CORRECTION OF ENDOTHELIAL DYSFUNCTION BY MOLECULAR HYDROGEN IN RATS WITH METABOLIC SYNDROME

Abstract

SUMMARY. Metabolic syndrome (MS) is characterized by insulin resistance, abdominal obesity, dyslipidemia, and hypertension, and is associated with the development of endothelial dysfunction manifested by reduced production of vasodilatory agents, increased levels of vasoconstrictors, and an imbalance of fibrinolytic regulators.

The aim – to investigate the effect of molecular hydrogen (H₂) on endothelial function in rats with experimentally induced MS.

Material and Methods. A total of 90 male Wistar rats were used and divided into three groups according to the duration of MS exposure (6, 12, and 20 weeks). MS was induced by a high-carbohydrate/high-fat diet. Correction was performed using molecular hydrogen-enriched water (0.6 ppm). Serum levels of prostacyclin, thromboxane A₂, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were measured using ELISA.

Results. In young rats exposed to MS for 6 weeks, alterations in endothelial function were minimal, and the effect of H₂ was negligible. At the intermediate stage of MS (12 weeks), a significant decrease in prostacyclin by 24 % and tPA by 52 % was observed compared with controls, accompanied by an increase in thromboxane A₂ by 39 % and PAI-1 by 96 %. Hydrogen administration partially restored these parameters: tPA increased by 53 %, while thromboxane A₂ and PAI-1 decreased by 20 % and 31 %, respectively. In older rats (20 weeks), the most pronounced changes occurred: prostacyclin decreased by 31 %, thromboxane A₂ increased by 54 %, PAI-1 by 120 %, and tPA showed excessive activation; H₂ restored or normalized these values by 19–30 %.

The findings demonstrate a phase-specific effect of H₂: its influence is limited at early stages, partial restoration of endothelial function is observed at the intermediate stage, and pronounced normalization or attenuation of excessive changes occurs in long-term MS. Biochemically, this effect may be explained by modulation of oxidative stress and inflammation through activation of the Nrf2/HO-1 pathway, reduction of ROS, inhibition of pro-inflammatory cascades (NF-κB, TLR4/MyD88), and restoration of fibrinolytic balance.

Conclusions. Molecular hydrogen effectively corrects endothelial dysfunction in rats with MS, exhibiting phase-specific activity, and may be considered a promising vasculoprotective agent for managing metabolic disorders.