Proatherogenic effects of 4-hydroxynonenal

Nègre‐Salvayre, Anne; Garoby-Salom, Sandra; Swiader, Audrey; Rouahi, Myriam; Pucelle, Mélanie; Salvayre, Robert

doi:10.1016/j.freeradbiomed.2016.12.038

Cited by 56 publications

(42 citation statements)

References 194 publications

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“…Both toxic and beneficial effects of 4‐HHE and 4‐HNE have been reported, with the outcome of the effect depending on their concentration. For example, on vascular cells, 4‐HNE can exert beneficial functions such as increased cell resistance to oxidative stress (range 0.1–1 µ m ), or toxic effects with higher concentrations such as the accumulation of HNE‐adducts along with inflammation and cell proliferation (range 1–10 µ m ) to cell dysfunctioning and apoptosis (>10–20 µ m ) . Bastide et al .…”

Section: Resultsmentioning

confidence: 99%

“…For example, on vascular cells, 4-HNE can exert beneficial functions such as increased cell resistance to oxidative stress (range 0.1-1 µm), or toxic effects with higher concentrations such as the accumulation of HNEadducts along with inflammation and cell proliferation (range 1-10 µm) to cell dysfunctioning and apoptosis (>10-20 µm). [22] Bastide et al [18] found a similar cytotoxic range for 4-HHE and 4-HNE, being more toxic to normal than apc-malignant cell lines, whereas MDA was not found to be cytotoxic in the range 2.5-80 µm. Whereas some rodent studies reported harmful effects of 4-HHE, such as inflammation, [20] adduct formation with insulin along with impairment of its hypoglycemic effects, [19] other studies attributed beneficial effects to 4-HHE, providing a possible mechanism through which n-3 PUFA have a cardioprotective effect.…”

Section: (Patho)physiological Consequences Of 4-hne and 4-hhe Formationmentioning

confidence: 96%

“…Pathophysiological effects have been described for both 4‐HHE and 4‐HNE . In strong contrast, more recent studies attributed some beneficial effects to low doses of 4‐HNE and 4‐HHE . Moreover, the beneficial effects of n‐3 PUFAs on cardiovascular health were even proposed to be mediated by the effects of 4‐HHE .…”

Section: Introductionmentioning

confidence: 99%

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Long‐Chain n‐3 PUFA Content and n‐6/n‐3 PUFA Ratio in Mammal, Poultry, and Fish Muscles Largely Explain Differential Protein and Lipid Oxidation Profiles Following In Vitro Gastrointestinal Digestion

Hecke

Goethals

Vossen

et al. 2019

Molecular Nutrition Food Res

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Scope Muscle food characteristics (fatty acid profile, heme‐Fe, intrinsic antioxidants) that relate to the formation of (patho)physiological oxidation products during gastrointestinal digestion are investigated. Methods and Results Muscles (n = 33) from 18 mammal, poultry, and fish species, of which some are mixed with lard to standardize their fatty acid profile, are digested in vitro. Lipid oxidation is assessed by thiobarbituric reactive substances (TBARS), n‐3 PUFA derivative 4‐hydroxy‐2‐hexenal and propanal, n‐6 PUFA derivative 4‐hydroxy‐2‐nonenal and hexanal, and protein oxidation by carbonylation. Digests of n‐3 PUFA‐rich fish demonstrated the highest n‐3 PUFA oxidation, whereas digests of various poultry and rabbit muscles showed highest n‐6 PUFA oxidation, which correlated significantly with the n‐6/n‐3 PUFA ratio. Without lard addition, lipid oxidation is significantly higher in chicken and pork loin digests versus beef and deer digests, whereas the opposite occurred when these muscles are mixed with lard. Protein carbonylation correlates significantly with levels of TBARS and the sum of hydroxy‐alkenals in digests. The n‐6/n‐3 PUFA ratio correlates well with the 4‐hydroxy‐2‐nonenal/4‐hydroxy‐2‐hexenal ratio in digests. Conclusions Muscular fatty acid profiles largely explain type and extent of lipid and protein oxidation during gastrointestinal digestion. Red meat only stimulates oxidation when digested with specific fat sources.

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Section: Resultsmentioning

confidence: 99%

Section: (Patho)physiological Consequences Of 4-hne and 4-hhe Formationmentioning

confidence: 96%

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Long‐Chain n‐3 PUFA Content and n‐6/n‐3 PUFA Ratio in Mammal, Poultry, and Fish Muscles Largely Explain Differential Protein and Lipid Oxidation Profiles Following In Vitro Gastrointestinal Digestion

Hecke

Goethals

Vossen

et al. 2019

Molecular Nutrition Food Res

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“…HNE adducts can accumulate progressively in the vascular system, leading to cellular dysfunctions and tissue damaging effects, which are involved in the progression of atherosclerosis. Moreover, HNE, by forming HNE-apoB adducts, contributes to the atherogenicity of oxidized low-density lipoproteins (LDL), leading to the formation of foam cells [ 14 ]. The presence of HNE-protein adducts has been detected in inflammation-related diseases, such as alcoholic liver disorders and chronic alcoholic pancreatitis, in which the increased formation of HNE-protein adducts was evidenced in acinar cells adjacent to the interlobular connective tissue [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders

et al. 2018

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Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age. Since the involvement and the role of lipid peroxidation-derived aldehydes, particularly of 4-hydroxynonenal (HNE), in neurodegenerations, inflammation, and cancer, has been discussed in several excellent recent reviews, in the present one we focus on the involvement of reactive aldehydes in other age-related disorders: osteopenia, sarcopenia, immunosenescence and myelodysplastic syndromes. In these aging-related disorders, characterized by increases of oxidative stress, both HNE and malondialdehyde (MDA) play important pathogenic roles. These aldehydes, and HNE in particular, can form adducts with circulating or cellular proteins of critical functional importance, such as the proteins involved in apoptosis in muscle cells, thus leading to their functional decay and acceleration of their molecular turnover and functionality. We suggest that a major fraction of the toxic effects observed in age-related disorders could depend on the formation of aldehyde-protein adducts. New redox proteomic approaches, pinpointing the modifications of distinct cell proteins by the aldehydes generated in the course of oxidative stress, should be extended to these age-associated disorders, to pave the way to targeted therapeutic strategies, aiming to alleviate the burden of morbidity and mortality associated with these disturbances.

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“…Atherosclerotic lesion is associated with the accumulation of reactive aldehydes derived from oxidized lipids. Accumulation of 4-HNE becomes an important risk factor that contributes to the atherogenicity of oxidized low-density lipoprotein (ox-LDL) and the development of atherosclerosis [75]. G. biloba leaf extract is reported to reduce ox-LDL and attenuate 4-HNE-induced production of matrix metalloproteinase-1 (MMP-1), probably through suppressing the activation of tyrosine-phosphorylated form of platelet-derived growth factor receptor beta in human coronary smooth muscle cells [76].…”

Section: Protection Against Cardiovascular Injurymentioning

confidence: 99%

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

Wang

et al. 2020

Biomolecules

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The toxic reactive aldehyde 4-hydroxynonenal (4-HNE) belongs to the advanced lipid peroxidation end products. Accumulation of 4-HNE and formation of 4-HNE adducts induced by redox imbalance participate in several cytotoxic processes, which contribute to the pathogenesis and progression of oxidative stress-related human disorders. Medicinal plants and bioactive natural compounds are suggested to be attractive sources of potential agents to mitigate oxidative stress, but little is known about the therapeutic potentials especially on combating 4-HNE-induced deleterious effects. Of note, some investigations clarify the attenuation of medicinal plants and bioactive compounds on 4-HNE-induced disturbances, but strong evidence is needed that these plants and compounds serve as potent agents in the prevention and treatment of disorders driven by 4-HNE. Therefore, this review highlights the pharmacological basis of these medicinal plants and bioactive compounds to combat 4-HNE-induced deleterious effects in oxidative stress-related disorders, such as neurotoxicity and neurological disorder, eye damage, cardiovascular injury, liver injury, and energy metabolism disorder. In addition, this review briefly discusses with special attention to the strategies for developing potential therapies by future applications of these medicinal plants and bioactive compounds, which will help biological and pharmacological scientists to explore the new vistas of medicinal plants in combating 4-HNE-induced deleterious effects.

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Proatherogenic effects of 4-hydroxynonenal

Cited by 56 publications

References 194 publications

Long‐Chain n‐3 PUFA Content and n‐6/n‐3 PUFA Ratio in Mammal, Poultry, and Fish Muscles Largely Explain Differential Protein and Lipid Oxidation Profiles Following In Vitro Gastrointestinal Digestion

Long‐Chain n‐3 PUFA Content and n‐6/n‐3 PUFA Ratio in Mammal, Poultry, and Fish Muscles Largely Explain Differential Protein and Lipid Oxidation Profiles Following In Vitro Gastrointestinal Digestion

Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders

Can Medicinal Plants and Bioactive Compounds Combat Lipid Peroxidation Product 4-HNE-Induced Deleterious Effects?

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