4-hydroxy-2-nonenal and Chronic-Disease

Reactive oxygen intermediates (ROI) and other pro-oxidant agents are known to elicit, in vivo and in vitro, oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids of membrane phospholipids (i.e, lipid peroxidation). This leads to the formation of a complex mixture of aldehydic end-products, including malonyldialdehyde (MDA), 4-hydroxy-2,3-nonenal (HNE), and other 4-hydroxy-2,3-alkenals (HAKs) of different chain length. These aldehydic molecules have been considered originally as ultimate mediators of toxic effects elicited by oxidative stress occurring in biological material. Experimental and clinical evidence coming from different laboratories now suggests that HNE and HAKs can also act as bioactive molecules in either physiological and pathological conditions. These aldehydic compounds can affect and modulate, at very low and nontoxic concentrations, several cell functions, including signal transduction, gene expression, cell proliferation, and, more generally, the response of the target cell(s). In this review article, we would like to offer an up-to-date review on this particular aspect of oxidative stress--dependent modulation of cellular functions-as well as to offer comments on the related pathophysiological implications, with special reference to human conditions of disease.

Topics: Aldehydes; Arteriosclerosis; Chemotactic Factors; Chronic Disease; Humans; Inflammation; Liver Diseases; Nervous System Diseases; Oxidative Stress; Proteins; Reperfusion Injury; Signal Transduction

Vascular dementia (VaD) is a progressive cognitive impairment caused by a reduced blood supply to the brain. Chronic cerebral hypoperfusion (CCH) is one cause of VaD; it induces oxidative stress, neuroinflammation, and blood-brain barrier (BBB) disruption, damaging several brain regions. Vitamin C plays a vital role in preventing oxidative stress-related diseases induced by reactive oxygen species, but it is easily oxidized and loses its antioxidant activity. To overcome this weakness, we have developed a vitamin C/DNA aptamer complex (NXP031) that increases vitamin C's antioxidant efficacy. Aptamers are short single-stranded nucleic acid polymers (DNA or RNA) that can interact with their corresponding target with high affinity. We established an animal model of VaD by permanent bilateral common carotid artery occlusion (BCCAO) in 12 week old Wistar rats. Twelve weeks after BCCAO, we injected NXP031 into the rats intraperitoneally for two weeks at moderate (200 mg/4 mg/kg) and high concentrations (200 mg/20 mg/kg). NXP031 administration alleviates cognitive impairment, microglial activity, and oxidative stress after CCH. NXP031 increased the expression of basal lamina (laminin), endothelial cell (RECA-1, PECAM-1), and pericyte (PDGFRβ); these markers maintain the BBB integrity. We found that NXP031 administration activated the Nrf2-ARE pathway and increased the expression of SOD-1 and GSTO1/2. These results suggest that this new aptamer complex, NXP031, could be a therapeutic intervention in CCH-induced VaD.

Topics: Aldehydes; Animals; Blood-Brain Barrier; Brain; Chronic Disease; Cognitive Dysfunction; Dementia, Vascular; Disease Models, Animal; Hippocampus; Male; Microglia; Microvessels; NF-E2-Related Factor 2; Rats, Wistar; Signal Transduction; Up-Regulation

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase produces reactive oxygen species (ROS) involved in oxidative stress and signal transduction. Recent studies have suggested that NADPH oxidase is associated with the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). The aim of this study was to detect the expression of NADPH oxidase subunits and 4-hydroxynonenal (4-HNE) in nasal polyp tissue and normal nasal mucosa, in order to explore the possible role played by NADPH oxidase in the pathogenesis of CRSwNP.. Thirteen patients with CRSwNP and 9 normal control subjects were selected to participate in this study, in which we evaluated the expression of different NADPH oxidase subunits (gp91. Western blot and real-time PCR results showed that p67. The levels of p67

Topics: Adult; Aged; Aldehydes; Chronic Disease; Eosinophils; Female; Humans; Male; Middle Aged; NADPH Oxidases; Nasal Mucosa; Nasal Polyps; Neutrophils; Oxidative Stress; Phosphoproteins; Rhinitis; Sinusitis

Chronic ethanol-mediated oxidative stress and lipid peroxidation increases the levels of various reactive lipid species including 4-hydroxynonenal (4-HNE), which can subsequently modify proteins in the liver. It has been proposed that 4-HNE modification adversely affects the structure and/or function of mitochondrial proteins, thereby impairing mitochondrial metabolism. To determine whether chronic ethanol consumption increases levels of 4-HNE modified proteins in mitochondria, male rats were fed control and ethanol-containing diets for 5 weeks and mitochondrial samples were analyzed using complementary proteomic methods. Five protein bands (approx. 35, 45, 50, 70, and 90kDa) showed strong immunoreactivity for 4-HNE modified proteins in liver mitochondria from control and ethanol-fed rats when proteins were separated by standard 1D SDS-PAGE. Using high-resolution proteomic methods (2D IEF/SDS-PAGE and BN-PAGE) we identified several mitochondrial proteins immunoreactive for 4-HNE, which included mitofilin, dimethylglycine dehydrogenase, choline dehydrogenase, electron transfer flavoprotein α, cytochrome c1, enoyl CoA hydratase, and cytochrome c. The electron transfer flavoprotein α consistently showed increased 4-HNE immunoreactivity in mitochondria from ethanol-fed rats as compared to mitochondria from the control group. Increased 4-HNE reactivity was also detected for dimethylglycine dehydrogenase, enoyl CoA hydratase, and cytochrome c in ethanol samples when mitochondria were analyzed by BN-PAGE. In summary, this work identifies new targets of 4-HNE modification in mitochondria and provides useful information needed to better understand the molecular mechanisms underpinning chronic ethanol-induced mitochondrial dysfunction and liver injury.

Topics: Aldehydes; Animals; Chronic Disease; Ethanol; Liver Diseases, Alcoholic; Male; Mitochondria, Liver; Mitochondrial Proteins; Protein Processing, Post-Translational; Proteomics; Rats; Rats, Sprague-Dawley

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.

Topics: Adolescent; Adult; Aldehydes; Antioxidants; Case-Control Studies; Child; Chronic Disease; Female; Humans; Lipid Peroxidation; Male; Nitric Oxide; Otitis Media; Oxidants; Oxidation-Reduction; Oxidative Stress; Peroxidase; Young Adult

The pathogenesis of cervical spondylotic myelopathy (CSM) is related to both primary mechanical and secondary biological injury. The authors of this study explored a novel, noninvasive method of promoting neuroprotection in myelopathy by using curcumin to minimize oxidative cellular injury and the capacity of omega-3 fatty acids to support membrane structure and improve neurotransmission.. An animal model of CSM was created using a nonresorbable expandable polymer placed in the thoracic epidural space, which induced delayed myelopathy. Animals that underwent placement of the expandable polymer were exposed to either a diet rich in docosahexaenoic acid and curcumin (DHA-Cur) or a standard Western diet (WD). Twenty-seven animals underwent serial gait testing, and spinal cord molecular assessments were performed after the 6-week study period.. At the conclusion of the study period, gait analysis revealed significantly worse function in the WD group than in the DHA-Cur group. Levels of brain-derived neurotrophic factor (BDNF), syntaxin-3, and 4-hydroxynonenal (4-HNE) were measured in the thoracic region affected by compression and lumbar enlargement. Results showed that BDNF levels in the DHA-Cur group were not significantly different from those in the intact animals but were significantly greater than in the WD group. Significantly higher lumbar enlargement syntaxin-3 in the DHA-Cur animals combined with a reduction in lipid peroxidation (4-HNE) indicated a possible healing effect on the plasma membrane.. Data in this study demonstrated that DHA-Cur can promote spinal cord neuroprotection and neutralize the clinical and biochemical effects of myelopathy.

Topics: Aldehydes; Animals; Brain-Derived Neurotrophic Factor; Chronic Disease; Curcuma; Diet; Disease Models, Animal; Docosahexaenoic Acids; Male; Neuroprotective Agents; Qa-SNARE Proteins; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on growth and the cardiovascular system. Glucocorticoid excess promotes free radical overproduction and vascular dysfunction.. We hypothesized that the adverse effects of postnatal glucocorticoid therapy are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects.. Male rat pups received a clinically relevant course of dexamethasone (Dex), or Dex with vitamins C and E (DexCE), on postnatal days 1-6 (P1-6). Controls received saline (Ctrl) or saline with vitamins (CtrlCE).. At P21, Dex reduced survival (Ctrl: 96 vs. Dex: 70%) and promoted asymmetric growth restriction (ponderal index, Ctrl: 6.3 +/- 0.1 g . mm(-3) x 10(-5) vs. Dex: 7.4 +/- 0.2 g . mm(-3) x 10(-5)), both p < 0.05. Dex increased cardiac oxidative stress (protein expression: 4-HNE +20%, Hsp90 -42% and eNOS -54%), induced left ventricle (LV) wall thinning (LV wall volume: Ctrl: 47.2 +/- 1.2 mm(3) vs. Dex: 38.9 +/- 1.7 mm(3)) and decreased the ratio of the aortic lumen:total vessel area (Ctrl: 0.74 +/- 0.01 vs. Dex: 0.66 +/- 0.02), all p < 0.05. DexCE restored towards control values survival, growth symmetry the aortic lumen:total vessel area, and increased the cardiac expression of Hsp90 relative to Dex. In addition, relative to controls, the decrease in the cardiac expression of eNOS was no longer significant in DexCE animals (-20.3 +/- 14.4%, p > 0.05). However, DexCE did not prevent growth retardation, cardiac 4-HNE upregulation (DexCE: +29%) or LV thinning (DexCE: 40.1 +/- 1.1 mm(3)). Treatment of neonates with vitamins alone affected somatic growth and promoted thinner LV walls (CtrlCE: 39.9 +/- 0.5 mm(3), p < 0.05).. Combined glucocorticoid and antioxidant therapy in premature infants may be safer than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.

Topics: Aldehydes; Animals; Animals, Newborn; Antioxidants; Ascorbic Acid; Cardiovascular Diseases; Chronic Disease; Dexamethasone; Drug Therapy, Combination; Glucocorticoids; Heart; HSP90 Heat-Shock Proteins; Lung Diseases; Male; Nitric Oxide Synthase Type III; Oxidative Stress; Rats; Vitamin E

A dyshomeostasis of extra- and intracellular Ca(2+) and Zn(2+) occurs in rats receiving chronic aldosterone/salt treatment (ALDOST). Herein, we hypothesized that the dyshomeostasis of intracellular Ca(2+) and Zn(2+) is intrinsically coupled that alters the redox state of cardiac myocytes and mitochondria, with Ca(2+) serving as a pro-oxidant and Zn(2+) as an antioxidant. Toward this end, we harvested hearts from rats receiving 4 weeks of ALDOST alone or cotreatment with either spironolactone (Spiro), an aldosterone receptor antagonist, or amlodipine (Amlod), an L-type Ca(2+) channel blocker, and from age/sex-matched untreated controls. In each group, we monitored cardiomyocyte [Ca(2+)]i and [Zn(2+)]i and mitochondrial [Ca(2+)]m and [Zn(2+)]m; biomarkers of oxidative stress and antioxidant defenses; expression of Zn transporters, Zip1 and ZnT-1; metallothionein-1, a Zn(2+)-binding protein; and metal response element transcription factor-1, a [Zn(2+)]i sensor and regulator of antioxidant defenses. Compared with controls, at 4-week ALDOST, we found the following: (a) increased [Ca(2+)]i and [Zn(2+)]i, together with increased [Ca(2+)]m and [Zn(2+)]m, each of which could be prevented by Spiro and attenuated with Amlod; (b) increased levels of 3-nitrotyrosine and 4-hydroxy-2-nonenal in cardiomyocytes, together with increased H(2)O(2) production, malondialdehyde, and oxidized glutathione in mitochondria that were coincident with increased activities of Cu/Zn superoxide dismutase and glutathione peroxidase; and (c) increased expression of metallothionein-1, Zip1 and ZnT-1, and metal response element transcription factor-1, attenuated by Spiro. Thus, an intrinsically coupled dyshomeostasis of intracellular Ca(2+) and Zn(2+) occurs in cardiac myocytes and mitochondria in rats receiving ALDOST, where it serves to alter their redox state through a respective induction of oxidative stress and generation of antioxidant defenses. The importance of therapeutic strategies that can uncouple these two divalent cations and modulate their ratio in favor of sustained antioxidant defenses is therefore suggested.

Topics: Aldehydes; Aldosterone; Amlodipine; Animals; Calcium; Calcium Channel Blockers; Chronic Disease; Disease Models, Animal; Glutathione Peroxidase; Homeostasis; Hydrogen Peroxide; Hyperaldosteronism; Male; Metallothionein; Mineralocorticoid Receptor Antagonists; Mitochondria, Heart; Myocytes, Cardiac; Oxidative Stress; Rats; Rats, Sprague-Dawley; Spironolactone; Superoxide Dismutase; Tyrosine; Zinc

A myopathy characterized by mitochondrial pathology and oxidative stress is present in patients with peripheral arterial disease (PAD). Patients with PAD differ in disease severity, mode of presentation, and presence of comorbid conditions. In this study, we used a mouse model of hindlimb ischemia to isolate and directly investigate the effects of chronic inflow arterial occlusion on skeletal muscle microanatomy, mitochondrial function and expression, and oxidative stress. Hindlimb ischemia was induced by staged ligation/division of the common femoral and iliac arteries in C57BL/6 mice, and muscles were harvested 12 wk later. Muscle microanatomy was examined by bright-field microscopy, and mitochondrial content was determined as citrate synthase activity in muscle homogenates and ATP synthase expression by fluorescence microscopy. Electron transport chain (ETC) complexes I through IV were analyzed individually by respirometry. Oxidative stress was assessed as total protein carbonyls and 4-hydroxy-2-nonenal (HNE) adducts and altered expression and activity of manganese superoxide dismutase (MnSOD). Ischemic muscle exhibited histological features of myopathy and increased mitochondrial content compared with control muscle. Complex-dependent respiration was significantly reduced for ETC complexes I, III, and IV in ischemic muscle. Protein carbonyls, HNE adducts, and MnSOD expression were significantly increased in ischemic muscle. MnSOD activity was not significantly changed, suggesting MnSOD inactivation. Using a mouse model, we have demonstrated for the first time that inflow arterial occlusion alone, i.e., in the absence of other comorbid conditions, causes myopathy with mitochondrial dysfunction and increased oxidative stress, recapitulating the muscle pathology of PAD patients.

Topics: Aldehydes; Animals; ATP Synthetase Complexes; Chronic Disease; Citrate (si)-Synthase; Female; Gene Expression Regulation; Hindlimb; Humans; Ischemia; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Muscle, Skeletal; Muscular Diseases; Oxidative Stress; Superoxide Dismutase

Alzheimer's disease is a progressive neurodegenerative disorder characterised by abnormal extracellular deposition of a 4 kDa peptide termed beta-amyloid, neuronal loss, oxidative stress and chronic astrocytosis and microgliosis, but how the latter two features contribute to the progression of the disease is poorly understood. We have previously demonstrated in a novel in vivo transplantation model that chronic astro- and microgliosis resulted in molecular pathology similar to that observed in the Alzheimer's disease brain. We now report that these heterotopic, gliotic transplants exhibit prolonged oxidative stress, characterised by lipid peroxidation and protein carbonyl formation. Furthermore, we demonstrate that dietary additives can elevate endogenous anti-oxidant defences and reduce oxidative stress without attenuating astro- and microgliosis. We also show that administration of ibuprofen through the drinking water results in a similar reduction in oxidative stress but with no observable effect on glial reactivity. The present study lends support to the notion that dietary anti-oxidants and non-steroidal anti-inflammatory drugs may be potential preventative agents against some of the pathological processes associated with neurodegenerative disease.

Topics: Acetylcysteine; Aldehydes; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Astrocytes; Cells, Cultured; Chronic Disease; Disease Models, Animal; Embryo, Mammalian; Fetal Tissue Transplantation; Free Radical Scavengers; Glial Fibrillary Acidic Protein; Gliosis; Ibuprofen; Lipid Peroxidation; Oxidative Stress; Protein Carbonylation; Rats; Time Factors

To evaluate whether chronic therapy with probiotics affects plasma levels of cytokines and oxidative/nitrosative stress parameters, as well as liver damage, in patients with various types of chronic liver disease.. A total of 22 nonalcoholic fatty liver disease (NAFLD) and 20 alcoholic liver cirrhosis (AC) patients were enrolled in the study and compared with 36 HCV-positive patients with chronic hepatitis without (20, CH) or with (16, CC) liver cirrhosis. All patients were treated with the probiotic VSL#3. Routine liver tests, plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6 and -10, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE), S-nitrosothiols (S-NO), were evaluated on days -30, 0, 90, and 120.. Treatment with VSL#3 exerted different effects in the various groups of patients: in NAFLD and AC groups, it significantly improved plasma levels of MDA and 4-HNE, whereas cytokines (TNF-alpha, IL-6, and IL-10) improved only in AC patients. No such effects were observed in HCV patients. Routine liver damage tests and plasma S-NO levels were improved at the end of treatment in all groups.. Results of the study suggest that manipulation of intestinal flora should be taken into consideration as possible adjunctive therapy in some types of chronic liver disease.

Topics: Adult; Aldehydes; Analysis of Variance; Chronic Disease; Cytokines; Fatty Liver; Female; Hepatitis C, Chronic; Humans; Liver Diseases, Alcoholic; Liver Function Tests; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Probiotics; S-Nitrosothiols; Statistics, Nonparametric

Chronic lymphoedema is one of the most frequent and debilitating complications after surgical and radiological tumour treatment. Prevention and therapy of lymphoedema is therefore an important problem of the rehabilitation of those patients.. To investigate whether chronic lymphoedema results in increased oxidative stress.. Prospective case-control study.. We obtained venous blood samples from patients (n=38) with chronic lymphoedema and determined biomarkers of prooxidative reactions and of antioxidative defense system in the erythrocytes or blood plasma: reduced and oxidized glutathione (GSH and GSSG), and lipid peroxidation products such as malondialdehyde (MDA) and 4-hydroxynonenal (HNE). Healthy volunteers (n=90) and patients who had undergone surgical and/or radiotherapeutic treatment of tumours without consequent lymphoedema (n=20) acted as controls.. The blood of patients with chronic lymphoedema contained lower concentrations of GSH and higher levels of GSSG and of MDA and HNE, compared with the control group. MDA was increased by about three-fold in the serum of the lymphoedema patients. Accelerated free radical formation and lipid peroxidation processes were further demonstrated by the liberation of MDA and HNE into the blood serum after manual lymph drainage.. Our data demonstrate enhanced formation of reactive oxygen species (ROS) and accelerated lipid peroxidation processes in chronic lymphoedematous tissue. The strengthening of antioxidative defense mechanisms could be useful in the therapy of chronic lymphoedema.

Topics: Aldehydes; Biomarkers; Case-Control Studies; Chronic Disease; Female; Free Radicals; Glutathione; Humans; Lipid Peroxidation; Lymphedema; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Prospective Studies; Reactive Oxygen Species

This study was designed to develop an animal model of alcoholic pancreatitis and to test the hypothesis that the dose of ethanol and the type of dietary fat affect free radical formation and pancreatic pathology. Female Wistar rats were fed liquid diets rich in corn oil (unsaturated fat), with or without a standard or high dose of ethanol, and medium-chain triglycerides (saturated fat) with a high dose of ethanol for 8 wk enterally. The dose of ethanol was increased as tolerance developed, which allowed approximately twice as much alcohol to be delivered in the high-dose group. Serum pancreatic enzymes and histology were normal after 4 wk of diets rich in unsaturated fat, with or without the standard dose of ethanol. In contrast, enzyme levels were elevated significantly by the high ethanol dose. Increases were blunted significantly by dietary saturated fat. Fibrosis and collagen alpha1(I) expression in the pancreas were not detectable after 4 wk of enteral ethanol feeding; however, they were enhanced significantly by the high dose after 8 wk. Furthermore, radical adducts detected by electron spin resonance were minimal with the standard dose; however, the high dose increased carbon-centered radical adducts as well as 4-hydroxynonenal, an index of lipid peroxidation, significantly. Radical adducts were also blunted by approximately 70% by dietary saturated fat. The animal model presented here is the first to demonstrate chronic alcohol-induced pancreatitis in a reproducible manner. The key factors responsible for pathology are the amount of ethanol administered and the type of dietary fat.

Topics: Aldehydes; Animals; Chronic Disease; Dietary Fats; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Fatty Acids; Female; Fibrosis; Free Radicals; Immunohistochemistry; Liver; Pancreas; Pancreatitis, Alcoholic; Proteins; Rats; Rats, Wistar

Lipid peroxidation is an autocatalytic mechanism leading to oxidative destruction of cellular membranes. The deleterious consequences of this mechanism are related in part to the formation of reactive aldehydic products that bind to intra- or extracellular molecules to form adducts. Specific antibodies directed against malondialdehyde (MDA) and 4-hydroxynonenal (HNE) adducts, major aldehydic metabolites of lipid peroxidation, allowed us to investigate in situ, with an immunohistochemical procedure, the occurrence of lipid peroxidation in a panel of different chronic liver diseases. Intracellular HNE and MDA adducts were detected respectively in 24 of 39 cases (62%) and in 12 of 34 cases investigated (35%). They were localized mainly in the cytoplasm of hepatocytes, with the strongest staining observed in hemochromatosis, Wilson's disease, and in areas of acute alcoholic hepatitis in cases of alcoholic liver diseases. A peculiar pattern of immunostaining was observed in primary biliary cirrhosis where biliary cells of destroyed but also intact bile ducts strongly expressed HNE adducts. The liver extracellular matrix also displayed MDA adducts (30 of 34 cases, 88%) and HNE adducts (23 of 39 cases, 59%). While HNE adducts were specifically localized on large bundles of collagen fibers, MDA adducts were detected in a thin reticular network and in sinusoidal cells around portal tracts or fibrous septa. In conclusion, lipid peroxidation by-products are detectable in chronic liver diseases. Immunohistochemical results suggest that this mechanism is implicated very early in the pathogenesis of some of these diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldehydes; Animals; Child; Child, Preschool; Chronic Disease; Cytoplasm; Extracellular Matrix; Female; Humans; Immunohistochemistry; Infant; Lipid Peroxidation; Liver; Liver Diseases; Male; Malondialdehyde; Middle Aged; Rats; Retrospective Studies

To assess the occurrence of lipid peroxidation in chronic hepatitis C and to evaluate its relation to pathological features and liver iron concentrations.. Liver biopsy samples of 43 patients with untreated chronic hepatitis C were studied by immunohistochemistry using specific antibodies directed against two major aldehyde metabolites of lipid peroxidation, malondialdehyde (MDA), and 4-hydroxynonenal (HNE).. MDA and HNE adducts (aldehydes covalently linked to another molecule) were detected in the liver samples in 77% and 30% of cases, respectively. MDA adducts were detected both in the extracellular matrix and sinusoidal cells localised in areas of periportal and lobular necrosis. HNE adducts appeared in the cytoplasm of only a few hepatocytes. Comparison of the semiquantitative assessment of adducts (MDA and HNE indexes) with the grading and the staging of chronic hepatitis showed that the MDA index was correlated with fibrosis score (p < 0.001) and the grade of activity (p < 0.01). There was also a tendency to correlation with liver iron concentration (p = 0.09). No correlation was observed between the HNE index and pathological features or liver iron concentration.. Lipid peroxidation products are detectable in the liver of chronic hepatitis C patients. The presence of MDA adducts in areas of active fibrogenesis and the correlation between the MDA index and fibrosis score suggest a role for lipid peroxidation in liver fibrosis.

Topics: Adult; Aged; Aldehydes; Chronic Disease; Female; Hepatitis C; Humans; Immunoenzyme Techniques; Iron; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Malondialdehyde; Middle Aged