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

Fiziologichnyi Zhurnal

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. 2022; 68(6): 18-30


Purine and lipid metabolism in rats with a rotenone model of Parkinson’s disease under the influence of methanindiazenone

L.Ya. Shtanova1, S.P. Vesеlsky1, P.I. Yanchuk2, O.V. Tsymbalyuk2, V.S. Moskvina1, O.V. Shablykina1, O.F. Moroz4, T.V. Vovkun1, О.V. Kravchenko3, V.P. Khilya1

  1. Faculty of Chemistry, Taras Shevchenko National University of Kyiv, Ukraine
  2. Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine
  3. O.O. Bogomolets National Medical University, Kyiv, Ukraine
  4. Education and Scientific Center “Institute of Biology and Medicine”. Taras Shevchenko National University of Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz68.06.018


Abstract

This study aims to evaluate the effect of methanindiazenone (МD), a new benzodiazepine derivative, on the levels of purine metabolites and lipids in the blood plasma of rats with rotenone (ROT) induced Parkinson’s disease (PD). The concentrations of ATP, ADP, AMP, xanthine, hypoxanthine, phospholipids (PL), cholesterol (CHOL), cholesterol esters (ECHOL), free fatty acids (FFA), and triglycerides (TG) were quantified in plasma samples by thin-layer chromatography. Our data demonstrate that in rats with ROT-induced PD the AMP/ATP ratio in plasma increased by 2.5 times compared to the control, and this indicator returned to normal values under the influence of MD. ROT also increased the concentration of xanthine and hypoxanthine by 26.7% (Р < 0.001) and 42.4% (Р < 0.001), respectively, compared to the control. MD restored xanthine concentration to 86.7% of the control level and returned hypoxanthine concentration to normal values. Besides, ROT reduced the blood plasma concentrations of PL, CHOL, ECHOL, FFA, TG by 22%, (Р < 0.001), 18% (Р < 0.001), 25% (Р < 0.001), 28% (Р < 0.001), 33% (Р < 0.001), respectively. Under the influence of MD, such indicators as the blood plasma concentration of PL, CHOL, FFA returned to control levels. Оur results suggest that MD improves the metabolism of both purines and lipids in rats with ROT-induced PD.

Keywords: rotenone; Parkinson’s disease; benzodiazepine derivatives; motor behavior; blood plasma; purines; lipids.

References

  1. Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson disease: A review. JAMA. 2020; 323(6):548-60. CrossRef PubMed
  2. Muddapu VR, Dharshini SAP, Chakravarthy VS, Gromiha MM. Neurodegenerative diseases - is metabolic deficiency the root cause? Front. Neurosci. 2020;14:213. CrossRef PubMed PubMedCentral
  3. Bloem BR, Okun MS, Klein C. Parkinson's disease. Lancet. 2021;397(10291):2284-303. CrossRef PubMed
  4. Möhler H, Fritschy JM, Rudolph U. A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002;300(1):2-8. CrossRef PubMed
  5. Dauvilliers Y, Schenck CH, Postuma RB, Iranzo A, Luppi P-H, Plazzi G, Montplaisir J, Boeve B. REM sleep behaviour disorder. Nat Rev Dis Primers. 2018;4(1):19. CrossRef PubMed
  6. Fonseca-Fonseca L, Wong-Guerra M, Ramírez-Sánchez J, Montano-Peguero Y, Padrón Yaquis 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. 2019b;690:29-35. CrossRef PubMed
  7. Ana Ortíz de Zárate, Marta Pérez-Torralba, Iñigo Bonet Isidro, Concepción López, Rosa M Claramunt, Diana Martínez-Casanova, Isabel Sánchez-Vera, Jesús Jiménez- González and José Luis Lavandera. 1,5-Benzodiazepin- 2(3H)-ones: In vitro evaluation as antiparkinsonian agents. Antioxidants. 2021;10,1584. CrossRef PubMed PubMedCentral
  8. Xicoy H, Wieringa B, Martens G. The role of lipids in Parkinson's disease. Cells. 2019;8(1):27. CrossRef PubMed PubMedCentral
  9. Lei S, Zavala-Flores L, Garcia-Garcia A, Nandakumar R, Huang Y, Madayiputhiya N, Stanton RC, Dodds ED, Powers R, Franco R. Alterations in energy/ redox metabolism induced by mitochondrial and environmental toxins: a specific role for glucose-6- phosphatedehydrogenase and the pentose phosphate pathway in paraquat toxicity. AC S Chem Biol. 2014; 9(9): 2032-48. CrossRef PubMed PubMedCentral
  10. Xiaoxue Fu, Yu Wang, Xiaofeng He , Hongyu Li , Hong Liu and Xiangyang Zhan Fu. A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson's disease. Lipids Health Disease. 2020;19:97. CrossRef PubMed PubMedCentral
  11. Xue Hong, Wenting Guo, Shanshan Li. Lower blood lipid level is associated with the occurrence of Parkinson's disease: A meta-analysis and systematic review. Int J Clin Pract. 2022;9773038. CrossRef PubMed PubMedCentral
  12. Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurlogy. 2008;70(21):1972-79. CrossRef PubMed
  13. Shtanova LYa, Yanchuk PI, Veselsky SP, Tsymbalyuk OV, Vovkun TV, Moskvina VS, Shablykina OV, Bogza SL, Baban VN, Kravchenko AA, Khilya VP. Diazepinone effect on liver tissue respiration and serum lipid content in rats with a rotenone model of Parkinson's disease. Ukr Biochem J. 2020;92, Issue 6:85-94.
  14. Shtanova LYa, Yanchuk PI, Veselsky SP, Tsymbalyuk OV, Vovkun TV, Moskvina VS, Shablykina OV, Kravchenko AA, Baban VN, Khilya VP. Corrective effects of benzodiazepine derivative - diazepinone on purine and lipid metabolism in the liver of rats with Parkinson's disease. Fiziol Zh. 2021;67(4):64-75. CrossRef
  15. Shablykina O, Krekhova O, Konovalenko A, Moskvina V, Khilya V. Interaction of 3-pyridyl and 3-(imidazo[1,2-a] pyridin-2-yl) isocoumarins with hydrazine. Dopov Nac Akad Nauk Ukr. 2018;(12):71-8. CrossRef
  16. Zeng X, Geng W, Jia J. Neurotoxin induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro. 2018;10:1759091418777438. CrossRef PubMed PubMedCentral
  17. Vovkun TV, Yanchuk PI, Shtanova LYa, Veselsky SP, Filimonova NB, Komarov IV. Corvitin modulates the content of lipids in rat liver bile. Ukr Biochem J. 2019; 91(6):112-21. CrossRef
  18. Maidanyuk A, Imedadze S. Determination of the adenine series components by densitometry of chromatograms in ultraviolet light. Bull Kyiv National Taras Shevchenko Univ. 2004;42-43:2-13 [Ukrainian].
  19. Angeline MS, Chaterjee P, Anand K, Ambasta RK, Kumar P. Rotenone-induced parkinsonism elicits behavioral impairments and differential expression of parkin, heat shock proteins and caspases in the rat. Neuroscience. 2012:291-301. CrossRef PubMed
  20. Cunnane SC, Trushina E, Morland C, Prigione A, Casadesus G, Andrews ZB, Beal MF, Bergersen LH, Brinton RD, de la Monte S, et al. Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19:609-33. CrossRef PubMed PubMedCentral
  21. Milane L, Trivedi M, Singh A, Talekar M, Amiji M. Mitochondrial biology, targets, and drug delivery. J Contr Release. 2015;207:40-58. CrossRef PubMed
  22. Xu J, Minobe E, Kameyama M. Ca2+ dyshomeostasis links risk factors to neurodegeneration in Parkinson's disease. Front Cell Neurosci. 2022;16: 867385. Published online 2022. CrossRef PubMed PubMedCentral
  23. Grünewald A, Kumar KR, Sue CM. New insights into the complex role of mitochondria in Parkinson's disease. Prog Neurobiol. 2019;177:73-93. CrossRef PubMed
  24. Saxena U. Bioenergetics failure in neurodegenerative diseases: back to the future. Expert Opin Ther Targets. 2012;16(4):351-4. CrossRef PubMed
  25. Li L, Nadanaciva S, Berger Z, Shen W, Paumier K, Schwartz J, Mou K, Loos P, Milici AJ, Dunlop J. Human A53T α-Synuclein causes reversible deficits in mitochondrial function and dynamics in primary mouse cortical neurons. PLoS ONE. 2013;8(12):e85815. CrossRef PubMed PubMedCentral
  26. Nunez-Figueredo Y, Pardo-Andreu G L, Ramírez-Sánchez J, Delgado-Hernández R, Ochoa-Rodríguez E, Verdecia- Reyes Y, Naal Z, Muller A P, Portela L V, Souza D O. Antioxidant effects of JM-20 on rat brain mitochondria and synaptosomes: mitoprotection against Ca2+-induced mitochondrial impairment. Brain Res Bull. 2014;109:68-76. CrossRef PubMed
  27. Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurol. 2015;14(6):625-39. CrossRef PubMed
  28. Pathak D, Shields LY, Mendelsohn BA, Haddad D, Lin W, Gerencser AA, Kim H, Brand MD, Edwards RH. The role of mitochondrially derived ATP in synaptic vesicle recycling. JBiol Chem. 2015;290(37):22325-36. CrossRef PubMed PubMedCentral
  29. Bonora M, Patergnani S, Rimessi A, De Marchi E, Suski J, Bononi A, Giorgi C. ATP synthesis and storage. Purinergic Signal. 2012;8(3):343-57. CrossRef PubMed PubMedCentral
  30. Palmer G, Horgan D, Tisdale H, Singer T, Beinert H. Studies on the respiratory chain-linked reduced nicotinamide adenine dinucleotide dehydrogenase. XIV. Location of the sites of inhibition of rotenone, barbiturates, and piericidin by means of electron paramagnetic resonance spectroscopy. J Biol Chem. 1968;243(4):844-7. CrossRef PubMed
  31. Dănău A, Dumitrescu L, Lefter A and Popescu BO. Serum uric acid levels in Parkinson's disease: A cross-sectional electronic medical record database: Study from a Tertiary Referral Centre in Romania. Medicina 2022;58:245. CrossRef PubMed PubMedCentral
  32. Yakhine-Diop S, Morales-García J, Niso-Santano M, González-Polo R, Uribe-Carretero E, Martinez- Chacon G, Durand S, Maiuri M, Aiastui A, Zulaica M, RuízMartínez J, de Munain A, Pérez-Tur J, Pérez-Castillo A, Kroemer G, Bravo-San Pedro J, Fuentes J. Metabolic alterations in plasma from patients with familial and idiopathic Parkinson's disease. Aging (Albany NY). 2020;12(17):16690-708. CrossRef PubMed PubMedCentral
  33. Farooqui AA, Horrocks LA, Farooqui T. Glycerophos- pholipids in brain: their metabolism, incorporation into membranes, functions, and involvement in neurological disorders. Chem Phys Lipids. 2000;106:1-29. CrossRef PubMed
  34. D'Ascenzo N, Antonecchia E, Angiolillo A, Bender V, Camerlenghi M, Xie Q, Metabolomics of blood reveals age-dependent pathways in Parkinson's disease. Cell Biosci. 2022;12(1):102. CrossRef PubMed PubMedCentral
  35. Keran Wanga, Zhehui Luoa, Chenxi Lia, Xuemei Huangb, Eric J Shiromac, Eleanor M Simonsickc, Honglei Chena. Blood cholesterol decreases as Parkinson's disease develops and progresses. J Parkinson's Disease. 2021;11:1177-86. CrossRef PubMed
  36. Liu Q, Trotter J, Zhang J, Peters MM, Cheng H, Bao J, Han X, Weeber EJ, Bu G. Neuronal LRP1 knockout in adult mice leads to impaired brain lipid metabolism and progressive, age-dependent synapse loss and neurodegeneration. J Neurosci. 2010;30(50):17068-78. CrossRef PubMed PubMedCentral

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