{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:39:49Z","timestamp":1760060389895,"version":"build-2065373602"},"reference-count":108,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kerscher\u2019sche Stiftung","award":["SZ_FP_008.18","SZ_FP_164.20"],"award-info":[{"award-number":["SZ_FP_008.18","SZ_FP_164.20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Dicarbonyls and advanced glycation end-products (AGEs) contribute to oxidative stress, inflammation, and complications in type 2 diabetes mellitus (T2DM). Menaquinone-7 (MK-7), a vitamin K2 subtype, has shown benefits for glucose tolerance and vascular health in some studies. We evaluated the impact of MK-7 on dicarbonyls, free AGEs, and protein nitration\/oxidation adducts in a rat model of T2DM. Methods: Male heterozygous (fa\/+, control) and homozygous (fa\/fa, diabetic) Zucker Diabetic Fatty rats were fed a diabetogenic diet without or with MK-7 for 12 weeks. After sacrifice, plasma dicarbonyls as well as plasma and urinary levels of free AGEs and protein nitration\/oxidation adducts were quantified by isotope dilution tandem mass spectrometry. Results: Diabetic rats showed significantly increased plasma glyoxal, 3-deoxyglucosone, and fructosyl-lysine with non-significant trends toward increased methylglyoxal-derived hydroimidazolone and methionine sulfoxide, as well as reductions in methylglyoxal and dityrosine. Urinary carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine (all significant), and dityrosine (non-significant) were elevated in diabetic rats; glucosepane (non-significant) was reduced. MK-7 supplementation reduced no measured parameter but was associated with non-significant further increases in plasma glyoxal-derived hydroimidazolone, carboxyethyl-lysine, carboxymethyl-lysine, fructosyl-lysine, 3-nitrotyrosine, and methionine sulfoxide, as well as in urinary glyoxal-derived hydroimidazolone, carboxyethyl-lysine, fructosyl-lysine, and 3-nitrotyrosine, in diabetic rats. Correlation analysis revealed significant associations between glucose, dicarbonyls, AGEs, and oxidative markers. Conclusions: High-dose MK-7 supplementation did not improve dicarbonyl stress, AGE burden, or protein nitration\/oxidation. With respect to available scientific evidence and our observations, the combination of glycemia-driven amplification of glycation and oxidative stress, as well as MK-7-induced glutathione depletion, were likely causative.<\/jats:p>","DOI":"10.3390\/nu17172733","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:32Z","timestamp":1756080572000},"page":"2733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Menaquinone-7 Supplementation Increases Multiple Advanced Glycation End-Products and Oxidation Markers in Zucker Diabetic Fatty Rats"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8824-5990","authenticated-orcid":false,"given":"Ingo","family":"Mrosewski","sequence":"first","affiliation":[{"name":"MVZ MDI Limbach Berlin, Aroser Allee 84, 13407 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3232-4515","authenticated-orcid":false,"given":"Thomas","family":"Fleming","sequence":"additional","affiliation":[{"name":"Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"},{"name":"German Center for Diabetes Research (DZD), Helmholtz Center Munich, Ingolst\u00e4dter Landstrasse 1, 85764 Neuherberg, Germany"},{"name":"Joint Heidelberg-IDC Translational Diabetes Program, Internal Medicine I, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-9532","authenticated-orcid":false,"given":"Gundula","family":"Schulze-Tanzil","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Werner","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-9743","authenticated-orcid":false,"given":"Clemens","family":"G\u00f6gele","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeriya","family":"Mantel","sequence":"additional","affiliation":[{"name":"MVZ MDI Limbach Berlin, Aroser Allee 84, 13407 Berlin, Germany"},{"name":"Department V\u2014Life Sciences and Technology, Berlin University of Applied Sciences and Technology, Luxemburger Str. 10, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Kokozidou","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Paracelsus Medical University, Nuremberg and Salzburg, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bertsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, Nuremberg General Hospital, Paracelsus Medical University, Prof. Ernst Nathan Str. 1, 90419 Nuremberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/ame2.12030","article-title":"Comparative medical characteristics of ZDF-T2DM rats during the course of development to late stage disease","volume":"1","author":"Pang","year":"2018","journal-title":"Anim. 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