitor sildenafil after CN injury and determine whether they involve antioxidative and/or antiapoptotic mechanisms. Methods., Initial experiments established conditions of our CN injury model in adult male Sprague-Dawley rats. Subsequently, we evaluated treatment effects 14 days after: (i) unilateral CN injury (UNI) + saline (vehicle control); (ii) UNI + FK506 (5 mg/kg once daily, subcutaneous ×5 days); (iii) UNI + sildenafil (20 mg/kg every 8 hours, subcutaneous ×7 days); (iv) UNI + FK506/sildenafil; and (v) sham surgery. Main Outcome Measures., Intracavernous pressure (ICP) measurement after CN electrical stimulation to assess erectile function and Western blot analysis of expressions of glutathione peroxidase (GPX; antioxidant enzyme), nitrotyrosine (NT; oxidative stress marker), and phosphorylated and total Akt (antiapoptotic factor) in penes. Results., In the UNI model, GPX expression was increased at Days 1 and 7, while p-Akt expression decreased at Day 1 and returned to baseline at Day 7. GPX expression was significantly higher in the UNI + FK506 group compared with the saline-treated group (P < 0.05). ICP increased in all treatment groups compared with that of the saline-treated group (P < 0.05). NT levels were increased after saline treatment (P < 0.05) but not after FK506 and sildenafil treatment, alone or in combination. GPX was localized to nerves coursing through the penis and to smooth muscle and endothelium of the dorsal vein and arteries. Conclusions., Both FK506 and sildenafil protect erectile function after CN injury by decreasing oxidative stress-associated tissue damage. FK506 may act through increased GPX activity. Further research is required to elucidate mechanisms associated with the beneficial effect of sildenafil. Lagoda G, Jin L, Lehrfeld TJ, Liu T, and Burnett AL. FK506 and sildenafil promote erectile function recovery after cavernous nerve injury through antioxidative mechanisms. J Sex Med 2007;4:908,916. [source] Leptin-mediated neovascularization is a prerequisite for progression of nonalcoholic steatohepatitis in rats,HEPATOLOGY, Issue 4 2006Mitsuteru Kitade Nonalcoholic steatohepatitis (NASH) may cause fibrosis, cirrhosis, and hepatocellular carcinoma (HCC); however, the exact mechanism of disease progression is not fully understood. Angiogenesis has been shown to play an important role in the progression of chronic liver disease. The aim of this study was to elucidate the role of angiogenesis in the development of liver fibrosis and hepatocarcinogenesis in NASH. Zucker rats, which naturally develop leptin receptor mutations, and their lean littermate rats were fed a choline-deficient, amino acid,defined diet. Both Zucker and littermate rats showed marked steatohepatitis and elevation of oxidative stress markers (e.g., thiobarbital acid reactive substances and 8-hydroxydeoxyguanosine). In sharp contrast, liver fibrosis, glutathione- S -transferase placental form (GST-P)-positive preneoplastic lesions, and HCC developed in littermate rats but not in Zucker rats. Hepatic neovascularization and the expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, only increased in littermate rats, almost in parallel with fibrogenesis and carcinogenesis. The CD31-immunopositive neovessels were mainly localized either along the fibrotic septa or in the GST-P,positive lesions. Our in vitro study revealed that leptin exerted a proangiogenic activity in the presence of VEGF. In conclusion, these results suggest that leptin-mediated neovascularization coordinated with VEGF plays an important role in the development of liver fibrosis and hepatocarcinogenesis in NASH. (HEPATOLOGY 2006;44:983,991.) [source] Amelioration of Cadmium-Induced Oxidative Stress, Impairment in Lipids and Plasma Lipoproteins by the Combined Treatment with Quercetin and ,-Tocopherol in RatsJOURNAL OF FOOD SCIENCE, Issue 7 2010S. Milton Prabu Abstract:, Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and ,-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P < 0.05) increase in thiobarbituric acid reactive substances (TBARS), lipid hydro peroxides (LOOH), total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), free fatty acids (FFA), phospholipids (PL), triglycerides (TGs), and the activity of hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) in plasma with a significant (P > 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases. [source] Oxidative-inflammatory damage in cirrhosis: Effect of vitamin E and a fermented papaya preparationJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2007Francesco Marotta Abstract Background and Aim:, Oxidative DNA damage occurs as an early event in hepatitis C virus (HCV) infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in patients with HCV-related cirrhosis. Methods:, The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized food-vitamin composition assessment and were assessed for dietary intake, nutritional status and iron level. Patients were randomly allocated into two groups and then given either ,-tocopherol 900 IU/day or 9 g/day of a fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, redox status (reduced glutathione, glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma ,-tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA and serum levels of cytokines. Results:, Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (P < 0.005 vs controls). Neither treatment regimen affected transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin E treatment (P < 0.05). Conclusions:, Although the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease. [source] Poster Sessions AP13: Novel Techniques and TechnologiesJOURNAL OF NEUROCHEMISTRY, Issue 2002J. K. Yao Studies of the antioxidant defense system and the monoamine metabolic pathways are often complicated by cumbersome analytical methods, which require separate and multistep extraction and chemical reaction procedures. Thus, measurements of multiple parameters are limited in relatively small biological samples. High performance liquid chromatography (HPLC) coupled with a Coulometric Multi-Electrode Array System (CMEAS) provides us a convenient and most sensitive tool to measure low molecular weight, redox-active compounds in biological sample. The deproteinized sample was analyzed on a HPLC coupled with a 16-channel CMEAS, which incremented from 60 to 960 mV in 60 mV steps. Each sample was run on a single column (Meta-250, 4.6 × 250 mm) under a 150-minute complex gradient that ranged from 0% B (A: 1.1% pentane sulfonic acid) to 20% B (B: 0.1 m lithium acetate in mixture of methanol, acetonenitrile and isopropanol), with a flow rate of 0.5 mL/min. We have developed an automated procedure to simultaneously measure various antioxidant, oxidative stress marker, and monoamine metabolites in a single column with binary gradient. No other chemical reactions are necessary. In order to reduce the running time and yet achieve a reproducible retention time by the autosampler injection, our gradient elution profile was modified to produce a shorter equilibration time and to compensate for the initial contamination of mobile phase B following the first injection. Without the use of two columns in series and peak suppresser/gradient mixer, we have simplified the previously published method to measure over 20 different antioxidants, oxidative stress markers and monoamine metabolites simultaneously in biological samples. [source] Melatonin reduces uranium-induced nephrotoxicity in ratsJOURNAL OF PINEAL RESEARCH, Issue 1 2007Montserrat Bellés Abstract:, The protective role of exogenous melatonin on U-induced nephrotoxicity was investigated in rats. Animals were given single doses of uranyl acetate dihydrate (UAD) at 5 mg/kg (subcutaneous), melatonin at 10 or 20 mg/kg (intraperitoneal), and UAD (5 mg/kg) plus melatonin (10 or 20 mg/kg), or vehicle (control group). In comparison with the UAD-treated group only, significant beneficial changes were noted in some urinary and serum parameters of rats concurrently exposed to UAD and melatonin. The increase of U excretion after UAD administration was accompanied by a significant reduction in the renal content of U when melatonin was given at a dose of 20 mg/kg. Melatonin also reduced the severity of the U-induced histological alterations in kidney. In renal tissue, the activity of the superoxide dismutase (SOD) and the thiobarbituric acid reactive substances (TBARS) levels increased significantly as a result of UAD exposure. Following UAD administration, oxidative stress markers in erythrocytes showed a reduction in SOD activity and an increase in TBARS levels, which were significantly restored by melatonin administration. In plasma, reduced glutathione (GSH) and its oxidized form (GSSG) were also altered in UAD-exposed rats. However, only the GSSG/GSH ratio was restored to control levels after melatonin treatment. Oxidative damage was observed in kidneys. Melatonin administration partially restored these adverse effects. It is concluded that melatonin offers some benefit as a potential agent to treat acute U-induced nephrotoxicity. [source] Oxidative stress in developmental brain disordersNEUROPATHOLOGY, Issue 1 2009Masaharu Hayashi Oxidative stress is one of the predisposing factors in adult neurological disorders. We have examined the involvement of oxidative stress in child-onset neurodegenerative disorders, and here we review the findings from our analysis. In cases of Cockayne syndrome, the oxidative products of lipids and proteins were increased in the globus pallidus; however, oxidative nucleotide damage that coincided with reduced copper/zinc superoxide dismutase (Cu/ZnSOD) expression was observed in cases of xeroderma pigmentosum, and these patients also presented increased oxidative stress markers in urine samples. In spinal muscular atrophy, lipid peroxidation in conjunction with oxidative DNA damage was observed in motor neurons. Cases of subacute sclerosing panencephalitis presented oxidative nucleoside damage in cerebral cortical neurons at early disease stages, which were subsequently replaced by lipid peroxidation in glial cells of cerebral white matter. In relation to progressive myoclonic epilepsy, oxidative damage to DNA, proteins, and lipids appeared to coincide with cerebral and cerebellar cortical lesions of neuronal ceroid-lipofuscinosis. Patients with Lafora disease also presented an increase in oxidative stress markers for DNA and/or lipids in the brain and urine. These findings imply involvement of oxidative stress in developmental brain disorders; antioxidant agents could prove to be useful for treating patients with those disorders. [source] Urinary oxidative stress markers in young patients with type 1 diabetesPEDIATRICS INTERNATIONAL, Issue 1 2006IKUE HATA Abstract Background: Involvement of oxidative stress in the pathogenesis of diabetic vascular complications has been proposed. However, there are few methods to determine the status of oxidative stress both directly and quantitatively in young patients with type 1 diabetes. Methods: A total of 27 young patients with type 1 diabetes (mean age ± SD, 12.6 ± 4.2 years) with normal renal function and 38 healthy control subjects (13.0 ± 4.6 years) were investigated. Early morning voiding urine samples were collected. The concentrations of acrolein-lysine adducts, 8-hydroxy-2,-deoxyguanosine (8-OHdG) were determined using competitive enzyme-linked immunosorbent assay, and nitric oxide metabolites were measured using the colorimetric, non-enzymatic assay. Results: Urinary concentrations of 8-OHdG, but not acrolein-lysine adducts and nitric oxide metabolites, were significantly increased in the diabetic group. For diabetic patients, microalbuminuria was significantly correlated with higher concentrations of all three markers. Hemoglobin A1c values were significantly correlated with 8-OHdG values. Conclusions: These findings indicate that increased oxidative stress and the risk of vascular complications may be present at early stages of type 1 diabetes. [source] In Vivo Radioprotective Effects of Nigella sativa L Oil and Reduced Glutathione Against Irradiation-Induced Oxidative Injury and Number of Peripheral Blood Lymphocytes in RatsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2006Mustafa Cemek Radiotherapy is one of the most common therapies for treating human cancers. Several studies have indicated that irradiation induces reactive oxygen species (ROS), which play an important role in radiation damage of the cell. It has been shown that Nigella saliva L. (NS) and reduced glutathione (GSH) have both an antiperoxidative effect on different tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant and radio-protective roles of NS and GSH against irradiation-induced oxidative injury in an experimental model. The NS group was administrated NS (1 mL/kg body weight), the GSH group was injected GSH (150 mg/kg body weight) and the control group was given physiologic saline solution (1 mL/kg body weight) for 30 consecutive days before exposure to a single dose of 6 Gy of radiation. Animals were sacrificed after irradiation. Malondialdehyde, nitrate, nitrite (oxidative stress markers) and ascorbic acid, retinol, ,-carotene, GSH and ceruloplasmin (nonenzymatic antioxidant markers) levels and peripheral blood lymphocytes were measured in all groups. There were statistically significant differences between the groups for all parameters (P < 0.05). Whole-body irradiation caused a significant increase in blood malondialdehyde, nitrate and nitrite levels. The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, non-enzymatic antioxidant levels were significantly increased. Also, our results suggest that NS and GSH administration prior to irradiation prevent the number of alpha-naphthyl acetate esterase peripheral blood T lymphocytes from declining. These results clearly show that NS and GSH treatment significantly antagonize the effects of radiation. Therefore, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury. [source] Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic ratPHYTOTHERAPY RESEARCH, Issue 8 2010Tourandokht Baluchnejadmojarad Abstract The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)-diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM-treated control and diabetic, and sodium salisylate (SS)-treated control and diabetic. SM was administered daily at a dose of 100,mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising in patients on dialysis,THE JOURNAL OF PATHOLOGY, Issue 2 2007Y Hori Abstract Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis than in patients with normal renal function. However, the mechanism underlying carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that oxidative stress affects patients on dialysis and generates new neoplasms, and therefore analysed the correlation between the influences of various markers of oxidative stress and carcinogenesis in those patients. We evaluated the immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG, and COX-2 in 42 cases on dialysis and 51 cases with normal renal function as a control. The methylation status of p16INK4a, p14ARF, VHL, and RASSF1A was analysed together with clinicopathological factors. Histologically, the papillary type was observed more frequently in dialysis RCC than in sporadic RCC. Immunohistochemically, overexpression of iNOS (p < 0.0001) and COX-2 (p = 0.0002) was more frequently observed in dialysis RCC. Furthermore, the 8-OHdG labelling index was significantly higher in dialysis RCC than in sporadic RCC. Hypermethylation of p16INK4a was more frequently found in dialysis RCC (p < 0.05). However, no significant correlations between oxidative stress markers and DNA hypermethylation status were observed. The overexpression of iNOS, COX-2, and 8-OHdG in dialysis RCC suggests that patients on dialysis are affected by oxidative stress and that this effect plays an important role in the genesis of dialysis RCC. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Effect of high environmental temperatures on ascorbic acid, sulfhydryl residue and oxidized lipid concentrations in plasma of dairy cowsANIMAL SCIENCE JOURNAL, Issue 3 2007Masahito TANAKA ABSTRACT Information on oxidative stress under hot conditions from the levels of cells to organs and the whole body has accumulated in the last decades. Although a hot climate decreased dairy performance, changes of oxidative stress markers under hot conditions have remained obscure. Therefore, the effect of high environmental temperature on ascorbic acid, sulfhydryl (SH) residue and oxidized lipids concentrations in plasma from a total of 128 dairy cows was investigated. The monthly average maximum day temperature varied from 9.2°C in January to 32°C in August of 2004 in this institute. High ambient temperatures increased the rectal temperature of dairy cows up to 39.3°C in August. One of the reducing equivalents in plasma, SH residue concentration, decreased in July compared with December (P < 0.05). Another antiradical molecule, ascorbic acid concentration in plasma, also decreased in July (P < 0.01). The oxidative stress index, thiobarbituric acid reactive substance (TBARS), which was produced from the oxidation of polyunsaturated fatty acids under oxidative conditions, increased in summer (P < 0.05). A significant positive relationship of SH residue and ascorbic acid concentrations in the hot season was observed (P < 0.01). A negative correlation between rectal temperatures and ascorbic acid concentrations in the hot season was obtained (P < 0.01). However, TBARS concentration varied independently of the SH residue and ascorbic acid concentration. These results suggest that the response of oxidative stress markers of SH residue, ascorbic acid and TBARS concentration to oxidative stress under hot conditions were not shown to be the same, and that oxidative stress in dairy cows in the hot season increased. [source] Oxidative stress in SEPN1 -related myopathy: From pathophysiology to treatment,ANNALS OF NEUROLOGY, Issue 6 2009Sandrine Arbogast PhD Objective Mutations of the selenoprotein N gene (SEPN1) cause SEPN1 -related myopathy (SEPN1-RM), a novel early-onset muscle disorder formerly divided into four different nosological categories. Selenoprotein N (SelN) is the only selenoprotein involved in a genetic disease; its function being unknown, no treatment is available for this potentially lethal disorder. Our objective was to clarify the role of SelN and the pathophysiology of SEPN1-RM to identify therapeutic targets. Methods We established and analyzed an ex vivo model of SelN deficiency using fibroblast and myoblast primary cultures from patients with null SEPN1 mutations. DCFH assay, OxyBlot, Western blot, Fura-2, and cell survival studies were performed to measure intracellular oxidant activity, oxidative stress markers, calcium handling, and response to exogenous treatments. Results SelN-depleted cells showed oxidative/nitrosative stress manifested by increased intracellular oxidant activity (reactive oxygen species and nitric oxide) and/or excessive oxidation of proteins, including the contractile proteins actin and myosin heavy chain II in myotubes. SelN-devoid myotubes showed also Ca2+ homeostasis abnormalities suggesting dysfunction of the redox-sensor Ca2+ channel ryanodine receptor type 1. Furthermore, absence of SelN was associated with abnormal susceptibility to H2O2 -induced oxidative stress, demonstrated by increased cell death. This cell phenotype was restored by pretreatment with the antioxidant N-acetylcysteine. Interpretation SelN plays a key role in redox homeostasis and human cell protection against oxidative stress. Oxidative/nitrosative stress is a primary pathogenic mechanism in SEPN1-RM, which can be effectively targeted ex vivo by antioxidants. These findings pave the way to SEPN1-RM treatment, which would represent a first specific pharmacological treatment for a congenital myopathy. Ann Neurol 2009;65:677,686 [source] Glutathione peroxidase activity modulates recovery in the injured immature brain,ANNALS OF NEUROLOGY, Issue 5 2009Kyoko Tsuru-Aoyagi MD Objective Mice subjected to traumatic brain injury at postnatal day 21 show emerging cognitive deficits that coincide with hippocampal neuronal loss. Here we consider glutathione peroxidase (GPx) activity as a determinant of recovery in the injured immature brain. Methods Wild-type and transgenic (GPxTg) mice overexpressing GPx were subjected to traumatic brain injury or sham surgery at postnatal day 21. Animals were killed acutely (3 or 24 hours after injury) to assess oxidative stress and cell injury in the hippocampus or 4 months after injury after behavioral assessments. Results In the acutely injured brains, a reduction in oxidative stress markers including nitrotyrosine was seen in the injured GPxTg group relative to wild-type control mice. In contrast, cell injury, with marked vulnerability in the dentate gyrus, was apparent despite no differences between genotypes. Magnetic resonance imaging demonstrated an emerging cortical lesion during brain maturation that was also indistinguishable between injured genotypes. Stereological analyses of cortical volumes likewise confirmed no genotypic differences between injured groups. However, behavioral tests beginning 3 months after injury demonstrated improved spatial memory learning in the GPxTg group. Moreover, stereological analysis within hippocampal subregions demonstrated a significantly greater number of neurons within the dentate of the GPx group. Interpretation Our results implicate GPx in recovery of spatial memory after traumatic brain injury. This recovery may be attributed, in part, to a reduction in early oxidative stress and selective, long-term sparing of neurons in the dentate. Ann Neurol 2009;65:540,549 [source] The effects of dietary organic or inorganic selenium in rainbow trout (Oncorhynchus mykiss) under crowding conditionsAQUACULTURE NUTRITION, Issue 6 2009F.Z. KÜÇÜKBAY Abstract In the present study, the effects of different sources of selenium (Se; sodium selenite or selenomethionine) supplementation on the growth and serum concentrations of oxidative stress markers [malondialdehyde (MDA), 8-isoprostane, glutathione peroxidase (GSH-Px) activity] and muscle Se, MDA and heat shock protein 70 (Hsp70) levels in rainbow trouts were evaluated. The fish (n = 360; 0 + years old) with initial average weight of 20 ± 0.8 g were randomly assigned to 12 treatment groups consisting of 3 replicates of 10 fish each in a 2 × 2 × 3 factorial arrangement of treatments (stocking densities, Se sources, Se levels). The fish were kept at low (25 kg m,3) or high (100 kg m,3) stocking densities and fed a basal (control) diet or the basal diet supplemented with either 0.15 or 0.30 mg of Se kg,1 of diet from two different forms: sodium selenite or selenomethionine. High stocking density decreased weight gain, feed intake and feed conversion ratio (FCR) when basal diet was fed (P = 0.001). A linear increase in feed intake and weight gain and improvement in FCR were found in sodium selenite (P = 0.01)- or selenomethionine (P = 0.001)-supplemented fish reared under crowding conditions. Serum and muscle Se levels and serum GSH-Px activity increased (P = 0.001) linearly, whereas serum and muscle MDA concentrations and serum 8-isoprostane decreased linearly as dietary sodium selenite (P = 0.01) or selenomethionine (P = 0.001) supplementation increased. Selenomethionine and sodium selenite supplementation decreased Hsp70 in the muscle of fish reared under crowding conditions (P < 0.05). Supplementation with Se improved growth and antioxidant status of fish and the effects of selenomethionine were relatively greater than sodium selenite in the crowded groups. Results suggest that crowding conditions cause significant detrimental effects in rainbow trout indicated by increased oxidative stress, reduced feed intake and body weight gain. ,t also indicates that dietary Se supplementation offers a feasible way of reducing the losses in performance of rainbow trout reared under crowding conditions. Selenomethionine seems to be more effective than sodium selenite and the higer dose in the present study also seems to be more effective than the lower dose. [source] Lycopene, a Carotenoid, Attenuates Cyclosporine-Induced Renal Dysfunction and Oxidative Stress in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2007Ahmet Ate, ahin Adult male Sprague-Dawley rats were randomly divided into four groups. The control group received physiological saline; animals in the lycopene group received only lycopene (10 mg/kg); animals in the cyclosporine A group received only cyclosporine A (15 mg/kg) and animals in cyclosporine plus lycopene group received cyclosporine and lycopene for 21 days. The effects of lycopene on cyclosporine A-induced nephrotoxicity were evaluated by plasma creatinine, urea, sodium and calcium concentrations; kidney tissue thiobarbituric acid reactive species, reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and catalase activities and histopatological examinations. Administration of cyclosporine A to rats induced a marked renal failure, characterized with a significant increase in plasma creatinine and urea concentrations. Cyclosporine A also induced oxidative stress as indicated by increased kidney tissue concentrations of thiobarbituric acid reactive species and GSH, and reduced activities of GSH-Px and catalase. Moreover, the kidneys of cyclosporine A-treated rats showed tubular necrosis, degeneration, dilatation, thickened basement membranes, luminal cast formation and inter-tubular fibrosis. Lycopene markedly reduced elevated plasma creatinine, urea levels and counteracted the deleterious effects of cyclosporine A on oxidative stress markers. In addition, lycopene ameliorated cyclosporine A-induced pathological changes including tubular necrosis, degeneration, thickened basement membranes and inter-tubular fibrosis when compared to the alone cyclosporine A group. These data indicate that the natural antioxidant lycopene might have protective effect against cyclosporine-induced nephrotoxicity and oxidative stress in rat. [source] The assessment of oxidative stress in infertile patients with varicoceleBJU INTERNATIONAL, Issue 12 2008Yuichi Sakamoto OBJECTIVES To assess oxidative stress markers, antioxidant capacity and cytokines in seminal plasma from infertile patients with varicocele, and to investigate seminal oxidative status and sperm DNA damage after varicocelectomy. PATIENTS, SUBJECTS AND METHODS The records were retrospectively evaluated for 28 azoospermic, 30 oligospermic (15 with varicocele and 15 without) and 30 patients with normal semen characteristics (15 with varicocele and 15 without). The mean (sd) age of the men was 32.4 (5.6) years; all men with varicocele had a unilateral or bilateral microsurgical subinguinal varicocelectomy. The level of nitric oxide (NO), 8-hydroxy-2,-deoxyguanosine (8-OHdG), hexanoyl-lysine (HEL), superoxide dismutase (SOD) activity, interleukin (IL)-6, IL-8 and tumour necrosis factor-, in seminal plasma were measured. In addition, sperm DNA fragmentation was analysed before and 6 months after varicocelectomy. RESULTS Azoospermic and oligospermic patients had a significantly higher HEL concentration and SOD activity in seminal plasma; those with varicocele had a significantly higher NO, HEL, and SOD activity in seminal plasma. There was a significant increase in sperm concentration and reduction in NO, HEL, 8-OHdG level and SOD activity after varicocelectomy. Oligospermic patients with varicocele had a significantly higher IL-6 level in seminal plasma, and there was a significant reduction after varicocelectomy. The percentage of apoptosis-positive sperm decreased significantly after varicocelectomy. CONCLUSIONS This study indicates that the seminal plasma of patients with varicocele is under excessive oxidative stress, and partly even in patients with normospermia, and that varicocelectomy reduces oxidative stress in seminal plasma and ameliorates sperm DNA damage. [source] Cerebrospinal fluid, serum and plasma protein oxidation in Alzheimer's diseaseACTA NEUROLOGICA SCANDINAVICA, Issue 1 2009M. A. Korolainen Objectives,,, Many studies have shown differences in carbonylation and nitration of individual proteins in brain and body fluids of Alzheimer's disease (AD) patients. Therefore, we wanted to examine whether total levels of these oxidative stress markers of proteins were altered in AD. Patients and methods,,, Total levels of carbonyls and nitrotyrosine in cerebrospinal fluid, serum and plasma were measured in 22 AD patients and 18 age-matched controls using commercially available enzyme immunoassay kits. Results,,, Protein carbonylation in cerebrospinal fluid did not differ between AD patients and controls but was decreased in APOE ,4 carriers as compared with non-carriers. Serum but not plasma levels of carbonyls tended to be decreased in AD patients as compared with aged controls. Nitrotyrosine concentrations did not differ between the groups. Surrogate cerebrospinal fluid markers for AD, beta-amyloid (1,42) and tau, correlated with blood carbonyl and nitrotyrosine levels. Conclusions,,, According to these preliminary data, changes in oxidative metabolism related to the pathogenesis of AD cannot be detected as increased cerebrospinal fluid, serum or plasma protein carbonylation or nitration. [source] A central role of eNOS in the protective effect of wine against metabolic syndromeCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2006Federico Leighton Abstract The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10,30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic syndrome. This hypothesis is supported by epidemiological observations and needs experimental validation in human intervention studies. Copyright © 2005 John Wiley & Sons, Ltd. [source] 3353: Response of the human eye against oxidative stress at high altitudesACTA OPHTHALMOLOGICA, Issue 2010S KARAKUCUK Purpose To evaluate the response of the anterior segment of the eye against oxidative stress during acute exposure to high altitudes. Methods Forty volunteers were examined and measurements performed at Erciyes University Medical Faculty,Ophthalmology Clinic, Kayseri,Turkey(1080m). On the following day, participants were transported to Mt. Erciyes Ski Center by bus(2200m); thereafter they climbed to an altitude of 2800m.with a moderate pace. Central corneal thickness, intraocular pressure,spheric equivalent of refraction, arterial oxygen pressure,blood pressure, pulse rate and body temperature were measured at both altitudes. Venous blood samples were taken from volunteers at both altitudes;total oxidant status (TOS),total antioxidant status(TAS),advanced oxidation protein products (AOPP), xanthine oxidase (XO), thiol, adenosine deaminase(ADA)levels were investigated at 1080m and 2800m. Results TOS(7.02µmol H2O2 equiv/L, range:0.49-22.07) and AOPP(220.74µmol/L,range:103.81-667.35)significantly increased at high altitude, compared to low altitude levels (3.32µmol H2O2 equiv/L range:0.92-18.41,and 195.58µmol/L,range:84.77-663.16, resp; p<0.05).IOP significantly elevated at high altitude (14.45±3.54mmHg vs 13.22±2.74mmHg; p<0.05). There was a significant positive correlation between IOP and TAS levels(p<0.05). No significant correlation was found between spherical equivalent or central corneal thickness with the investigated oxidation parameters at both altitudes Conclusion We conclude that oxidative stress markers, TOS and AOPP are increased along with IOP during acute exposure to hypoxic environment at high altitudes and that antioxidant system may have a limited capacity to counter balance this effect because of acute unacclimatized ascent. [source] Antioxidant capacity of human milk: effect of thermal conditions for the pasteurizationACTA PAEDIATRICA, Issue 8 2008Dolores Silvestre Abstract Aim: Pasteurization is the thermal treatment usually applied in milk banks to eliminate the risk of transmission of infectious agents. The aim of this study was to investigate the effect of heat processing upon the antioxidant properties of human milk. Methods: Milk samples collected from 31 healthy women were subjected to two different pasteurization techniques: Holder pasteurization (63°C for 30 min) and high pasteurization (75°C for 15 sec) and oxidative stress markers (glutathione, glutathione peroxidase activity, malondialdehyde and total antioxidant capacity) were determined in comparison to fresh milk. Results: Malondialdehyde concentration was the same in all samples, while there was a decrease in glutathione concentration and total antioxidant capacity in milk samples subjected to thermal processing versus fresh milk samples. However, the drop in these parameters was seen to be significantly greater when applying Holder pasteurization. Both thermal treatments induced considerable and similar loss of glutathione peroxidase activity. Conclusion: Thermal processing of human milk implies a decrease in its antioxidant properties but, when necessary, high pasteurization should be the election method in terms of milk oxidative status. [source] INCREASED SYSTEMIC OXIDATIVE AND NITRATIVE STRESS IN A NEW CONGENIC MODEL OF METABOLIC SYNDROME DERIVED FROM STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS AND ZUCKER FATTY RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 2007Yu Yamaguchi SUMMARY 1Oxidative stress has been recognized as an important factor in the biology of lifestyle-related diseases. Systemic oxidative stress may increase in metabolic syndrome characterized by a cluster of metabolic risk factors. To confirm this hypothesis, we investigated systemic oxidative/nitrative stress in a new congenic model of metabolic syndrome, namely SHRSP/ZF rats, which are derived from stroke-prone spontaneously hypertensive (SHRSP) and Zucker fatty (Zucker) rats. 2The SHRSP/ZF rats display obesity, hypertension, hyperlipidaemia, hyperglycaemia and glucose intolerance. At 6 weeks of age, SHRSP/ZF rats already showed increases in serum levels of thiobarbituric acid-reactive substances (TBARS) and oxidatively modified low-density lipoprotein (Ox-LDL) compared with lean SHRSP littermates and Zucker rats, whereas serum levels of 8-hydroxy-2,-deoxyguanine (8-OHdG), 3-nitrotyrosine, 3-chlorotyrosine and high-sensitivity C-reactive protein (hsCRP), an inflammatory marker, did not differ significantly among the three rat strains. However, levels of these oxidative/nirative stress markers in SHRSP/ZF rats, as well as in SHRSP, increased gradually with age. After 36 weeks of age, the levels of TBARS, 8-OHdG, 3-nitrotyrosine and hsCRP in SHRSP/ZF rats increased rapidly and three of six rats died thereafter. Increased oxidative/nitrative stress may be associated with death in these rats. 3Our findings indicate that systemic oxidative/nitrative stress is evidently increased in metabolic syndrome. [source] Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity,ARTHRITIS & RHEUMATISM, Issue 7 2010Gangduo Wang Objective Free radical,mediated reactions have been implicated as contributors in a number of autoimmune diseases, including systemic lupus erythematosus (SLE). However, the potential for oxidative/nitrosative stress to elicit an autoimmune response or to contribute to disease pathogenesis, and thus be useful when determining a prognosis, remains largely unexplored in humans. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with SLE. Methods Sera from 72 SLE patients with varying levels of disease activity according to the SLE Disease Activity Index (SLEDAI) and 36 age- and sex-matched healthy controls were evaluated for serum levels of oxidative/nitrosative stress markers, including antibodies to malondialdehyde (anti-MDA) protein adducts and to 4-hydroxynonenal (anti-HNE) protein adducts, MDA/HNE protein adducts, superoxide dismutase (SOD), nitrotyrosine (NT), and inducible nitric oxide synthase (iNOS). Results Serum analysis showed significantly higher levels of both anti,MDA/anti,HNE protein adduct antibodies and MDA/HNE protein adducts in SLE patients compared with healthy controls. Interestingly, not only was there an increased number of subjects positive for anti-MDA or anti-HNE antibodies, but also the levels of both of these antibodies were statistically significantly higher among SLE patients whose SLEDAI scores were ,6 as compared with SLE patients with lower SLEDAI scores (SLEDAI score <6). In addition, a significant correlation was observed between the levels of anti-MDA or anti-HNE antibodies and the SLEDAI score (r = 0.734 and r = 0.647, respectively), suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD and higher levels of iNOS and NT compared with healthy control sera. Conclusion These findings support an association between oxidative/nitrosative stress and SLE. The stronger response observed in serum samples from patients with higher SLEDAI scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis. [source] 4-Hydroxynonenal: A membrane lipid oxidation product of medicinal interestMEDICINAL RESEARCH REVIEWS, Issue 4 2008G. Poli Abstract A comprehensive focus on 4-hydroxynonenal (HNE) as candidate molecule in a variety of pathophysiological conditions occurring in humans is here provided. Despite an active, now well characterized, metabolism in most cells and tissues, HNE can be easily detected and quantified by means of several methods, although with different sensitivity. Measurements of HNE and/or stable metabolites in biological fluids are already applied as lipid peroxidation/oxidative stress markers in a huge number of human disease processes, often sustained by inflammatory reactions. A primary involvement of this aldehydic product of membrane lipid oxidation in inflammation-related events, as well as in regulation of cell proliferation and growth, in necrotic or apoptotic cell death, appears supported by its marked ability to modulate several major pathways of cell signaling and, consequently, gene expression. The actual knowledge of HNE reactivity, metabolism, signaling and modulatory effect in the various human organs should provide a solid background to the investigation of the aldehyde's contribution to the pathogenesis of human major chronic diseases and would likely promote advanced and oriented applications not only in diagnosis and prevention but also in molecular treatment of human diseases. © 2007 Wiley Periodicals, Inc. Med Res Rev, 28, No. 4, 569,631, 2008 [source] | ||||||||||||||||||||||||||||||||||