The effect of a high-fat diet and phytocomposition on the activity of matrix metalloproteinases and the content of a tissue inhibitor of metalloproteinase-3 in the of rats liver

The aim of the study was to study the effect of phytocomposition (PhC) on the regulation of liver extracellular matrix metabolism in rats fed a high-fat diet (HFD). Materials and methods. The study was performed on male Wistar rats (n=81 weighted 240-280 g). After adaptation, the animals were randomly divided into groups: the first received a standard vivarium diet (StD, control); 2 - aqueous suspension of PhC (StD+PhC); 3 - HFD; 4 - HFD+PhC. After 4 and 7 weeks of experiment, the content of hyaluronan, a tissue inhibitor of metalloproteinase-3 (TIMP-3), hypoxia-inducible factor 1α (HIF-1α), the activity of matrix metalloproteinases (MMPs), and α2-macroglobulin (α2-MG) were measured in the liver. Results. In the StD+PhC group, the hyaluronan content was increased in both follow-up periods, MMP activity elevated - after 4 weeks, TIMP-3 content - after 7 weeks relative to the control. In the HFD group, the content of hyaluronan, TIMP-3, the activity of MMP, α2-MG was increased at both periods and the content of HIF-1α was increased after 7 weeks relative to the control. The contents of HIF-1α and hyaluronan after 7 weeks, TIMP-3 and α2-MG activity in both periods exceeded these of the StD+PhC group. In the HFD+PhC group, the hyaluronan content after 7 weeks of treatment corresponded to that of the control group but it turned out to be lower compared the data of the StD+PhC and HFD groups. The activity of MMP in both periods and α2-MG after 7 weeks is higher than in the control group. The increased levels of TIMP-3 and HIF-1α after 4 weeks corresponded to the data of the control after 7 weeks. By the end of the experiment, the levels of hyaluronan, TIMP-3, and HIF-1α were reduced relative to the HFD group. Conclusion. At the end of the experiment, the content of hyaluronan and TIMP-3 remained elevated in the StD+PhC group. The HFD group in both post-treatment states was characterized by liver fibrosis and tissue hypoxia linked with enhanced activity of not only degrading enzymes, but also enzymes controlling their activity increased. In the HFD+PhC group, there are no signs of tissue hypoxia and fibrosis due to increased MMP and α2-MG activity.