Effect of diet-induced hypercholesterolemia on metabolic processes in the heart, liver, and pancreas in rats

Aim. To analyze the biochemical changes in the cells of the heart muscle, liver and pancreas, as well as to establish their pathogenetic significance in diet-induced experimental hypercholesterolemia.

Methods. The study was conducted on 65 outbred male rats. During the experiment, the animals were divided into groups: the first (control, n=30) — animals that were kept on a general vivarium diet; the second (experimental, n=35) — animals with diet-induced hypercholesterolemia for three months by keeping on a special diet. At the end of the experiment, the concentrations of pyruvic acid, lactate, reduced glutathione, the activity of glutathione reductase, and glutathione peroxidase were determined in the tissues by using biochemical methods. The Student's t-test was used for the experimental data of the samples after normality testing.

Results. The analysis of energy metabolism indicators in animals with hypercholesterolemia relative to the control group revealed a lower level of pyruvic acid in the heart muscle (0.29±0.03 mmol/mg protein; p ≤0.05) and liver (0.25±0.02 mmol/mg protein; p >0.001). A significantly higher lactate level was recorded in all tissues, most pronounced in the liver (6.73±0.6 mmol/mg protein; p ≤0.001). The results obtained indicate the predominance of the anaerobic glycolysis in the tissues and the accumulation of incomplete-oxidation products. The study of the key glutathione-linked enzymes in animals with hypercholesterolemia relative to the control showed a lower activity of glutathione reductase in the pancreas — 0.52±0.05 mmol/mg protein/min (p ≤0.001), as well as its higher activity in the liver — 0.297±0.03 mmol/mg protein/min (p ≤0.001) and heart — 13.58±1.4 mmol/mg protein/min (p >0.001). The activity of glutathione peroxidase and reduced glutathione in all organs remained practically unchanged, or the differences were insignificant. This trend indicates a violation of the antioxidant defense system and oxidative stress.

Conclusion. Changes in the metabolic link of adaptive-compensatory responses in the cells of the heart muscle, liver, and, most pronounced in the pancreas, indicate the role of the pancreas as a “target organ” in the pathogenesis of diet-induced hypercholesterolemia.