EFFECT OF A BENZODIAZEPINE DERIVATIVE, METRESDIAZENONE, ON LIPID METABOLISM IN RATS WITH PARKINSONIAN SYNDROME

Progress in understanding the extent and role of gastrointestinal dysfunction in Parkinson's disease (PD) has significantly advanced over the past decade. PD is believed to be associated not only with the loss of dopaminergic neurons in the substantia nigra of the midbrain, but also with a range of peripheral metabolic changes, including those in the liver. Autonomic dysfunction is recognized as a key non-motor feature of PD. This study aimed to investigate the effect of a novel benzodiazepine derivative, metresdiazenone, on the lipid composition of bile in a rotenone-induced rat model of Parkinsonian syndrome (PS). Compared to control animals, rotenone exposure led to a decrease in bile concentrations of phospholipids, cholesterol, cholesterol esters, and triglycerides by 23.6%, 24.5%, 29.3%, and 38.1%, respectively, with no significant change in free fatty acid content. Administration of metresdiazenone at a dose of 1 mg/kg restored bile lipid levels nearly to baseline: phospholipids (100%), cholesterol (82.2%), cholesterol esters (87.5%), and triglycerides (82.1%). At higher doses (2 and 4 mg/kg), bile concentrations of phospholipids exceeded control values by 12.5% and 25.3%, cholesterol by 12.4% and 11.7%, cholesterol esters by 11.3% and 19.5%, triglycerides by 20.7% and 31.2%, and free fatty acids by 10.1% and 14.2%, respectively. These findings indicate that metresdiazenone at 1 mg/kg effectively restores impaired lipid metabolism in the liver in the rotenone model of PS, while higher doses lead to a marked increase in triglyceride levels.