Original Articles

PEROXIREDOXIN AND ARACHIDONATE 15-LIPOXYGENASE AS DETERMINANTS OF LIPID PEROXIDATION IN OBESE YOUNG MEN

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Published: May 19 2026
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Obesity is characterized by chronic inflammation and oxidative stress that is associated with lipid peroxidation. We investigated the relationships among peroxiredoxin (an antioxidant enzyme), arachidonate 15-lipoxygenase (15-LOX; a pro-oxidant enzyme), and F2-isoprostanes (a marker of lipid peroxidation) in young obese males. This case-control study compared 135 obese males (body mass index [BMI]≥30 kg/m2) with 135 age-matched lean controls (BMI 18.5-24.9 kg/m2). Peroxiredoxin activity was measured fluorometrically; 15-LOX and F2-isoprostane concentrations were measured using the Enzyme-Linked Immunosorbent Assay (ELISA). Anthropometric and clinical parameters (glucose, hemoglobin A1c [HbA1c], and high-sensitivity C-reactive protein [hs-CRP]) were assessed. Receiver operating characteristic (ROC) analysis determined optimal diagnostic cut-offs. Obese participants showed significantly reduced peroxiredoxin activity (31±3.7 vs. 55±7.2 U/L), elevated 15-LOX (96.95±11.5 vs. 55.22±6.7 pg/mL), and increased F2-isoprostanes (53.7±5.7 vs. 17.35±2.2 pg/mL; all p<0.001). ROC analysis demonstrated excellent diagnostic performance: F2-isoprostane (area under the curve [AUC]=0.988; sensitivity=94.8%; specificity=91.1%), 15-LOX (AUC=0.986, sensitivity=97.0%, specificity=87.4%), and peroxiredoxin (AUC=0.958, sensitivity=100%, specificity=71.1%). Obesity induces a redox imbalance characterized by impaired antioxidant defense, enhanced enzymatic lipid oxidation, and pronounced lipid peroxidation. The high discriminative capacity of these biomarkers (AUC>0.95) reflects their sensitivity to the profound oxidative metabolic differences that distinguish obese from lean individuals.

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1. Sharma A, Sekhon S, Sandhu JS. Association of Body Fat Percentage, Body Mass Index, and Waist Circumference With Hemodynamics: Insights from a Healthy Adult Population. Cureus 2025;17.
2. Varra FN, Varras M, Varra VK, Theodosis-Nobelos P. Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation mediating treatment options. Mol Med Rep 2024;29:95.
3. Feng Y, Wang Y, Deng Y, et al. Crosstalk between perivascular adipose tissue and adipocyte-derived peptide in the pathogenesis of diabetic cardiomyopathy. Cardiovasc Diabetol 2025;24:332.
4. Engin A. Reappraisal of Adipose Tissue Inflammation in Obesity. Adv Exp Med Biol 2024;1460:297-327.
5. Alta’ee AH, Hadwan MH, Almashhedy LA. The balance between superoxide dismutase and catalase activities in sera of obese Iraqi men. EuroMed Biomed J 2015;10:197-202.
6. Lee JY, Han K, Kim J, et al. Association Between Metabolic Syndrome and Young-Onset Dementia: A Nationwide Population-Based Study. Neurology 2025;104:e213599.
7. Aravapally PS, Chandrasekar N, Verma A, Shah RP. Strategic approaches to assess and quantify the oxidative stress biomarkers in complex biological systems. Bioanalysis 2025;17:561-74.
8. Boldeanu L, Văduva CC, Caragea DC, et al. Association between serum 8-iso-prostaglandin F2α as an oxidative stress marker and immunological markers in a cohort of preeclampsia patients. Life 2023;13:2242.
9. Awari A, Kaushik D, Kumar A, et al. Obesity Biomarkers: Exploring Factors, Ramification, Machine Learning, and AI‐Unveiling Insights in Health Research. MedComm 2025;6:e70169.
10. Almashhedy LA, Fadhil HA, Alsalman AR, et al. Low levels of peroxiredoxins are associated with high iron content and lipid peroxidation in seminal plasma from asthenozoospermic infertile men. Endocr Metab Sci 2023;12:100137.
11. Khalifa HH, Hadwan MH. Simple method for the assessment of peroxiredoxin activity in biological samples. Chem Data Collect 2020;27:100376.
12. Hussein MJ, Hadwan MH. Fluorometric Protocol for Estimating Peroxiredoxin Activity in Biological Tissues. J Fluoresc 2023;33:721-30.
13. Benatzy Y, Palmer MA, Brüne B. Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology. Front Pharmacol 2022;13:1042420.
14. Kwon HJ, Kim SN, Kim YA, Lee YH. The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling. Cell Death Dis 2016;7:e2285.
15. Ferreira AV, Alarcon-Barrera JC, Domínguez-Andrés J, et al. Fatty acid desaturation and lipoxygenase pathways support trained immunity. Nat Commun 2023;14:7385.
16. Wittwer J, Hersberger M. The two faces of the 15-lipoxygenase in atherosclerosis. Prostaglandins Leukot Essent Fatty Acids 2007;77:67-77.
17. Mohsin NY, Demir H, Hadwan MH, et al. A New Fluorescent Method for Measuring Peroxiredoxin Enzyme Activity Using Monobromobimane. J Fluoresc 2025;35:6357-65.
18. Ozkaya DY, Haymana C, Demirci I, et al. MOTS-C levels ın ındividuals with and without obesity and ıts association with ınflammation, insulin resistance and endothelial dysfunction. Arch Endocrinol Metab 2025;69:e250063.
19. Stancill JS, Corbett JA. The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage. Front Endocrinol (Lausanne) 2021;12:718235.
20. Gao S, Zhou L, Lu J, et al. Cepharanthine Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Mice via Inhibiting 15‐Lipoxygenase‐1‐Mediated Microglia and Endothelial Cell Ferroptosis. Oxid Med Cell Longev 2022;2022:4295208.
21. Su HY, Tsai YC, Tsai HP, Lin CL. Zileuton, a 5-lipoxygenase inhibitor, attenuates haemolysate-induced BV-2 cell activation by suppressing the MyD88/NF-κB pathway. Int J Mol Sci 2022;23:4910.
22. Samovich SN, Mikulska‐Ruminska K, Dar HH, et al. Strikingly high activity of 15‐lipoxygenase towards di‐polyunsaturated arachidonoyl/adrenoyl‐phosphatidylethanolamines generates peroxidation signals of ferroptotic cell death. Angew Chem Int Ed Engl 2024;63:e202314710.
23. Ma XH, Liu JH, Liu CY, et al. ALOX15-launched PUFA-phospholipids peroxidation increases the susceptibility of ferroptosis in ischemia-induced myocardial damage. Signal Transduct Target Ther 2022;7:288.
24. Tyurina YY, Tian H, Dar HH, et al. 15-Lipoxygenase-dependent radiomitigation by NO●-Donors suppresses ferroptosis in intestinal Epithelium: Multiomics MS imaging and LC-MS evidence. Redox Biol 2025:103777.
25. Kuhn H, Banthiya S, van Leyen K. Mammalian lipoxygenases and their biological relevance. Biochim Biophys Acta 2015;1851:308-30.
26. Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature 2014;510:92-101.
27. Godson C, Mitchell S, Harvey K, et al. Cutting edge: lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages. J Immunol 2000;164:1663-7.
28. Brink C, Dahlén SE, Drazen J, et al. International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors. Pharmacol Rev 2003;55:195-227.
29. Uderhardt S, Krönke G. 12/15-lipoxygenase during the regulation of inflammation, immunity, and self-tolerance. J Mol Med 2012;90:1247-56.
30. Sears DD, Miles PD, Chapman J, et al. 12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice. PloS One 2009;4:e7250.
31. Benatzy Y, Palmer MA, Brüne B. Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology. Front Pharmacol 2022;13:1042420.
32. Park WH. Eicosanoids and inflammation: a delicate balance of pro-inflammatory and pro-resolving mediators. Biochem Pharmacol 2025:117662.
33. Patrono C, Falco A, Davì G. Isoprostane formation and inhibition in atherothrombosis. Curr Opin Pharmacol 2005;5:198-203.
34. Mieczkowski K, Bakiri L, Martins BS, et al. Fatty acid-binding protein 5 aggravates psoriasis and psoriasis-like disease through ferroptosis. Cell Death Differ 2025:1-2.
35. Wang B, Wang Y, Zhang J, et al. ROS-induced lipid peroxidation modulates cell death outcome: mechanisms behind apoptosis, autophagy, and ferroptosis. Arch Toxicol 2023;97:1439-51.
36. Ramasubbu K, Devi Rajeswari V. Impairment of insulin signaling pathway PI3K/Akt/mTOR and insulin resistance induced AGEs on diabetes mellitus and neurodegenerative diseases: a perspective review. Mol Cell Biochem 2023;478:1307-24.
37. Chen B, Li T, Wu Y, et al. Lipotoxicity: A New Perspective in Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes 2025;18:1223-37.
38. Onu A, Trofin DM, Tutu A, et al. Integrative Strategies for Preventing and Managing Metabolic Syndrome: The Impact of Exercise and Diet on Oxidative Stress Reduction – A Review. Life 2025;15:757.

How to Cite



PEROXIREDOXIN AND ARACHIDONATE 15-LIPOXYGENASE AS DETERMINANTS OF LIPID PEROXIDATION IN OBESE YOUNG MEN. (2026). EuroMediterranean Biomedical Journal, 21. https://doi.org/10.4081/embj.2026.486