Lipid Peroxidation By-products Research Articles

Structural and Functional Changes in Human Insulin Induced by the Lipid Peroxidation Byproducts 4-Hydroxy-2-nonenal and 4-Hydroxy-2-hexenal

Lipid peroxidation produces many reactive byproducts including 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) derived from the peroxidation of n-3 and n-6 polyunsaturated fatty acids, respectively. HNE and HHE can modify circulating biomolecules through the formation of covalent adducts. It remains, however, unknown whether HHE and HNE could induce functional and structural changes in the insulin molecule, which may in turn be pivotal in the development of insulin resistance and diabetes. Recombinant human insulin was incubated in the presence of HHE or HNE, and the formation of covalent adducts on insulin was analyzed by mass spectrometry analysis. Insulin tolerance test in mice and stimulation of glucose uptake by 3T3 adipocytes and L6 muscle cells were used to evaluate the biological efficiency of adducted insulin compared with the native one. One to 5 adducts were formed on insulin through Michael adduction, involving histidine residues. Glucose uptake in 3T3-L1 and L6C5 cells as well as the hypoglycemic effect in mice was significantly reduced after treatment with adducted insulin compared to native insulin. The formation of HNE- and HHE-Michael adducts significantly disrupts the biological activity of insulin. These structural and functional abnormalities of the insulin molecule might contribute to the pathogenesis of insulin resistance.

Dietary d-limonene alleviates insulin resistance and oxidative stress–induced liver injury in high-fat diet and L-NAME-treated rats

Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of chronic liver disease worldwide. The pathogenesis of metabolic syndrome associated with NAFLD is still under debate. AIM OF THE SCOPE: This study has investigated the hepatic biochemical and histological changes and also insulin resistance in metabolic syndrome associated with NAFLD. Young male Wistar rats fed a high-fat diet (HFD 42.2% beef tallow) together with N ( ω )-nitro-L-arginine methyl ester (L-NAME; 80 mg/L in drinking water) for 8 weeks and subsequently with 2% d-limonene for the final 4 weeks. HFD-fed rats treated with L-NAME showed increased systolic blood pressure, heart rate, fasting blood glucose, plasma insulin, hepatic marker enzymes, hepatic lipids, circulatory lipid peroxidation by-products, and hepatic phase I enzyme activities with decreased circulatory nonenzymic antioxidant concentrations and hepatic phase II enzyme activities. Dietary supplementation with d-limonene reversed the HFD and L-NAME-induced changes and restored pathological alteration of liver and pancreas. These data provide new insights into the therapeutic approach of d-limonene against the development of the metabolic syndrome associated with NAFLD.

Thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole derivatives of isonicotinic acid hydrazide: Synthesis and their biological evaluation

A series of thiazolidin-4-one (2a-h, 3a-h), azetidin-2-one (4a- h) and 1,3,4-oxadiazole (5a-h) derivatives of isoninicotinic acid hydrazide (INH) were synthesized in order to obtain new compounds with potential anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities. The structures of the new compounds were supported by their IR, 1H-NMR and mass spectral data. All compounds were evaluated for their anti-inflammatory activity by the carrageenan-induced rat paw edema test method. Eleven of the new compounds, out of 32, showed very good anti-inflammatory activity in the carrageenan-induced rat paw edema test, with significant analgesic activity in the tail immersion method together with negligible ulcerogenic action. The compounds, which showed less ulcerogenic action, also showed reduced malondialdehyde content (MDA), which is one of the by-products of lipid peroxidation. The study showed that the compounds inhibited the induction of gastric mucosal lesions and it can be suggested from the results that their protective effects may be related to inhibition of lipid peroxidation in the gastric mucosa.

Anti-acrolein treatment improves behavioral outcome and alleviates myelin damage in experimental autoimmune enchephalomyelitis mouse

Oxidative stress is considered a major contributor in the pathology of multiple sclerosis (MS). Acrolein, a highly reactive aldehyde byproduct of lipid peroxidation, is thought to perpetuate oxidative stress. In this study, we aimed to determine the role of acrolein in an animal model of MS, experimental autoimmune enchephalomyelitis (EAE) mice. We have demonstrated a significant elevation of acrolein protein adduct levels in EAE mouse spinal cord. Hydralazine, a known acrolein scavenger, significantly improved behavioral outcomes and lessened myelin damage in spinal cord. We postulate that acrolein is an important pathological factor and likely a novel therapeutic target in MS.

Anti-clastogenic potential of carnosic acid against 7,12-dimethylbenz(a) anthracene (DMBA)-induced clastogenesis

Carnosic acid, a primary phenolic compound found in the leaves of rosemary (Rosmarinus officinalis), has diverse pharmacological and biological activities. The aim of the present study was to investigate the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. The frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations (cytogenetic end points), the status of Phase I and II detoxification enzymes, lipid peroxidation by-products and antioxidants (biochemical endpoints) were analyzed to assess the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. Oral pretreatment of carnosic acid for five days to DMBA-treated hamsters significantly protected DMBA-induced clastogenesis as well as biochemical abnormalities. Although the exact mechanism of anti-clastogenic effects of carnosic acid is unclear, the antioxidant potential and effect on modulation of Phase I and II detoxification enzymes could play a possible role.

SK-PC-B70M alleviates neurologic symptoms in G93A-SOD1 amyotrophic lateral sclerosis mice

SK-PC-B70M, an oleanolic-glycoside saponins fraction extracted from the root of Pulsatilla koreana, carries active ingredient(s) that protects the cytotoxicity induced by Aβ(1–42) in SK-N-SH cells. It was recently demonstrated that SK-PC-B70M improved scopolamine-induced deficits of memory consolidation and spatial working memory in rats, and reduced Aβ levels and plaque deposition in the brains of the Tg2576 mouse model of Alzheimer disease. In the present study, we investigated whether SK-PC-B70M produces helpful effects on the pathology of the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis (ALS). Administration of SK-PC-B70M (100 or 400 mg/kg/day) from 8 weeks to 16 weeks of age attenuated neurological deficits of G93A-SOD1 mice in several motor-function-related behavioral tests. SK-PC-B70M treatment significantly suppressed the accumulation of the by-products of lipid peroxidation, malonedialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), in the spinal cord of G93A-SOD1 mice. Moreover, histologic analysis stained with cresyl violet or anti-choline acetyltransferase (ChAT) revealed that SK-PC-B70M suppressed neuronal loss in the ventral horn of the spinal cords of G93A-SOD1 mice. These results suggest that SK-PC-B70M affords a beneficial effect on neurologic deficits of G93A-SOD1 ALS mice.

Cyanidin-3-O-glucoside Protection against TNF-α-Induced Endothelial Dysfunction: Involvement of Nuclear Factor-κB Signaling

Oxidative stress and inflammation are considered to play a pivotal role in vascular endothelial dysfunction by triggering activation of transcription factors, such as NF-κB, functionally dependent on cellular redox status. The anthocyanin cyanidin-3-O-glucoside (C3G), as well as other phytochemicals recognized as potent antioxidants and free radical scavengers, may act as modulators of gene regulation and signal transduction pathways. This study demonstrates that C3G is able to protect human endothelial cells against alterations induced by TNF-α, including the activation of NF-κB, increased gene expression of adhesion molecules, leukocyte adhesion to endothelium, and intracellular accumulation of H2O2 and lipid peroxidation byproducts. These observations contribute to provide a conceptual background for the understanding of the mechanisms underlying the role of C3G, as well as other dietary plant polyphenols, in the prevention of diseases associated with inflammation and oxidative stress, including atherosclerosis.

The cytotoxic mechanism of malondialdehyde and protective effect of carnosine via protein cross-linking/mitochondrial dysfunction/reactive oxygen species/MAPK pathway in neurons

The accumulation of malondialdehyde (MDA), a lipid peroxidation by-product that has been used as an indicator of cellular oxidation status, is significantly increased in many neurological diseases such as brain ischemia/reperfusion, Alzheimer's disease and Parkinson's disease in vivo. In the present study, we found that MDA treatment in vitro reduced cortical neuronal viability in a time- and dose-dependent manner and induced cellular apoptosis as well as necrosis simultaneously. Furthermore, exposure to MDA led to accumulation of intracellular reactive oxygen species, dysfunction of mitochondria (denoted by the loss of mitochondrial transmembrane potential (Δ ψm)) and activation of JNK and ERK. Carnosine exhibited better protection against MDA-induced cell injury than antioxidant N-acetyl-cysteine (NAC) with its multi-potency, which alleviated MDA-induced protein cross-linking, Δ ψm decrease, reactive oxygen species burst, JNK and ERK activation. In conclusion, our results suggest that MDA induced cell injury in vitro via protein cross-linking and successive mitochondrial dysfunction, and the activation of reactive oxygen species-dependent MAPK signaling pathway. Carnosine alleviated all these alterations induced by MDA, but NAC merely inhibited Bcl-2 family-related activation of JNK and ERK. These results prompt the possibility that carnosine, but not other conventional antioxidants, can protect neurons against MDA-induced injury through decomposition of protein cross-linking toxicity and may serve as a novel agent in the treatment of neurodegenerative diseases.

Dietary antioxidants, lipid peroxidation and plumage colouration in nestling blue tits Cyanistes caeruleus

Carotenoid pigments are responsible for many of the red, yellow and orange plumage and integument traits seen in birds. One idea suggests that since carotenoids can act as antioxidants, carotenoid-mediated colouration may reveal an individual's ability to resist oxidative damage. In fact, there is currently very little information on the effects of most dietary-acquired antioxidants on oxidative stress in wild birds. Here, we assessed the impacts on oxidative damage, plasma antioxidants, growth and plumage colouration after supplementing nestling blue tits Cyanistes caeruleus with one of three diets; control, carotenoid treatment or α-tocopherol treatment. Oxidative damage was assessed by HPLC analysis of plasma levels of malondialdehyde (MDA), a by-product of lipid peroxidation. Contrary to predictions, we found no differences in oxidative damage, plumage colouration or growth rate between treatment groups. Although plasma lutein concentrations were significantly raised in carotenoid-fed chicks, α-tocopherol treatment had no effect on concentrations of plasma α-tocopherol compared with controls. Interestingly, we found that faster growing chicks had higher levels of oxidative damage than slower growing birds, independent of treatment, body mass and condition at fledging. Moreover, the chromatic signal of the chest plumage of birds was positively correlated with levels of MDA but not plasma antioxidant concentrations: more colourful nestlings had higher oxidative damage than less colourful individuals. Thus, increased carotenoid-mediated plumage does not reveal resistance to oxidative damage for nestling blue tits, but may indicate costs paid, in terms of oxidative damage. Our results indicate that the trade-offs between competing physiological systems for dietary antioxidants are likely to be complex in rapidly developing birds. Moreover, interpreting the biological relevance of different biomarkers of antioxidant status represents a challenge for evolutionary ecology.

Molecular Regulations Induced by Acrolein in Neuroblastoma SK-N-SH Cells: Relevance to Alzheimer's Disease

Acrolein is the most reactive aldehyde among the by-products of lipid peroxidation. Growing evidence indicates that acrolein may play an important role in the pathogenesis of Alzheimer's disease (AD). In AD, levels of acrolein are significantly higher in hippocampus and temporal cortex regions of the brain. However, little is known about its toxicity in neuronal cells. Using the neuroblastoma cell line SK-N-SH, our results show that acrolein is toxic from 10 μM, but its toxicity does not induce the activation of caspase-3 and DNA fragmentation. Protein carbonylation and 4-hydroxynonenal levels were increased after 0.5 hr and 1 hr of treatment, respectively. Furthermore acrolein induced a biphasic effect on glutathione levels with a rapid depletion followed by a progressive increase. We have further investigated the regulation of different redox signaling pathways. A treatment with 10 μM of acrolein for 30 min activated NFκB while this activation was suppressed after a 24 hrs of treatment. In contrast, Nrf2 was activated only after 24 hrs of acrolein exposure. Consequently, the expression of heme oxygenase-1 and γ-glutamyl-cysteine-synthase were elevated after 24 hrs of acrolein treatment. Sirt-1 was also upregulated after 24 hrs of acrolein treatment. The p66Shc and ERK1/2 proteins are known to be involved in oxidative stress. Acrolein, at 10 μM, induced the phosphorylation of p66Shc and ERK1/2 only after a short period of treatment. Collectively, these data strengthen the contribution of acrolein in the induction of oxidative stress as observed in mild cognitive impairment and in AD brain.

Modulation of Hydrogen Peroxide and Acrolein-Induced Oxidative Stress, Mitochondrial Dysfunctions and Redox Regulated Pathways by the Bacopa Monniera Extract: Potential Implication in Alzheimer's Disease

Acrolein is one of the by-products of lipid peroxidation. Due to its high reactivity, it is not only a marker of lipid peroxidation but could also be an initiator of oxidative stress by adducting cellular nucleophilic groups. In brains of Alzheimer's disease (AD) patients, levels of acrolein are significantly higher in vulnerable brain region and, on primary hippocampal culture, it is more toxic than 4-hydroxyl-nonenal. The toxicity of the amyloid-beta peptide is mediated through the generation of hydrogen peroxide (H2O2). The actions of H2O2 include oxidative modifications of proteins, lipids, and DNA as observed in AD. Bacopa monniera (BM) has a long history of use in India as a memory-enhancing therapy. The objective of our study was to investigate the neuroprotective effects of the standardized extracts of BM against acrolein and H2O2 and to elucidate the mechanisms underlying this protection. Our results show that a pre-treatment with the BM extract protected the human neuroblastoma cell line SK-N-SH against H2O2 and acrolein. We demonstrated that BM pre-treatment significantly inhibited the generation of intracellular reactive oxygen species in addition to preserving the mitochondrial membrane potential. BM pre-treatment also prevented the modifications of the activity of several redox regulated proteins, i.e., NF-kappaB, Sirt1, ERK1/2, and p66Shc, so as to favor cell survival in response to oxidative stress. Thus, our findings demonstrate that BM can protect human neuroblastoma cells against H2O2 and acrolein through different mechanisms involved in the pathophysiology of AD and could have a therapeutic application in the prevention of AD.

Lipid Peroxidation-Derived Reactive Aldehydes Directly and Differentially Impair Spinal Cord and Brain Mitochondrial Function

Mitochondrial bioenergetic dysfunction in traumatic spinal cord and brain injury is associated with post-traumatic free radical-mediated oxidative damage to proteins and lipids. Lipid peroxidation by-products, such as 4-hydroxy-2-nonenal and acrolein, can form adducts with proteins and exacerbate the effects of direct free radical-induced protein oxidation. The aim of the present investigation was to determine and compare the direct contribution of 4-hydroxy-2-nonenal and acrolein to spinal cord and brain mitochondrial dysfunction. Ficoll gradient-isolated mitochondria from normal rat spinal cords and brains were treated with carefully selected doses of 4-hydroxy-2-nonenal or acrolein, followed by measurement of complex I- and complex II-driven respiratory rates. Both compounds were potent inhibitors of mitochondrial respiration in a dose-dependent manner. 4-Hydroxy-2-nonenal significantly compromised spinal cord mitochondrial respiration at a 0.1-muM concentration, whereas 10-fold greater concentrations produced a similar effect in brain. Acrolein was more potent than 4-hydroxy-2-nonenal, significantly decreasing spinal cord and brain mitochondrial respiration at 0.01 muM and 0.1 muM concentrations, respectively. The results of this study show that 4-hydroxy-2-nonenal and acrolein can directly and differentially impair spinal cord and brain mitochondrial function, and that the targets for the toxic effects of aldehydes appear to include pyruvate dehydrogenase and complex I-associated proteins. Furthermore, they suggest that protein modification by these lipid peroxidation products may directly contribute to post-traumatic mitochondrial damage, with spinal cord mitochondria showing a greater sensitivity than those in brain.

Protective potential of trans-resveratrol against 4-hydroxynonenal induced damage in PC12 cells

The role of 4-hydroxynonenal (4-HNE), a byproduct of membrane lipid peroxidation has been suggested in neurodegeneration. However, the underlying mechanisms are poorly understood. The investigations were carried out to study the preventive potential of trans-resveratrol against 4-HNE induced damage in PC12 cells. Trans-resveratrol, a natural compound obtained from grape skin and found in red wine, is reported to have wide pharmacological window. Cells pretreated with trans-resveratrol (5, 10 and 25 μM) for 24 h were exposed to 4-HNE (25 μM) for 2 h. Pre-treatment of trans-resveratrol was found to be significantly effective in countering the cytotoxic responses of 4-HNE. Significant reduction in reactive oxygen species generation, restoration of intracellular glutathione, and lipid peroxidation levels suggest the improved antioxidant defense system in the cells pretreated with trans-resveratrol. Further, 4-HNE induced alterations in the protein expression of mitochondria-mediated apoptosis markers (Bax, Bcl-2 and Caspase-3) were significantly restored by pre-treatment of trans-resveratrol suggesting the protective potential of trans-resveratrol in PC12 cells against 4-HNE induced oxidative damage. Together these data show the prophylactic potential of trans-resveratrol in oxidative stress mediated apoptotic neurodegeneration.

Serum oxidative stress is increased in patients with post cholecystectomy bile duct injury

Post-cholecystectomy bile duct injuries are identified by the onset of jaundice as well as elevated bilirubin and alkaline phosphatase levels during the peri-operative period. It is unknown how serum oxidative stress markers are modified in patients with post-cholecystectomy bile duct injuries. To determine serum oxidative stress marker levels (lipid peroxidation by-products, nitrites/nitrates and total antioxidant capacity) in patients with post-cholecystectomy bile duct injuries. A prospective, transversal and analytical study was designed with two groups. Group 1: 5 healthy volunteer subjects. Group 2: 52 patients with post-cholecystectomy bile duct injuries (43 female and 9 male). An elective bilio-digestive reconstruction was performed at week 8. The serum oxidative stress marker levels were quantified by colorimetric method. Patients with bile duct injuries had a significant increased serum lipid peroxides (malondialdehyde and 4-hydroxy-alkenals) and nitric oxide metabolites (nitrites/nitrates) levels compared to the control group. In contrast, total antioxidant capacity in patients with bile duct injuries remained similar compared to healthy controls. The results show that oxidative stress is usually associated to bile duct injury.

Potential Role of Acrolein in Neurodegeneration and in Alzheimers Disease

Lipid peroxidation leads to the formation of a number of aldehydes by-products, including acrolein. The most abundant aldehydes are 4-hydroxy-nonenal (4-HNE) and malondialdehyde (MDA) while acrolein is the most reactive. In Alzheimer's brain, acrolein was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In late onset Alzheimer's disease (AD), a 2-fold increase in levels of acrolein/guanosine adducts in nDNA were isolated from the hippocampus of AD as compared to age-matched control. These adducts are biologically relevant in that they may promote DNA-DNA and DNA-protein cross-linking while 4-HNE/guanosine adduct in nDNA was not elevated in AD. In AD, the activity of the glutathione-S-transferase, the main enzyme responsible for the detoxification of acrolein is significantly decreased in hippocampus. On neuronal primary culture from hippocampus, acrolein caused cell death and its toxicity is higher than 4-hydroxynonenal. Acrolein could modulate tau phosphorylation through different pathways. Acrolein has been shown to inhibit the mitochondrial activity. Due to its high reactivity, acrolein is not only a marker of lipid peroxidation but also an initiator of oxidative stress by adducting cellular nucleophilic groups found on proteins, lipids, and nucleic acid. As a strong electrophile molecule, acrolein can react about 110-150 times faster with the thiol group of cysteine than with 4-hydroxynonenal and decrease the level of the antioxidant glutathione. Taken together, these reactions suggest that acrolein could play a role in the pathophysiology of AD. In this review, we will summarize some mechanisms implicated in the toxicity of this by-product of lipid peroxidation in brain and their implication in AD.

Reactive γ-ketoaldehydes formed via the isoprostane pathway disrupt mitochondrial respiration and calcium homeostasis

Isoketals (IsoKs) are γ-ketoaldehydes formed via the isoprostane pathway of arachidonic acid peroxidation and are among the most reactive by-products of lipid peroxidation. IsoKs selectively adduct to protein lysine residues and are highly cytotoxic, but the targets and molecular events involved in IsoK-induced cell death are poorly defined. Our previous work established that physiologically relevant aldehydes induce mitochondrial dysfunction (Kristal et al., J. Biol. Chem. 271:6033–6038; 1996). We therefore examined whether IsoKs induced mitochondrial dysfunction. Incubation of mitochondria with synthetic IsoKs in the presence or absence of Ca 2+ was associated with alterations in mitochondrial respiration, membrane potential (ΔΨ), and pyridine nucleotide redox state. IsoKs dose dependently (0.5–4 µM) accelerated liver mitochondria swelling induced by low concentrations of Ca 2+ and Zn 2+ or by the prooxidant tert-butylhydroperoxide , and release of cytochrome c, with similar observations in heart/brain mitochondria. The mitochondrial permeability transition (mPT) inhibitor cyclosporine A delayed IsoK-induced mitochondria dysfunction. The actions of IsoKs are consistent with interactions with cytochrome c, a protein rich in lysine residues. Direct reaction of IsoKs with select lysines in cytochrome c was demonstrated using high-resolution mass spectrometry. Overall, these results suggest that IsoKs may, in part, mediate their cytotoxic effects through induction of the mPT and subsequent activation of downstream cell death cascades.

Deficiency of ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) leads to vulnerability to lipid peroxidation

Lipid peroxidation has many deleterious effects on cells, and in the nervous system is considered to be involved in the pathogenesis of neurodegenerative diseases. To suppress lipid peroxidation, cells have various defense systems such as glutathione and thioredoxin, and defects in these defense systems will result in disturbance of normal cellular functions. Here we report that deficiency of ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) leads to vulnerability to lipid peroxidation both in vivo and in vitro, through analyses of the UCH-L1-deficient mutant mouse gracile axonal dystrophy ( gad). In the gracile fasciculus of gad mice, punctate deposits were observed to be immunoreactive for 4-hydroxy-2-nonenal, a by-product of lipid peroxidation. The motor deficits of gad mice were worsened by a diet deficient in vitamin E. When neurons from dorsal root ganglions (DRG) were cultured in the vitamin E-free medium, cell death was increased in the neurons of gad mice. These data suggest that UCH-L1 has a function in protecting DRG neurons from lipid peroxidation. Further, we describe newly identified properties: that UCH-L1 is localized on the inside of the plasma membrane of DRG neurons, and that UCH-L1 binds to phosphatidic acid according to the redox status and presence of mono-ubiquitin protein. These findings will provide clues for elucidating the physiological function of UCH-L1.

Induction of oxidative stress and apoptosis by silver nanoparticles in the liver of adult zebrafish

Silver nanoparticles (AgNPs) may induce deleterious effects in aquatic life on environmental release. The hepatotoxicity of AgNPs was assessed in the liver of adult zebrafish, with the aim of studying the roles of oxidative damage and apoptosis. Zebrafish were exposed to an AgNP solution in which free Ag + ions were absent at the time of treatment. However, the metal-sensitive metallothionein 2 (MT2) mRNA was induced in the liver tissues of AgNP-treated zebrafish, suggesting that Ag + ions were released from AgNPs after treatment. It is also possible that MT2 mRNA was induced in the liver tissues by AgNP-generated free radicals. A number of cellular alterations including disruption of hepatic cell cords and apoptotic changes were observed in histological analysis of the liver tissues. The levels of malondialdehyde, a byproduct of cellular lipid peroxidation, and total glutathione were increased in the tissues after treatment with AgNPs. The mRNA levels of the oxyradical-scavenging enzymes catalase and glutathione peroxidase 1a were reduced in the tissues. AgNP treatment induced DNA damage, as demonstrated by analysis with the double-strand break marker γ-H2AX and the expression of p53 protein in liver tissues. In addition, the p53-related pro-apoptotic genes Bax, Noxa, and p21 were upregulated after treatment with AgNPs. These data suggest that oxidative stress and apoptosis are associated with AgNP toxicity in the liver of adult zebrafish.

Lipid Peroxidation in Acute Respiratory Distress Syndrome and Liver Failure

Lipid peroxidation processes (LPO) are evident in many organ failures. Due to their toxic properties, they are causative for cellular dysfunction at the site of their origin and far beyond. This study was conducted to investigate differences in LPO pattern of patients with established acute respiratory distress syndrome (ARDS) and patients with end-stage liver failure undergoing liver transplantation (LTX) as two mayor prototypes of organ failure. In this prospective, nonrandomized, controlled trial, we examined LPO by measuring malondialdehyde (MDA), and the volatile aldehydes hexanal and propanal as LPO-markers. Eighteen patients with ARDS, 16 subjects undergoing liver transplantation due to liver failure, and 8 healthy controls were included to the study. ARDS patients showed significantly higher levels in MDA concentrations than LTX and controls, respectively. However, MDA levels of patients with end-stage liver failure were equal to those of controls. Blood concentrations of hexanal and propanal, specific by-products of lipid peroxidation, were elevated in both patient groups, but significantly higher only in LTX. Unexpectedly, hexanal and propanal concentrations were significantly higher in LTX than in ARDS patients. In both patient groups, MDA showed no differences between arterial and mixed venous blood, whereas volatile aldehydes were higher in arterial than in mixed venous compartment. Both ARDS and LTX-patients showed significant evidence of enhanced LPO. However, proportions of MDA and volatile aldehydes differed substantially between the groups. Thus, for the interpretation of LPO markers, disease-specific factors have to be taken into account. Distinctions might be attributable to differences in the effected lipid components or variations in metabolism.

The effects of polyphenol-containing antioxidants on oxidative stress and lipid peroxidation in Type 2 diabetes mellitus without complications

The hyperglycemia-induced oxidative stress in diabetes mellitus (DM) is the major factor in the pathogenesis of cardiovascular complications. The phenolic compounds are potent antioxidants that can reverse the factors leading to cardiovascular complications in DM. The aim of this study was to determine the antagonizing effects of a polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid, on oxidative stress in Type 2 diabetic patients. A total of 114 male and female non-smokers (56 study, 58 placebo) with Type 2 DM and without any complications were recruited. The blood levels of fasting blood glucose, glycated hemoglobin, LDL, HDL, triglycerides, plasma malondialdehyde (MDA), total glutathione (GSH), hydrogen peroxide, and antioxidant capacity (AOC) were determined at the beginning and at the end of the 3-month trial. The differences of the data changes between the groups were statistically analyzed by Mann-Whitney U test. The study group showed a decrease in LDL and an increase in HDL and the comparison with the difference in placebo group was statistically significant (p<0.001 for LDL and p<0.001 for HDL). Accordingly, as a by-product of lipid peroxidation, plasma MDA was decreased in the study group compared to the placebo group (p<0.001). As an indicator of increased antioxidant defense, total plasma GSH and AOC increased more in the study group compared to control group (p<0.001). These observations indicated that the polyphenol-rich antioxidant supplement containing pomegranate extract, green tea extract, and ascorbic acid has important antagonizing effects on oxidative stress and lipid peroxidation in patients with Type 2 DM and might be beneficial in preventing cardiovascular complications.