Ukr.Biochem.J. 2020; Volume 92, Issue 6, Nov-Dec, pp. 85-94

doi: https://doi.org/10.15407/ubj92.06.085

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

L. Ya. Shtanova1,2*, P. I. Yanchuk1, S. P. Vesеlsky1,
O. V. Tsymbalyuk1, T. V. Vovkun2, V. S. Moskvina2, O. V. Shablykina2,
S. L. Bogza2, V. N. Baban1, A. A. Kravchenko3, V. P. Khilya2

1Institute of High Technologies, Taras Shevchenko National University of Kyiv, Ukraine;
2Taras Shevchenko National University of Kyiv, Ukraine;
3Chuiko Institute of Surface Chemistry, National Academy of Sciences, Kyiv;
*e-mail: shtanova@ukr.net

Received: 5 March 2020; Accepted: 13 November 2020

Parkinson’s disease (PD) is a chronic and progressive age-related neurodegenerative disorder. Accumulation of α-synuclein aggregates, oxidative stress, mitochondrial dysfunction and lipid metabolism  disturbance are thought to be the key violations at PD pathogenesis. Despite long-time  research the causes of PD occurrence are not yet clear. We investigated the influence of diazepinon, a new derivative of benzodiazepine, on liver tissue respiration (LTR), serum lipid content and  behavioral parameters of rats with modeled PD induced by intraperitoneal injections of 2.0 mg/kg rotenone (ROT) within 28 days. LTR was assessed using the polarograph LP-9. Blood samples for biochemical analysis were collected from the inferior vena cava. The behavioral parameters of rats were studied by the open field test. We showed  that in rats with ROT – induced PD the coefficient of liver oxygen consumption was decreased by 33.5% (P < 0.001), the serum content of phospholipids, cholesterol, cholesterol esters, free fatty acids and triglycerides was reduced by 21.4% (P < 0.001), 28.8% (P < 0.001), 26.8% (P < 0.001), 30.3% (P < 0.01) and 41.5% (P < 0.001) respectively and the motor disorders were detected. Diazepinone application resulted in a full recovery of  LTR,  serum concentration of phospholipids, partial recovery of serum free fatty acids and triglycerides content and significant improvement of motor behavior. However  diazepinone did not affect the reduced concentration of cholesterol and cholesterol esters in the serum of rats with simulated PD.

Keywords: , , , ,


References:

  1. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124(8):901-905. PubMed, CrossRef
  2. Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386(9996):896-912. PubMed, CrossRef
  3. Mazzoni P, Shabbott B, Cortés JC. Motor control abnormalities in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012;2(6):a009282. PubMed, PubMedCentral, CrossRef
  4. Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464-474. PubMed, CrossRef
  5. Gustafsson H, Nordström A, Nordström P. Depression and subsequent risk of Parkinson disease: A nationwide cohort study. Neurology. 2015;84(24):2422-2429. PubMed, PubMedCentral, CrossRef
  6. Burré J. The synaptic function of α-synuclein. J Parkinsons Dis. 2015;5(4):699-713. PubMed, PubMedCentral, CrossRef
  7. Sherer TB, Greenamyre JT. Oxidative damage in Parkinson’s disease. Antioxid Redox Signal. 2005;7(5-6):627-629. PubMed, CrossRef
  8. Park JS, Davis RL, Sue CM. Mitochondrial Dysfunction in Parkinson’s Disease: New Mechanistic Insights and Therapeutic Perspectives. Curr Neurol Neurosci Rep. 2018;18(5):21. PubMed, PubMedCentral, CrossRef
  9. Xicoy H, Wieringa B, Martens GJM. The Role of Lipids in Parkinson’s Disease. Cells. 2019;8(1):27. PubMed, PubMedCentral, CrossRef
  10. 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-phosphate-dehydrogenase and the pentose phosphate pathway in paraquat toxicity. ACS Chem Biol. 2014;9(9):2032-2048. PubMed, PubMedCentral, CrossRef
  11. Doria M, Maugest L, Moreau T, Lizard G, Vejux A. Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson’s disease. Free Radic Biol Med. 2016;101:393-400. PubMed, CrossRef
  12. Dorszewska J, Prendecki M, Lianeri M, Kozubski W. Molecular Effects of L-dopa Therapy in Parkinson’s Disease. Curr Genomics. 2014;15(1):11-17. PubMed, PubMedCentral, CrossRef
  13. Fonseca-Fonseca LA, Wong-Guerra M, Ramírez-Sánchez J, Montano-Peguero Y, Padrón Yaquis AS, Rodríguez AM, da Silva VDA, Costa SL, Pardo-Andreu GL, Núñez-Figueredo 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. PubMed, CrossRef
  14. Nickel B, Jakovlev V, Szelenyi I. The effect of flupirtine, various analgesics and muscle relaxants on skeletal muscle tone in the conscious rat. Arzneimittelforschung. 1990;40(8):909-911. PubMed
  15. Khilya VP, Yanchuk PI, Shtanova LYa, Vesеlsky SP, Vovkun TV, Tsymbalyuk OV, Moskvina VS, Shablykina OV, Bogza SL. The evaluation of 2.3-diazepine influence on tissue respiration of the liver and its exocrine function in rats with a rotenone model of Parkinson’s disease. Biopolym Cell. 2019;35(5):356-370.  CrossRef
  16. Sherer TB, Betarbet R, Testa CM, Seo BB, Richardso JR, Kim JH, Miller GW, Yagi T, Matsuno-Yagi A, Greenamyre JT. Mechanism of toxicity in rotenone models of Parkinson’s disease. J Neurosci. 2003;23(34):10756-10764. PubMed, PubMedCentral, CrossRef
  17. Zeng XS, Geng WS, Jia JJ. Neurotoxin-Induced Animal Models of Parkinson Disease: Pathogenic Mechanism and Assessment. ASN Neuro. 2018;10:1759091418777438. PubMed, PubMedCentral, CrossRef
  18. Gallagher  D, Belmonte D, Deurenberg P, Wang Z, Krasnow N, Pi-Sunyer FX, Heymsfield SB. Organ-tissue mass measurement allows modeling of REE and metabolically active tissue mass. Am J Physiol. 1998;275(2):E249-E258. PubMed, CrossRef
  19. Shablykina OV, Krekhova OF, Konovalenko АS, Moskvina VS, Khilya VP. Interaction of 3-pyridyland 3-(imidazo[1,2-a]pyridin-2-yl)isocoumarins with hydrazine. Dopov Nac Аkad Nauk Ukr. 2018;(12):71-78.  CrossRef
  20. Chang YT, Luo XG, Ren Y. Behavior alteration and damage of dopaminergic neurons of substantia nigra caused by rotenone in rats. Jiepouxue Yanjiu Jingzhan. 2011;7:60-62.
  21. Bures J, Burešová O, Huston JP. Techniques and Basic Experiments for the Study of Brain and Behavior. Elsevier, 1976. 290 p. CrossRef
  22. Berezovsky VA. Oxygen tension in animal and human tissues. Kyiv: Naukova dumka, 1975. 276 p. (In Russian).
  23. Tsybenko VA, Egorova LS, Mikhaylova NV, Zhakhalova LA, Dubiley  TA. Neurogenic control of oxidative metabolism in the liver. Fiziol Zh SSSR Im I M Sechenova. 1988;74(5):737-745. (In Russian). PubMed
  24. Vovkun TV, Yanchuk PI, Shtanovа LYa, Veselsky SP, Filimonova NB, Komarov IV. Corvitin modulates the content of lipids in rat liver bile. Ukr Biochem J. 2019; 91(6):112-121. PubMed
  25. Panov A, Dikalov S, Shalbuyeva N, Taylor G, Sherer T, Greenamyre JT. Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. J Biol Chem. 2005;280(51):42026-42035. PubMedCrossRef
  26. Graham SF, Rey  NL, Yilmaz A, Kumar P, Madaj Z, Maddens M, Bahado-Singh RO, Becker K, Schulz E, Meyerdirk LK, Steiner JA, Ma J, Brundin P. Biochemical profiling of the brain and blood metabolome in a mouse model of prodromal Parkinson’s disease reveals distinct metabolic profiles. J Proteome Res. 2018;17(7):2460-2469. PubMed, PubMedCentral, CrossRef
  27. Miyake Y, Sasaki S, Tanaka K, Fukushima W, Kiyohara C, Tsuboi Y, Yamada T, Oeda T, Miki T, Kawamura N, Sakae N, Fukuyama H, Hirota Y, Nagai M. Dietary fat intake and risk of Parkinson’s disease: a case-control study in Japan. J Neurol Sci. 2010;288(1-2):117-122.
    PubMed, CrossRef
  28. Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. Dietary intakes of fat and risk of Parkinson’s disease. Am J Epidemiol. 2003;157(11):1007-1014. PubMed, CrossRef
  29. Schulte EC, Altmaier E, Berger HS, Do KT, Kastenmüller G, Wahl S, Adamski J, Peters A, Krumsiek J, Suhre K, Haslinger B, Ceballos-Baumann A, Gieger C, Winkelmann J. Alterations in lipid and inositol metabolisms in two dopaminergic disorders. PLoS One. 20165;11(1):e0147129. PubMed, PubMedCentral, CrossRef
  30. Huang X, Auinger P, Eberly S, Oakes D, Schwarzschild M, Ascherio A, Mailman R, Chen H. Serum cholesterol and the progression of Parkinson’s disease: results from DATATOP. PLoS One. 2011;6(8):e22854. PubMed, PubMedCentral, CrossRef
  31. Liu JP, Tang Y, Zhou S, Toh BH, McLean C, Li H. Cholesterol involvement in the pathogenesis of neurodegenerative diseases. Mol Cell Neurosci. 2010;43(1):33-42. PubMed,CrossRef
  32. Gudala K, Bansal D, Muthyala H. Role of serum cholesterol in Parkinson’s disease: a meta-analysis of evidence. J Parkinsons Dis. 2013;3(3):363-370. PubMed, CrossRef
  33. Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology. 2008;70(21):1972-1979. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.