Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson’s disease

Shtanova, L. Ya.; Yanchuk, Petro I.; Veselsky, S.P.

doi:10.15407/ubj92.06.085

Cited by 2 publications

(3 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results show that in rats with simulated PD, the level of ECHOL in the bile decreased almost twice, which may be due to a marked decrease in the CHOL synthesis in the liver in parkinsonian rats, and therefore decreased the number of its esterified molecules. We have previously shown a decrease in the concentration of CHOL and ECHOL in the plasma of rats with ROT-induced PD, as well as other plasma lipids, in particular PL, FFA, and TG [27]. Our experiments, at least for CHOL and TG, agree with the findings of other researchers who believe that the low content of these compounds in the plasma of patients with PD is a risk factor in its development [28].…”

Section: Influence Of Dp On Bile Lipids Content In Ratssupporting

confidence: 91%

“…A possible reason for the decrease in bile lipid content of Parkinsonic rats may be the increased use of FFA as an energy source to compensate for energy deficiency in conditions where the ATP-synthesizing function of mitochondria is blocked. The results of motor function investigation in rats with ROT-induced PD and the effect of DP on voluntary motility were published earlier [27].…”

Section: Influence Of Dp On Bile Lipids Content In Ratsmentioning

confidence: 99%

See 1 more Smart Citation

Corrective effects of benzodiazepine derivative – diazepinone on purine and lipid metabolism in the liver of rats with Parkinson’s disease

Shtanova¹,

Yanchuk²,

Veselsky³

et al. 2021

Fiziol Zh

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The cause of PD is not fully understood, and effective treatments still do not exist. It is believed that oxidative stress, mitochondrial dysfunction, and impaired lipid metabolism may underlie the pathogenesis of PD. Bile contains the breakdown products of various compounds that form in hepatocytes. This study aimed to evaluate the effect of a new benzodiazepine derivative - diazepinone (DP) on purine and lipid metabolism in the liver of rats with PD caused by rotenone (ROT) by studying the composition of bile. The concentration of ATP, ADP, AMP, xanthine, hypoxanthine, phospholipids (PL), cholesterol (CHOL), cholesterol esters (ECHOL), free fatty acids (FFA), and triglycerides (TG) was quantified in bile samples by thin-layer chromatography. Our findings suggested that the ratio of AMP/ ATP in bile increased almost threefold under the influence of ROT, and with DP, it exceeded the norm by only 1.6 times. ROT also increased the content of xanthine and hypoxanthine by 28.6% and 66.7%, respectively. DP did not affect the increased xanthine content relative to control but significantly reduced the level of hypoxanthine (up to 22.2%, above normal). In addition, ROT reduced the content of bile PL, CHOL, ECHOL, TG by 23.9%, 38.6%, 47.5%, 39.2 %, respectively. Under the influence of the DP, all the above indicators returned to the level of control. Thus, diazepinone improves both the metabolism of purines and lipids in the liver of rats with ROT-simulated PD. This drug may become a therapeutic agent for treating PD and possibly other neurodegenerative diseases in the future.

show abstract

Section: Influence Of Dp On Bile Lipids Content In Ratssupporting

confidence: 91%

Section: Influence Of Dp On Bile Lipids Content In Ratsmentioning

confidence: 99%

Corrective effects of benzodiazepine derivative – diazepinone on purine and lipid metabolism in the liver of rats with Parkinson’s disease

Shtanova¹,

Yanchuk²,

Veselsky³

et al. 2021

Fiziol Zh

View full text Add to dashboard Cite

show abstract

“…Notably, Fonseca-Fonseca, et al [12] demonstrated that benzodiazepine derivatives protect the mitochondria of both rat neurons and liver from rotenone-induced damage. In our prior research, we documented lipid level alterations in the blood of rotenone-induced PS rats and identified changes in bile lipid fractions, pointing to suppressed hepatic metabolic processes in PS [13]. Thus, this study aims to investigate the potential protective effects of a new benzodiazepine derivative, methanediazenone, on the lipid metabolism in the liver of rotenone-induced PS rats.…”

Section: Introductionmentioning

confidence: 96%

Benzodiazepinе derivative methanindiazenone modulates lipid metabolism in the liver of rats with rotenone-induced Parkinson’s syndrome

Shtanova,

Vesеlsky,

Yanchuk

et al. 2023

Fiziol Zh

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a neurodegenerative condition for which the exact causes remain elusive, and no effective treatments currently exist. The pathogenesis of PD is believed to involve oxidative stress, mitochondrial dysfunction, and lipid metabolism disorders. A benzodiazepine derivative JM-20 has demonstrated protective effects on mitochondria in both neurons and peripheral tissues of rats with rotenoneinduced Parkinson’s syndrome (PS). This study aimed to analyze bile composition and assess the impact of a new benzodiazepine derivative, methanindiazenone, on lipid metabolism in the liver of rats subjected to the rotenone model of PS. The results indicated that, compared to the control group, bile concentration of phospholipids, cholesterol, cholesterol esters, and triglycerides decreased by 24.3, 26.2, 25.8, and 27.5%, respectively. With methanindiazenone treatment at doses of 0.5 and 1.0 mg/kg, all these metrics reverted to the control level. However, in the rotenone+methanindiazenone 2.0 mg/kg group, the levels of phospholipids, cholesterol, and cholesterol esters (except for triglycerides) surpassed the control values by 33, 28.1, 28.4 and 33.5%, respectively. Methanindiazenone positively impacted the motor behavior of rats with the rotenone model of PS and enhanced their survival rates. Therefore, at doses of 0.5 and 1.0 mg/kg, methanindiazenone not only improved lipid metabolism in the liver but also the overall well-being of rats with the rotenone model of PS. However, a 2 mg/kg dose of methanindiazenone displayed toxic effects, as seen from the increased content of phospholipids, cholesterol, and cholesterol esters in bile. Hence, methanindiazenone holds potential as a therapeutic agent for PS and possibly other neurodegenerative diseases related to lipid metabolism impairment, but its use should be limited to doses of 0.5 and 1.0 mg/kg.

show abstract

Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson’s disease

Cited by 2 publications

References 28 publications

Corrective effects of benzodiazepine derivative – diazepinone on purine and lipid metabolism in the liver of rats with Parkinson’s disease

Corrective effects of benzodiazepine derivative – diazepinone on purine and lipid metabolism in the liver of rats with Parkinson’s disease

Benzodiazepinе derivative methanindiazenone modulates lipid metabolism in the liver of rats with rotenone-induced Parkinson’s syndrome

Contact Info

Product

Resources

About