{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T04:12:19Z","timestamp":1793419939302,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Lipid aldehydes originating from the peroxidation of n-3 and n-6 polyunsaturated fatty acids are increased in hemodialysis (HD) patients, a process already known to promote oxidative stress. However, data are lacking for patients with chronic kidney disease (CKD) before the initiation of HD. We prospectively evaluated the changes of plasma concentrations of two major lipid aldehydes, 4-HHE and 4-HNE, according to the decrease of glomerular filtration rate (GFR) in 40 CKD and 13 non-CKD participants. GFR was measured by inulin or iohexol clearance. Thus, 4-hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) were quantitated in plasma by gas chromatography coupled with mass spectrometry and their covalent adducts on proteins were quantified by immunoblotting. On the one hand, 4-HHE plasma concentration increased from CKD stage I\u2013II to CKD stage IV\u2013V compared to non-CKD patients (4.5-fold higher in CKD IV\u2013V, p &lt; 0.005). On the other hand, 4-HNE concentration only increased in CKD stage IV\u2013V patients (6.2-fold, p &lt; 0.005). The amount of covalent adducts of 4-HHE on plasma protein was 9.5-fold higher in CKD patients than in controls (p &lt; 0.005), while no difference was observed for 4-HNE protein adducts. Plasma concentrations of 4-HNE and 4-HHE are increased in CKD IV\u2013V patients before the initiation of hemodialysis.<\/jats:p>","DOI":"10.3390\/toxins12090567","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T11:22:43Z","timestamp":1599132163000},"page":"567","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Two Toxic Lipid Aldehydes, 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), Accumulate in Patients with Chronic Kidney Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Christophe O.","family":"Soulage","sequence":"first","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.","family":"Pelletier","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nans","family":"Florens","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Claude Bernard Lyon-1, Lyon Est, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Lemoine","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Claude Bernard Lyon-1, Lyon Est, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Dubourg","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Claude Bernard Lyon-1, Lyon Est, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Juillard","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Claude Bernard Lyon-1, Lyon Est, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitsum","family":"Guebre-Egziabher","sequence":"additional","affiliation":[{"name":"CarMeN Laboratory, INSERM U1060, INRA, Universit\u00e9 Claude Bernard Lyon 1, F-69500 Bron, France"},{"name":"Hospices Civils de Lyon, Department of Nephrology\u2013Hypertension-Dialysis, H\u00f4pital E. Herriot, F-69003 Lyon, France"},{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Claude Bernard Lyon-1, Lyon Est, F-69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/S0272-6386(98)70145-3","article-title":"Controlling the epidemic of cardiovascular disease in chronic renal disease: What do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease","volume":"32","author":"Levey","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"ref_2","first-page":"S16","article-title":"Epidemiology of cardiovascular disease in chronic renal disease","volume":"9","author":"Foley","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1525-139X.2009.00590.x","article-title":"The role of oxidative stress in chronic kidney disease","volume":"22","author":"Massy","year":"2009","journal-title":"Semin. Dial."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1097\/00041552-200311000-00004","article-title":"Oxidative stress in uremia","volume":"12","author":"Himmelfarb","year":"2003","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1111\/j.1440-1797.2012.01572.x","article-title":"Oxidative stress, anti-oxidant therapies and chronic kidney disease","volume":"17","author":"Small","year":"2012","journal-title":"Nephrology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Cachofeiro, V., Goicochea, M., de Vinuesa, S.G., Oubi\u00f1a, P., Lahera, V., and Lu\u00f1o, J. (2008). Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int. Suppl., S4\u2013S9.","DOI":"10.1038\/ki.2008.516"},{"key":"ref_7","first-page":"175","article-title":"Oxidative stress, inflammation and cardiovascular disease in chronic renal failure","volume":"21","author":"Cottone","year":"2008","journal-title":"J. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1093\/ndt\/gfg074","article-title":"Oxidative stress in end-stage renal disease: An emerging threat to patient outcome","volume":"18","author":"Locatelli","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.jrn.2006.04.015","article-title":"Oxidative stress: An accomplice to uremic toxicity?","volume":"16","author":"Mircescu","year":"2006","journal-title":"J. Ren. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1093\/ndt\/11.supp5.48","article-title":"Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions","volume":"11","author":"Requena","year":"1996","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0891-5849(91)90192-6","article-title":"Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes","volume":"11","author":"Esterbauer","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/0005-2760(90)90118-H","article-title":"4-Hydroxyhexenal: A lipid peroxidation product derived from oxidized docosahexaenoic acid","volume":"1043","author":"Holte","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/sj.bjp.0707395","article-title":"Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors","volume":"153","author":"Coatrieux","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1194\/jlr.M600340-JLR200","article-title":"Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals","volume":"48","author":"Bacot","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/carcin\/23.11.1781","article-title":"The major lipid peroxidation product, trans-4-hydroxy-2-nonenal, preferentially forms DNA adducts at codon 249 of human p53 gene, a unique mutational hotspot in hepatocellular carcinoma","volume":"23","author":"Hu","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1073\/pnas.89.10.4544","article-title":"Modification of histidine residues in proteins by reaction with 4-hydroxynonenal","volume":"89","author":"Uchida","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1021\/tx9000072","article-title":"Mass spectrometric characterization of protein modification by the products of nonenzymatic oxidation of linoleic acid","volume":"22","author":"Zhu","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"10521","DOI":"10.1021\/bi060535q","article-title":"Covalent adduction of human serum albumin by 4-hydroxy-2-nonenal: Kinetic analysis of competing alkylation reactions","volume":"45","author":"Szapacs","year":"2006","journal-title":"Biochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1021\/tx8000303","article-title":"Low-density lipoprotein has an enormous capacity to bind (E)-4-hydroxynon-2-enal (HNE): Detection and characterization of lysyl and histidyl adducts containing multiple molecules of HNE","volume":"21","author":"Annangudi","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1681\/ASN.2019111205","article-title":"CKD Increases Carbonylation of HDL and Is Associated with impaired antiaggregant properties","volume":"31","author":"Florens","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2010.03.015","article-title":"Trans-4-hydroxy-2-hexenal, a product of n-3 fatty acid peroxidation: Make some room HNE","volume":"49","author":"Long","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.cbi.2010.06.015","article-title":"Quantitative structure-activity relationship for 4-hydroxy-2-alkenal induced cytotoxicity in L6 muscle cells","volume":"188","author":"Pillon","year":"2010","journal-title":"Chem. Biol. Interact."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3474","DOI":"10.1021\/bi027172o","article-title":"Molecular basis of enzyme inactivation by an endogenous electrophile 4-hydroxy-2-nonenal: Identification of modification sites in glyceraldehyde-3-phosphate dehydrogenase","volume":"42","author":"Ishii","year":"2003","journal-title":"Biochemistry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1016\/S0021-9258(18)53699-1","article-title":"Inactivation of glucose-6-phosphate dehydrogenase by 4-hydroxy-2-nonenal. Selective modification of an active-site lysine","volume":"268","author":"Szweda","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1110\/ps.4400102","article-title":"Hydroxynonenal inactivates cathepsin B by forming Michael adducts with active site residues","volume":"11","author":"Crabb","year":"2002","journal-title":"Protein Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1021\/tx200084d","article-title":"Structural and functional changes in human insulin induced by the lipid peroxidation byproducts 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal","volume":"24","author":"Pillon","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/ki.1997.160","article-title":"Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure","volume":"51","author":"Miyata","year":"1997","journal-title":"Kidney Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/ndt\/15.suppl_1.7","article-title":"AGEs and carbonyl stress: Potential pathogenetic factors of long-term uraemic complications","volume":"15","author":"Zoccali","year":"2000","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1159\/000094305","article-title":"Elevated levels of alkanals, alkenals and 4-HO-alkenals in plasma of hemodialysis patients","volume":"26","author":"Alhamdani","year":"2006","journal-title":"Am. J. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"European uremic toxin work group normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1159\/000130658","article-title":"Oxidative stress in hemodialysis","volume":"161","author":"Himmelfarb","year":"2008","journal-title":"Contrib. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1002\/mnfr.200700451","article-title":"Oxidation products of polyunsaturated fatty acids in infant formulas compared to human milk\u2014A preliminary study","volume":"52","author":"Michalski","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1007\/s00125-017-4528-4","article-title":"Skeletal muscle insulin resistance is induced by 4-hydroxy-2-hexenal, a by-product of n-3 fatty acid peroxidation","volume":"61","author":"Soulage","year":"2018","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2174\/1389203716666150224150508","article-title":"Oxidative stress and antioxidative enzyme activities in chronic kidney disease and different types of renal replacement therapy","volume":"16","author":"Ciechanowski","year":"2015","journal-title":"Curr. Protein Pept. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1053\/j.jrn.2006.04.008","article-title":"Interrelationship between uremic toxicity and oxidative stress","volume":"16","author":"Rutkowski","year":"2006","journal-title":"J. Ren. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1744-9987.2010.00884.x","article-title":"New insight into the redox properties of uremic solute indoxyl sulfate as a pro- and anti-oxidant","volume":"15","author":"Miyamoto","year":"2011","journal-title":"Ther. Apher. Dial."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1002\/jps.22592","article-title":"Update on the pharmacokinetics and redox properties of protein-bound uremic toxins","volume":"100","author":"Watanabe","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ki.2012.448","article-title":"p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase","volume":"83","author":"Watanabe","year":"2013","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00092","DOI":"10.1002\/prp2.92","article-title":"p-Cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress","volume":"3","author":"Watanabe","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"S36","DOI":"10.1016\/j.freeradbiomed.2014.10.778","article-title":"The uremic toxin indoxyl sulfate acts as a pro- or antioxidant on LDL oxidation","volume":"75","author":"Praschberger","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.toxlet.2015.01.021","article-title":"Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK\/UCP2 signaling pathway","volume":"234","author":"Yang","year":"2015","journal-title":"Toxicol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3109\/10715762.2015.1125996","article-title":"The uremic toxin indoxyl sulfate exacerbates reactive oxygen species production and inflammation in 3T3-L1 adipose cells","volume":"50","author":"Saldanha","year":"2016","journal-title":"Free Radic. Res."},{"key":"ref_43","first-page":"755","article-title":"Potential contribution of monounsaturated fatty acids to cardiovascular risk in chronic kidney disease","volume":"128","author":"Mika","year":"2018","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/bj3300175","article-title":"Human glutathione transferase A4-4: An alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation","volume":"330","author":"Hubatsch","year":"1998","journal-title":"Biochem. J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1111\/j.1471-4159.2007.05175.x","article-title":"Trans-4-hydroxy-2-hexenal is a neurotoxic product of docosahexaenoic (22:6; n-3) acid oxidation","volume":"105","author":"Long","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1006\/bbrc.1998.8845","article-title":"Reduction of 4-hydroxynonenal and 4-hydroxyhexenal by retinal aldose reductase","volume":"247","author":"He","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1093\/clinchem\/45.10.1781","article-title":"Overexpression of erythrocyte glutathione S-transferase in uremia and dialysis","volume":"45","author":"Galli","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0272-6386(13)80013-3","article-title":"The role of reactive oxygen species in animal models of glomerular disease","volume":"19","author":"Diamond","year":"1992","journal-title":"Am. J. Kidney Dis."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Vlassara, H., Torreggiani, M., Post, J.B., Zheng, F., Uribarri, J., and Striker, G.E. (2009). Role of oxidants\/inflammation in declining renal function in chronic kidney disease and normal aging. Kidney Int. Suppl., S3\u2013S11.","DOI":"10.1038\/ki.2009.401"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3866","DOI":"10.1093\/ndt\/gfr386","article-title":"4-Hydroxy-2-hexenal-induced apoptosis in human renal proximal tubular epithelial cells","volume":"26","author":"Bae","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_51","first-page":"463","article-title":"Neutrophil chemotactic responses to aldehydes","volume":"36","author":"Curzio","year":"1982","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3109\/10715769409145636","article-title":"The lipid peroxidation product 4-hydroxynonenal is formed by--and is able to attract--rat neutrophils in vivo","volume":"20","author":"Schaur","year":"1994","journal-title":"Free Radic. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0098-2997(03)00009-8","article-title":"Basic aspects of the biochemical reactivity of 4-hydroxynonenal","volume":"24","author":"Schaur","year":"2003","journal-title":"Mol. Aspects Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/jcp.22189","article-title":"Advanced oxidation protein products inhibit differentiation and activate inflammation in 3T3-L1 preadipocytes","volume":"225","author":"Zhou","year":"2010","journal-title":"J. Cell. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0098-2997(03)00011-6","article-title":"Intracellular metabolism of 4-hydroxynonenal","volume":"24","author":"Siems","year":"2003","journal-title":"Mol. Aspects Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0098-2997(03)00012-8","article-title":"Fate of 4-hydroxynonenal in vivo: Disposition and metabolic pathways","volume":"24","author":"Alary","year":"2003","journal-title":"Mol. Aspects Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1210\/en.2011-1957","article-title":"The lipid peroxidation by-product 4-hydroxy-2-nonenal (4-HNE) induces insulin resistance in skeletal muscle through both carbonyl and oxidative stress","volume":"153","author":"Pillon","year":"2012","journal-title":"Endocrinology"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/9\/567\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:06:32Z","timestamp":1760177192000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/12\/9\/567"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":57,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["toxins12090567"],"URL":"https:\/\/doi.org\/10.3390\/toxins12090567","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,3]]}}}