The Important Role of Lipid Peroxidation Processes in Aging and Age Dependent Diseases

Spiteller, Gerhard

doi:10.1007/s12033-007-0057-6

Cited by 73 publications

(53 citation statements)

References 43 publications

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“…Increased lipid peroxidation has been associated with the development and progression of a number of chronic human diseases including CVD and diabetes (98)(99)(100)(101) . It damages biological membranes changing membrane fluidity and functions including receptor activity, and nutrient and ion transport.…”

Section: Effect Of N-3 Pufa On Lipid Peroxidationmentioning

confidence: 99%

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

Kelley

Adkins

2012

Proc. Nutr. Soc.

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We have reviewed effects of long chain (LC) n-3 PUFA on markers of atherosclerosis in human subjects with a focus on individual effects of EPA and DHA. Initial results from epidemiological studies suggested that LC n-3 PUFA from fish oils (FO) reduced incidence of CVD; those results have been confirmed in interventional studies. Dietary intervention with n-3 PUFA decreased fasting and postprandial TAG, number of remnant-like chylomicron particles, large VLDL, and total and small dense LDL particles. It increased mean size of LDL particles by increasing number of large and decreasing those of small dense particles. With some exceptions, n-3 PUFA decreased blood pressure (BP) and heart rate (HR), flow-mediated dilation (FMD) and plasma concentrations of inflammatory markers. n-3 PUFA also decreased circulating adhesion molecules and intima-media thickness (IMT) in some but not other studies. For IMT, results varied with the sex and artery being examined. EPA effects on FMD are endothelial cell dependent, while those of DHA seem to be endothelial cell independent. Individually, both EPA and DHA decreased TAG and inflammatory markers, but only DHA decreased HR, BP and number of small dense LDL particles. Results varied because of dose and duration of n-3 PUFA, EPA:DHA, health status of subjects and other reasons. Future studies are needed to determine optimal doses of EPA and DHA individually, their synergistic, additive or antagonistic effects, and to understand underlying mechanisms. In conclusion, n-3 PUFA decreased several risk factors for atherosclerosis without any serious adverse effects. TAG: LDL size and numbers: Intima-media thickness: Blood pressureAtherosclerosis comes from the Greek words athero (meaning gruel or paste) and sclerosis (hardness). It is a common disorder of the arteries in which fat and other substances build up in and on the walls of arteries and form hard structures called plaques (1) . The plaques can make the artery narrow and less flexible, making it harder for blood to flow. If the coronary arteries become narrow, blood flow to the heart can slow down or stop. This can cause chest pain (stable angina), shortness of breath, heart attack and other symptoms. Pieces of plaque can break off and move through the bloodstream (embolisation). This is a common cause of heart attack and stroke. Blood clots can also form around a tear (fissure) in the plaque and block blood flow. If the clot moves into an artery in the heart, lungs or brain, it can cause a stroke, heart attack or pulmonary embolism (2) . Eighty million American adults (approximately one in three) have CVD (3) . CVD is the number one cause of deaths in the US accounting for 34 % of all deaths or 2400 deaths each day. It is a major public health problem with an annual economic loss of $400 billion (3) .

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Section: Effect Of N-3 Pufa On Lipid Peroxidationmentioning

confidence: 99%

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

Kelley

Adkins

2012

Proc. Nutr. Soc.

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“…GSH also has an indispensable role in the AO defense. GSH redox cycle is a crucial protective mechanism against cell membrane damage by lipid peroxidation (LPO), a chain reaction in which polyunsaturated fatty acids (PUFA) in membrane lipids are being oxidized by ROS (Spiteller 2007, Liu et al 2005. The antioxidant enzyme GPx uses GSH for reducing LOOH and hydrogen peroxide (H 2 O 2 ), while GR reduces GSSG with a simultaneous oxidation of nicotinamide adenine dinucleotide phosphate (NADPH).…”

Section: Introductionmentioning

confidence: 99%

Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

Stojiljković

Pejić

Kasapović

et al. 2012

An. Acad. Bras. Ciênc.

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The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro-and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSHrelated antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.

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“…Rats were exposed to CCl 4 , an established model of in vivo oxidative stress (26). MA conjugates of HNE and ONE metabolites were detected in the urine by LC-MS/MS comparison with synthetic standards.…”

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confidence: 99%

Mercapturic Acid Conjugates of 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal Metabolites Are in Vivo Markers of Oxidative Stress

Kuiper

Miranda

Sowell

et al. 2008

Journal of Biological Chemistry

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Oxidative stress-induced lipid peroxidation leads to the formation of cytotoxic and genotoxic 2-alkenals, such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE). Lipid-derived reactive aldehydes are subject to phase-2 metabolism and are predominantly found as mercapturic acid (MA) conjugates in urine. This study shows evidence for the in vivo formation of ONE and its phase-1 metabolites, 4-oxo-2-nonen-1-ol (ONO) and 4-oxo-2-nonenoic acid (ONA). We have detected the MA conjugates of HNE, 1,4-dihydroxy-2-nonene (DHN), 4-hydroxy-2-nonenoic acid (HNA), the lactone of HNA, ONE, ONO, and ONA in rat urine by liquid chromatography-tandem mass spectrometry comparison with synthetic standards prepared in our laboratory. CCl 4 treatment of rats, a widely accepted animal model of acute oxidative stress, resulted in a significant increase in the urinary levels of DHN-MA, HNA-MA lactone, ONE-MA, and ONA-MA. Our data suggest that conjugates of HNE and ONE metabolites have value as markers of in vivo oxidative stress and lipid peroxidation. Lipid peroxidation (LPO)2 products are breakdown products of fatty acids formed under conditions of oxidative stress. 4-Hydroxy-2-nonenal (HNE) is a well established LPO product that has been shown to contribute to the development and progression of age-related diseases such as Alzheimer and atherosclerosis (1-4) in addition to being cytotoxic and genotoxic (5, 6). The mechanism of formation for HNE from linoleic acid via 4-hydroperoxy-2-nonenal (HPNE) has been previously demonstrated (7). Once HNE is formed, it can be further metabolized by cytochrome P450, aldehyde dehydrogenase, aldo-keto reductase (AKR), and conjugated by glutathione S-transferase (GST). Certain isoforms of murine and human P450s (8) and aldehyde dehydrogenase (9) can catalyze the oxidation of HNE to 4-hydroxy-2-nonenoic acid (HNA). When conjugated, HNA can undergo spontaneous intramolecular condensation, resulting in lactone formation (10). Aldo-keto reductase 1B1 has been shown to reduce HNE to form 1,4-dihydroxy-2-nonene (DHN) (11). Glutathione (GSH) can form conjugates with HNE and other LPO products (6) via a Michael-type addition mediated by . The GSH can then be further metabolized in the liver and in the kidney to form mercapturic acid (MA), resulting in the conjugates shown in Fig. 1. A number of studies have examined HNE and its metabolites in vivo (10,(15)(16)(17)(18) and have demonstrated the formation of the MA conjugates HNE-MA, DHN-MA, HNA-MA, and HNA-MA lactone in vivo (10). In addition, histidine-1,4-dihydroxynonane (His-DHN) and His-HNA have been found in the urine of obese Zucker rats, a model of metabolic syndrome (19).Not only can HPNE break down into HNE, but it can also form 4-oxo-2-nonenal (ONE) as shown in vitro (20) and in cultured cells (21). ONE can be reduced at the C-4 position by carbonyl reductase to form HNE (22), but it can also be reduced at the C-1 position by aldo-keto reductase to form 4-oxo-2-nonen-1-ol (ONO) (21,23,24) or oxidized by aldehyde dehydrogenase (human aldehyde dehy...

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The Important Role of Lipid Peroxidation Processes in Aging and Age Dependent Diseases

Cited by 73 publications

References 43 publications

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

Similarities and differences between the effects of EPA and DHA on markers of atherosclerosis in human subjects

Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

Mercapturic Acid Conjugates of 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal Metabolites Are in Vivo Markers of Oxidative Stress

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