Lactate dehydrogenase activity and carbohydrate metabolism under vanadium citrate exposure: Sex- and dose-dependent effects in rat tissues
- 1Department of Human and Animals Physiology, Biology Faculty of Ivan Franko National University of Lviv, Lviv, Ukraine
- 2Department of Pharmacy and Biology, Stepan Gzhytskyi National University of Veterinary Medicine and Biotechnologies of Lviv, Lviv, Ukraine
- 3Laboratory of Biochemistry of Animal Adaptation and Ontogenesis, Institute of Animal Biology NAAS, Lviv, Ukraine
Abstract
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 — lactate dehydrogenase (LDH) — 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 36–38 days at doses of 3, 12.5, and 50 μg 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 μg VCit/kg, while for males – 3 μg VCit/kg. The most significant changes in LDH activity were recorded in the pancreas at a dose of 50 μg V/kg, where the indicators decreased from 0.81 to 0.31 μmol/(min × mg protein) in females and from 1.02 to 0.28 μmol/(min × mg 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.
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BibTeX
@article{iskra2026lactate,
title = {{Lactate dehydrogenase activity and carbohydrate metabolism under vanadium citrate exposure: Sex- and dose-dependent effects in rat tissues}},
author = {Ruslana Iskra and Halyna Klymets and Iryna Oliynyk},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0357938},
url = {https://doi.org/10.1371/journal.pone.0357938},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Lactate dehydrogenase activity and carbohydrate metabolism under vanadium citrate exposure: Sex- and dose-dependent effects in rat tissues
AU - Ruslana Iskra
AU - Halyna Klymets
AU - Iryna Oliynyk
PY - 2026
DA - 2026/10/06
JO - PLOS One
DO - 10.1371/journal.pone.0357938
UR - https://doi.org/10.1371/journal.pone.0357938
AB - 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 — lactate dehydrogenase (LDH) — 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 36–38 days at doses of 3, 12.5, and 50 μg 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 μg VCit/kg, while for males – 3 μg VCit/kg. The most significant changes in LDH activity were recorded in the pancreas at a dose of 50 μg V/kg, where the indicators decreased from 0.81 to 0.31 μmol/(min × mg protein) in females and from 1.02 to 0.28 μmol/(min × mg 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.
SN - 1932-6203
ER -