Effect of the GABA derivative succicard on the lipid and carbohydrate metabolism in the offspring of rats with experimental preeclampsia in early and late ontogeny
- Authors: Muzyko E.A.1, Perfilova V.N.1, Nesterova A.A.2, Suvorin K.V.1, Tyurenkov I.N.1
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Affiliations:
- Volgograd State Medical University
- Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
- Issue: Vol 8, No 5 (2020)
- Pages: 325-335
- Section: Articles
- URL: https://journals.rcsi.science/2307-9266/article/view/111653
- DOI: https://doi.org/10.19163/2307-9266-2020-8-5-325-335
- ID: 111653
Cite item
Abstract
Maternal preeclampsia can bring about metabolic disorders in the offspring at different stages of ontogeny. Up to date, no ways of preventive pharmacological correction of lipid and carbohydrate metabolism disorders developing in different periods of ontogeny in the children born to mothers with this pregnancy complication, have been developed.
The aim of the experiment was to study the effect of the gamma-aminobutyric acid derivative succicard (22 mg/kg) and its reference drug pantogam (50 mg) administered per os in the course of treatment in puberty (from 40 to 70 days after birth), on the parameters of lipid and carbohydrate metabolism in the offspring of the rats with experimental preeclampsia, in different periods of ontogeny.
Materials and methods. To assess the activity of lipid and carbohydrate metabolism in the offspring, an oral glucose tolerance test was performed at 40 days, 3, 6, 12 and 18 months of age. The level of glycosylated hemoglobin was measured at the age of 6, 12, and 18 months, and the concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides were tested at 40 days, 3, 6, 12, and 18 months of age.
Results. The offspring of the rats with experimental preeclampsia, were found out to have lipid and carbohydrate metabolism disturbances during early (40 days and 3 months of age) and late (6, 12, and 18 months of age) ontogeny. In comparison with the offspring of healthy females, these disturbances were manifested by significantly higher levels of glucose revealed during the oral glucose tolerance test, by high glycosylated hemoglobin in males, and with elevated concentration of total cholesterol and triglycerides and a low level of high-density lipoprotein cholesterol in the negative control rats. Both the gamma-aminobutyric acid derivative succicard and its reference drug pantogam, reduced the negative effect of experimental preeclampsia on lipid and carbohydrate metabolism in the offspring in late ontogeny (6, 12 and 18 months of age). The effectiveness of succicard was either higher or comparable with pantogam.
Conclusion. Thus, the negative impact manifestations of experimental preeclampsia on lipid and carbohydrate metabolism, are revealed in the offspring in early (40 days and 3 months) and late (6, 12 and 18 months of age) ontogeny. The gamma-aminobutyric acid derivative succicard reduces the negative effect of experimental preeclampsia. Based on this finding, the drug implies the possibility of the development of a safe and highly effective medicine for preventive correction of lipid and carbohydrate metabolism disorders in the children born to mothers with preeclampsia.
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##article.viewOnOriginalSite##About the authors
Elena A. Muzyko
Volgograd State Medical University
Author for correspondence.
Email: muzyko.elena@mail.ru
ORCID iD: 0000-0003-0535-9787
postgraduate student of The Department of Pharmacology and Pharmacy of Institute of Continuing Medical and Pharmaceutical Education
Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131Valentina N. Perfilova
Volgograd State Medical University
Email: vnperfilova@mail.ru
ORCID iD: 0000-0002-2457-8486
Doctor of Science (Biology), Professor, Professor of The Department of Pharmacology and Pharmacy of Institute of Continuing Medical and Pharmaceutical Education
Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131Alla A. Nesterova
Pyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University
Email: aanesterova2013@gmail.com
ORCID iD: 0000-0003-3140-3016
Candidate of Science. (Medicine), Assistant Professor of The Department of Morphology
Russian Federation, 11, Kalinin Ave., Pyatigorsk, 357532Kirill V. Suvorin
Volgograd State Medical University
Email: kvsuvorin1@mail.ru
6th year student of The Pediatrics Faculty
Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131Ivan N. Tyurenkov
Volgograd State Medical University
Email: fibfuv@mail.ru
ORCID iD: 0000-0001-7574-3923
Corresponding Fellow of the RAS, Professor, The Head of The Department of Pharmacology and Pharmacy of Institute of Continuing Medical and Pharmaceutical Education
Russian Federation, 1, Pavshikh Bortsov Sq., Volgograd, 400131References
- Lu HQ, Hu R. Lasting Effects of Intrauterine Exposure to Preeclampsia on Offspring and the Underlying Mechanism. AJP Rep. 2019;9(3):e275–e291. doi: 10.1055/s-0039-1695004.
- Galina ТV, Devyatova ЕА, Gagayev ChG. Preeclamspia: new aspects of pathogenesis, concept, screening and prevention. Obstetrics and Gynecology: news, opinions, training. 2017;3:67–77. Russian
- Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275–289. doi: 10.1038/s41581-019-0119-6.
- tojanovska V, Scherjon SA, Plösch T. Preeclampsia As Modulator of Offspring Health. Biol Reprod. 2016;94(3):53. doi: 10.1095/biolreprod.115.135780.
- Lin S, Leonard D, Co MA, Mukhopadhyay D, Giri B, Perger L, Beeram MR, Kuehl TJ, Uddin MN. Pre-eclampsia has an adverse impact on maternal and fetal health. Transl Res. 2015;165(4):449–63. doi: 10.1016/j.trsl.2014.10.006.
- Wu CS, Nohr EA, Bech BH, Vestergaard M, Catov JM, Olsen J. Health of children born to mothers who had preeclampsia: a population-based cohort study. Am J Obstet Gynecol. 2009;201(3):269.e1–269.e10. doi: 10.1016/j.ajog.2009.06.060.
- Tumaeva Т.S., Balykova L.А. Features of Metabolic Processes in Children Born by Caesarean Section in the Early Adaptation Period: the Role of Cerebral Ischemia. Current Pediatrics. 2015;14(3):374–379. doi: 10.15690/vsp.v14i3.1373. Russian
- Alkabasova AA, Yevstifeeva GYu, Veterkova ZA, Sumenko VV, Krasikov SI, Sharapova NV. Description of the lipid spectrum of blood serum in infants suffering from intrauterine growth retardation. Vestnik of OSU. 2012;137(1):189-192. Russian
- Washburn L, Nixon P, Russell G, Snively BM, O’Shea TM. Adiposity in adolescent offspring born prematurely to mothers with preeclampsia. J Pediatr. 2013;162(5):912–7.e1. doi: 10.1016/j.jpeds.2012.10.044.
- Tyurenkov IN, Perfilova VN, Reznikova LB, Smirnova LA, Ryabukha AF, Sutchkov YeA, Kuznetsov KA. GABA derivatives citrocard and salifen reduce the intensity of experimental gestosis. Bulletin of Experimental Biology and Medicine. 2014;157(1):49–52. Russian
- Tyurenkov IN, Perfilova VN, Karamysheva VI, Popova TA, Lebedeva SA, Mikailova LI, Zhakupova GA. Gravidoprotective effect of phenibut in experimental preeclampsia. Experimental and Clinical Pharmacology. 2014;77(11):6–10. Russian
- Burtchinsky S. GABA-ergic agents in pharmacological therapy of chronic cerebral ischemia. International Neurological Journal. 2015;1(71):101–105. Russian
- Tyurenkov IN, Popova TA, Perfilova VN, Zhakupova GA, Ostrovsky OV, Lebedeva SA. Effect of RSPU-189 compound and sulodexide on placental mitochondrial respiration in female rats with experimental preeclampsia. SOJ Gynecology, obstetrics and women’s health. 2016;2(2):7. doi: 10.15226/2381-2915/2/2/00112. Russian
- Popova TA, Khusainova GH, Prokofiev II, Perfilova VN, Tyurenkov IN, Bagmetova VV, Malyuzhenko IV, Ganzikova NS, Dudchenko GP, Ostrovsky OV. Correction of alcohol-induced damage of cardiac and cerebral mitochondria with the derivatives of neuroactive aminoacids. Bulletin of Experimentral Biology and Medicine. 2020;2:176–181. Russian
- Tyurenkov IN. Search for therapeutical agents for treating neurodegenerative lesions among GABA derivatives. Journal of Volgograd State Medical University. 2011;S:32–34. Russian
- Voronina TA. Pantogam and pantogam are active. Pharmacological effects and mechanism of action. In the book: Pantogam and pantogam active. Clinical application and basic research. Ed. Kopelevich VM. M.: Triada Pharm 2009;11–30. Russian
- Spasov AA, Voronkova MP, Snigur GL, Tibirkova YeV, Proskurina IA. Instructional guidelines for preclinical study of oral pharmaceutical drugs for treating diabetes mellitus. In.: Guidelines for conducting preclinical studies of pharmaceutical drugs. Part 1. М.: Grif and K. 2012:944. Russian
- Paz Levy D, Sheiner E, Wainstock T, Sergienko R, Landau D, Walfisch A. Evidence that children born at early term (37–38 6/7 weeks) are at increased risk for diabetes and obesity-related disorders. Am J Obstet Gynecol. 2017;217(5):588.e1–588.e11. doi: 10.1016/j.ajog.2017.07.015.
- Khalyfa A, Cortese R, Qiao Z, Ye H, Bao R, Andrade J, Gozal D. Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice. J Physiol. 2017;595(8):2551–2568. doi: 10.1113/JP273570.
- Tokbergenova SM, Kalmenova PE, Ospanova ShM, Kemelbekov KS. Serum lipid spectrum was performed in neonates with cerebral ischemia. Vestnik KazNMU. 2013;4(2):200–201. Russian
- McDonnold M, Tamayo E, Kechichian T, Gamble P, Longo M, Hankins GD, Saade GR, Costantine MM. The effect of prenatal pravastatin treatment on altered fetal programming of postnatal growth and metabolic function in a preeclampsia-like murine model. Am J Obstet Gynecol. 2014;210(6):542.e1–7. doi: 10.1016/j.ajog.2014.01.010.
- Shah A, Reyes LM, Morton JS, Fung D, Schneider J, Davidge ST. Effect of resveratrol on metabolic and cardiovascular function in male and female adult offspring exposed to prenatal hypoxia and a high-fat diet. J Physiol. 2016;594(5):1465–82. doi: 10.1113/JP271133.
- Akhaphong B, Lockridge A, Jo S, Mohan R, Wilcox JA, Wing CR, Regal JF, Alejandro EU. Reduced uterine perfusion pressure causes loss of pancreatic β-cell area but normal function in fetal rat offspring. Am J Physiol Regul Integr Comp Physiol. 2018;315(6):R1220–R1231. doi: 10.1152/ajpregu.00458.2017.
- He J, Zhang A, Fang M, Fang R, Ge J, Jiang Y, Zhang H, Han C, Ye X, Yu D, Huang H, Liu Y, Dong M. Methylation levels at IGF2 and GNAS DMRs in infants born to preeclamptic pregnancies. BMC Genomics. 2013;14:472. doi: 10.1186/1471-2164-14-472.
- von Ehr J, von Versen-Höynck F. Implications of maternal conditions and pregnancy course on offspring’s medical problems in adult life. Arch Gynecol Obstet. 2016;294(4):673-9. doi: 10.1007/s00404-016-4178-7.
- Wang X, Wan L, Weng X, Xie J, Zhang A, Liu Y, Dong M. Alteration in methylation level at differential methylated regions of MEST and DLK1 in fetus of preeclampsia. Hypertens Pregnancy. 2018;37(1):1–8. doi: 10.1080/10641955.2017.1397689.
- Zvejniece L, Svalbe B, Veinberg G, Grinberga S, Vorona M, Kalvinsh I, Dambrova M. Investigation into stereoselective pharmacological activity of phenotropil. Basic Clin Pharmacol Toxicol. 2011;109(5):407–12. doi: 10.1111/j.1742-7843.2011.00742.x.
- Zvejniece L, Svalbe B, Vavers E, Makrecka-Kuka M, Makarova E, Liepins V, Kalvinsh I, Liepinsh E, Dambrova M. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity. Pharmacol Biochem Behav. 2017;160:21–29. doi: 10.1016/j.pbb.2017.07.009.
- Belousov YuB, Mukhina MA. Phenotropil – a new generation nootropic agent. Good Clinical Practice. 2005:3. Russian