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: diazepinone, liver tissue respiration, motor behavior, Parkinson’s disease, serum lipids
References:
- Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017;124(8):901-905. PubMed, CrossRef
- Kalia LV, Lang AE. Parkinson’s disease. Lancet. 2015;386(9996):896-912. PubMed, CrossRef
- 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
- Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol. 2009;8(5):464-474. PubMed, CrossRef
- 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
- Burré J. The synaptic function of α-synuclein. J Parkinsons Dis. 2015;5(4):699-713. PubMed, PubMedCentral, CrossRef
- Sherer TB, Greenamyre JT. Oxidative damage in Parkinson’s disease. Antioxid Redox Signal. 2005;7(5-6):627-629. PubMed, CrossRef
- 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
- Xicoy H, Wieringa B, Martens GJM. The Role of Lipids in Parkinson’s Disease. Cells. 2019;8(1):27. PubMed, PubMedCentral, CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- Bures J, Burešová O, Huston JP. Techniques and Basic Experiments for the Study of Brain and Behavior. Elsevier, 1976. 290 p. CrossRef
- Berezovsky VA. Oxygen tension in animal and human tissues. Kyiv: Naukova dumka, 1975. 276 p. (In Russian).
- 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
- 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
- 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. PubMed, CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
