{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:53:08Z","timestamp":1791309188866,"version":"4.3.1"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Vanadium (V) is a potential insulinomimetic that can modulate carbohydrate metabolism, but its biological effects are sensitive to chemical form, concentration, and sex. Chelation of vanadium with organic ligands, in particular citrate, allows to increase its bioavailability and optimize pharmacokinetic properties. The aim of the study was to evaluate tissue-, dose-, and sex-dependent changes in physiological parameters and activity of the key glycolytic enzyme \u2014 lactate dehydrogenase (LDH) \u2014 under the influence of vanadium citrate. The study was conducted on 6-week-old Wistar rats of both sexes. The animals received vanadium citrate orally for 36\u201338 days at doses of 3, 12.5, and 50 \u03bcg VCit\/kg body weight. LDH activity in skeletal muscle, liver, kidney, and pancreas was investigated. No pronounced toxic effect on physiological parameters was detected: body weight dynamics corresponded to age norms, no behavioral changes were observed. LDH activity demonstrated pronounced sexual dimorphism and depended on the dose received. It was established that the optimal dose, which provides a modulating effect without signs of metabolic stress, for females is 12.5 \u03bcg VCit\/kg, while for males \u2013 3 \u03bcg VCit\/kg. The most significant changes in LDH activity were recorded in the pancreas at a dose of 50 \u03bcg V\/kg, where the indicators decreased from 0.81 to 0.31 \u03bcmol\/(min\u2009\u00d7\u2009mg protein) in females and from 1.02 to 0.28 \u03bcmol\/(min\u2009\u00d7\u2009mg protein) in males. The effect of vanadium citrate on carbohydrate metabolism, as well as its dose-, tissue- and sex-specific nature, is likely determined by a dual action: the insulin-like effect of vanadium (redirecting pyruvate to oxidation) and the allosteric inhibition of glycolysis by the citrate ligand (substrate limitation for LDH). The obtained results emphasize the importance of considering sex and dose in the research and development of metabolically active compounds.<\/jats:p>","DOI":"10.1371\/journal.pone.0357938","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:24:47Z","timestamp":1791307487000},"page":"e0357938","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lactate dehydrogenase activity and carbohydrate metabolism under vanadium citrate exposure: Sex- and dose-dependent effects in rat tissues"],"prefix":"10.1371","volume":"21","author":[{"given":"Ruslana","family":"Iskra","sequence":"first","affiliation":[{"name":"Biology Faculty of Ivan Franko National University of Lviv","place":["Lviv, Ukraine"],"department":["Department of Human and Animals Physiology"]},{"name":"Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies of Lviv","place":["Lviv, Ukraine"],"department":["Department of Pharmacy and Biology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halyna","family":"Klymets","sequence":"additional","affiliation":[{"name":"Institute of Animal Biology NAAS","place":["Lviv, Ukraine"],"department":["Laboratory of Biochemistry of Animal Adaptation and Ontogenesis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2487-1022","authenticated-orcid":true,"given":"Iryna","family":"Oliynyk","sequence":"additional","affiliation":[{"name":"Institute of Animal Biology NAAS","place":["Lviv, Ukraine"],"department":["Laboratory of Biochemistry of Animal Adaptation and Ontogenesis"]},{"name":"Lviv Medical University","place":["Lviv, Ukraine"],"department":["Department of Physical and Chemical Disciplines"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"3","key":"pone.0357938.ref001","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1152\/japplphysiol.00296.2001","article-title":"Gender differences in glucose kinetics and substrate oxidation during exercise near the lactate threshold","volume":"92","author":"BC Ruby","year":"2002","journal-title":"J Appl Physiol (1985)"},{"issue":"3","key":"pone.0357938.ref002","doi-asserted-by":"crossref","DOI":"10.1088\/1748-605X\/add3e5","article-title":"Recent advances in anti-tumor mechanisms and biological applications of vanadium compounds","volume":"20","author":"X Dang","year":"2025","journal-title":"Biomed Mater"},{"key":"pone.0357938.ref003","doi-asserted-by":"crossref","first-page":"5772","DOI":"10.1021\/ic010276n","article-title":"Vanadium(IV)-citrate complex interconversions in aqueous solutions. 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