Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2025; 71(4): 29-37


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

L.Ya. Shtanova1, S.P. Vesеlsky1, P.I. Yanchuk1, R.A. Rozhnova2, V.S. Moskvina1, O.V. Shablykina1, E.M. Reshetnik1, O.V. Kravchenko3, V.P. Khilya1

  1. Taras Shevchenko National University of Kyiv
  2. Institute of the Macromolecular Chemistry of the NAS of Ukraine, Kyiv
  3. O.O. Bogomolets National Medical University, Kyiv
DOI: https://doi.org/10.15407/fz71.04.029


Abstract

Progress in understanding the extent and role of gastrointesti- nal dysfunction in Parkinson's disease (PD) has significantly advanced over the past decade. PD is believed to be associ- ated 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 benzodiaze pine 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.

Keywords: rotenone; parkinsonian syndrome; metresdiazenone; bile; bile lipids

References

  1. Deliz JR, Tanner CM, Gonzalez-Latapi P. Epidemiology of Parkinson's disease: An update. Curr Neurol Neurosci Rep. 2024;24(6):163-79.
  2. Chen Zh, Li G, Liu J. Autonomic dysfunction in Parkinson's disease: Implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis. 2020. 134:104700.
  3. Yang Y , Zhang Z. α-Synuclein pathology from the body to the brain: so many seeds so close to the central soil. Neural Regen Res. 2024;19(7):1463-72.
  4. Ben-Shlomo Y, Darweesh S, Llibre-Guerra J, Marras C, San Luciano M, Tanner C. The epidemiology of Parkinson's disease. Lancet. 2024;403(10423):283-92.
  5. Morris HR, Spillantini MG, Sue CM, Williams-Gray CH. The pathogenesis of Parkinson's disease. Lancet. 2024;403(10423):293-304.
  6. Li HY, Liu DS, Zhang YB, Rong H, Zhang XJ. The interaction between alpha-synuclein and mitochondrial dysfunction in Parkinson's disease. Biophys Chem. 2023;303:107122.
  7. Mori А, Imai Y, Hattori N. Lipids: Key players that modulate α-synuclein toxicity and neurodegeneration in Parkinson's disease. Int J Mol Sci. 2020;7;21(9):3301.
  8. Chia SJ,Tan E-K, Chao Y -X. Historical perspective: Models of Parkinson's disease. Int J Mol Sci. 2020;21(7):2464.
  9. Vijiaratnam N,Simuni T, Bandmann O, Morris HR, Foltynie T. Progress towards therapies for disease modification in Parkinson's disease. Lancet Neurol. 2021;20(7):559-72. Вплив похідного бензодіазепіну – метрездіазенону на ліпідний метаболізм у щурів з паркінсонічним синдромом 37
  10. Caputi V, Giron MC. Microbiome-gut-brain axis and toll-like receptors in parkinson's disease. Int J Mol Sci. 2018; 19:1689.
  11. Fonseca-Fonseca L,Wong-Guerra M, Ramírez-Sánchez J, Montano-Peguero Y , PadrónYaquis A, Rodríguez A, da Silva V , Costa S, Pardo-Andreu Y . JM-20, a novel hybrid molecule, protects against rotenone-induced neurotoxicity in experimental model of Parkinson's disease. Neurosci Lett. 2019;690:29-35.
  12. de Zárate AO, Pérez-Torralba M, Isidro IB, López C, Claramunt RM, Martínez-Casanova D, Sánchez-Vera I, González JJ, Lavandera JL. 1,5-Benzodiazepin2(3H)- ones: In vitro evaluation as antiparkinsonian agents. Antioxidants. 2021;10,1584.
  13. Shtanova LYa, Vesеlsky SP, Yanchuk PI, Tsymbalyuk OV , Moskvina VS, Shablykina OV , Moroz OF, V ovkun TV , Kravchenko ОV , Khilya VP. Purine and lipid metabolism in rats with a rotenone model of Parkinson's disease under the influence of methanindiazenone. Fiziol Zh. 2022;68(6):18-30.
  14. Shtanova LY ,Vesеlsky SP, Yanchuk PI, Tsymbalyuk OV , Moroz OF, ReshetnikEM, Moskvina VS, Shablykina OV , Kravchenko ОV , Khilya VP. Benzodiazepinе derivative methanindiazenone modulates lipid metabolism in the liver of rats with rotenone-induced Рarkinsonian syndrome. Fiziol Zh. 2023;69(6):77-87.
  15. Bonaz B. The gut-brain axis in Parkinson's disease. Rev Neurol (Paris). 2024;180(1-2):65-78.
  16. Reyes JF, Ekmark-Lewen S, Perdiki M, Klingstedt T, Hoffmann A, Wiechec E, Nilsson P. Accumulation of alpha-synuclein within the liver, potential role in the clearance of brain pathology associated with Parkinson's disease. Acta Neuropathol Commun. 2021;9(1):46.
  17. Wang X, Liang T, Mao Y, Li Z, Li X, Zhu X, Cao F, Zhang J. Nervonic acid improves liver inflammationin a mouse model of Parkinson's disease by inhibiting proinflammatory signaling pathways and regulating metabolic pathways. Phytomedicine. 2023;117:154911.
  18. Shablykina O, Krekhova O, Konovalenko А, Moskvina V , Khilya V . Interactionof 3-pyridyland 3-(imidazo[1,2-a] pyridin-2-yl) isocoumarins with hydrazine. Dop Natl Аkad Nauk Ukr. 2018;(12):71-8.
  19. Zeng X, Geng W, Jia J. Neurotoxin induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro. 2018;10:1759091418777438.
  20. Moroz OF, V eselskiy SP , Lyashchenko TP , Nuryshchenko NE. Changes of lipid components ratio in the rat bile after applying bombesin neuropeptide. Ukr Biochem J. 2009;81:52-58.
  21. Costa HN, Esteves AR, Empadinhas N, Cardoso SM. Parkinson's disease: A Multisystem disorder. Neurosci Bull. 2023;39(1):113-24.
  22. Higinbotham AS, Kilbane CW. The gastrointestinal tract and Parkinson's disease. Front Cell Infect Microbiol. 2024;15;13:1158986.
  23. Farooqui AA, Horrocks LA, Farooqui T. Glyce rophos-pholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipid. 2000;106(1):1-29.
  24. vanMeer G, Voelker D R &Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9:112-24.
  25. Markovinovic А, Greig J, Martín-Guerrero SM, Salam S, Paillusson S. Endoplasmic reticulum-mitochondria signaling in neurons and neurodegenerative diseases. J Cell Sci. 2022;135(3):jcs248534.
  26. Nieto СY, Yakhine-Diop SMS, Moreno-Cruz P, García МL, Pereira GA, Morales-García JA, Niso-Santano M. Changes in liver lipidomic profile in G2019SLRRK2 mouse model of Parkinson's disease. Cells. 2023;12:806.
  27. Rossmeisl M, Medrikova D, van Schothorst E, Pavlisova J, Kuda O, Hensler M, Bardova K, Flachs P. Omega-3 phospholipids from fish suppress hepatic steatosis by integrated inhibition of biosynthetic pathways in dietary obese mice. Biochim Biophys Acta. 2014;1841(2):267-78.
  28. Hong X, Guo W, Shanshan L. Lower blood lipid level is associated with the occurrence of Parkinson's disease: A meta-analysis and systematic review. Int J Clin Pract. 2022;9:2022:9773038.
  29. Alrouji M, Al-Kuraishy HM, Abdu Ali Al-Mahammadawy A-K, Al-Gareeb AI, Saad HM, Batiha El-Saber G. The potential role of cholesterol in Parkinson's disease neuropathology: perpetrator or victim. Neurol Sci. 2023;44(11):3781-94.
  30. Gudala К, Bansal D, Muthyala Н. Role of serum cholesterol in Parkinson's disease: a meta-analysis of evidence. J Parkinson Dis. 2013;3(3):363-70.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2025.