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Vol 7, No 1 (2022)
Original article
Published online: 2022-03-31
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Metabolic syndrome and losartan treatment effects in adult and pubertal rats

Larysa Borysivna Bondarenko1, Ganna Mykhailivna Shayakhmetova1, Tetiana Anatoliivna Karatsuba1, Anatoliy Vasyliovych Matvienko1, Valentyna Mykolaivna Kovalenko1
·
Medical Research Journal 2022;7(1):66-73.
Affiliations
  1. SI “Institute of Pharmacology & Toxicology National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine

open access

Vol 7, No 1 (2022)
ORIGINAL ARTICLES
Published online: 2022-03-31

Abstract

Introduction: Comparative estimation of losartan treatment effects in adult and pubertal rats with metabolic syndrome (MS).

Material and methods: MS model was induced by full replacement of drinking water with 20% fructose solution at Wistar male rats of two age categories: young animals of 21–23 days age (50–70 g) and adults (160–180 g). Clinical hematology and biochemistry tests, blood pressure measurement, chromatin DNA fragmentation, and liver morphological investigations were carried out after 60 days of MS modeling and losartan treatment.

Results: Effects of losartan on blood clotting time, lipid metabolism, and DNA fragmentation were more pronounced in pubertal rats, while more profound influence on high-density lipoprotein (HDL) contents, pancreas, and visceral fat relative weights was found in adults.

Conclusions: In pubertal and adult rats with MS, losartan effects were age-dependent for lipid metabolism indices, blood clotting time, nuclear DNA fragmentation, relative organs weights, and liver morphologic structure. Losartan treatment normalized blood pressure independently of age, while its effects on other parameters in adults and young rats differed not only in their degree of manifestation but also in their very nature.

Abstract

Introduction: Comparative estimation of losartan treatment effects in adult and pubertal rats with metabolic syndrome (MS).

Material and methods: MS model was induced by full replacement of drinking water with 20% fructose solution at Wistar male rats of two age categories: young animals of 21–23 days age (50–70 g) and adults (160–180 g). Clinical hematology and biochemistry tests, blood pressure measurement, chromatin DNA fragmentation, and liver morphological investigations were carried out after 60 days of MS modeling and losartan treatment.

Results: Effects of losartan on blood clotting time, lipid metabolism, and DNA fragmentation were more pronounced in pubertal rats, while more profound influence on high-density lipoprotein (HDL) contents, pancreas, and visceral fat relative weights was found in adults.

Conclusions: In pubertal and adult rats with MS, losartan effects were age-dependent for lipid metabolism indices, blood clotting time, nuclear DNA fragmentation, relative organs weights, and liver morphologic structure. Losartan treatment normalized blood pressure independently of age, while its effects on other parameters in adults and young rats differed not only in their degree of manifestation but also in their very nature.

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Keywords

metabolic syndrome, losartan, pubertal, adult, rats

About this article
Title

Metabolic syndrome and losartan treatment effects in adult and pubertal rats

Journal

Medical Research Journal

Issue

Vol 7, No 1 (2022)

Article type

Original article

Pages

66-73

Published online

2022-03-31

Page views

4855

Article views/downloads

302

DOI

10.5603/MRJ.a2022.0011

Bibliographic record

Medical Research Journal 2022;7(1):66-73.

Keywords

metabolic syndrome
losartan
pubertal
adult
rats

Authors

Larysa Borysivna Bondarenko
Ganna Mykhailivna Shayakhmetova
Tetiana Anatoliivna Karatsuba
Anatoliy Vasyliovych Matvienko
Valentyna Mykolaivna Kovalenko

References (30)
  1. Swislocki ALM, Siegel D, Jialal I. Pharmacotherapy for the metabolic syndrome. Curr Vasc Pharmacol. 2012; 10(2): 187–205.
  2. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004; 350(23): 2362–2374.
  3. Zimmet P, Alberti G, Kaufman F, et al. International Diabetes Federation Task Force on Epidemiology and Prevention of Diabetes. Global and societal implications of the diabetes epidemic. Lancet. 2007; 369(9579): 2059–2061.
  4. Chu PY, Campbell MJ, Miller SG, et al. Anti-hypertensive drugs in children and adolescents. World J Cardiol. 2014; 6(5): 234–244.
  5. Webb NJA, Wells TG, Shahinfar S, et al. A randomized, open-label, dose-response study of losartan in hypertensive children. Clin J Am Soc Nephrol. 2014; 9(8): 1441–1448.
  6. Bondarenko LB, Shayakhmetova G, Voronina A, et al. Losartan effects on liver cytochromes CYP3A, CYP2C and CYP2E1 functioning at metabolic syndrome in young and adult rats. Medical Research Journal. 2019; 4(2): 72–79.
  7. Iwamura A, Fukami T, Hosomi H, et al. CYP2C9-mediated metabolic activation of losartan detected by a highly sensitive cell-based screening assay. Drug Metab Dispos. 2011; 39(5): 838–846.
  8. Choi DH, Li C, Choi JS. Effects of myricetin, an antioxidant, on the pharmacokinetics of losartan and its active metabolite, EXP-3174, in rats: possible role of cytochrome P450 3A4, cytochrome P450 2C9 and P-glycoprotein inhibition by myricetin. J Pharm Pharmacol. 2010; 62(7): 908–914.
  9. Abdulla MH, Sattar MA, Abdullah NA, et al. The contribution of α1B-adrenoceptor subtype in the renal vasculature of fructose-fed Sprague-Dawley rats. Eur J Nutr. 2011; 50(4): 251–260.
  10. Khromov OS, Dobrelya NV. Experimental study of phosphatidyl choline liposomes as new hipotensive. Bulletin of Dnipropetrovsk University, 2008; 1(16): 197–203.
  11. Romeis B. Mikroskopische Technik. Foreign Literature. Inostrannaya literatura. 1953: 248–252.
  12. Piers E. Histochemistry. Foreign Literature. Inostrannaya literatura. 1962: 962.
  13. Mannervik B, Jemth P. The Glutathione Pathway. Measurement of Glu- tathione Transferases. Costa LG, Hodgson E, Lawrence DA, Ozolins TR, Reed DJ, Greenlee WF, editors. Current Protocols in Toxicology. N. In: Costa LG, Hodgson E, Lawrence DA, Ozolins TR, Reed DJ, Greenlee WF. ed. Current Protocols in Toxicology. John Wiley & Sons Inc, New York 2005: 2758.
  14. Bondarenko LB, Karatzuba T, Shayakhmetova G, et al. Specificity of metabolic syndrome model reproduction at pubertal and adult male rats. Romanian Journal of Diabetes Nutrition and Metabolic Diseases. 2015; 22(3): 251–260.
  15. el-Batran SA, el-Shenawy SM, Nofal SM, et al. Studies on the glycemic and lipidemic effect of monopril and losartan in normal and diabetic rats. Pharmacol Res. 2004; 50(2): 131–136.
  16. Luchtefeld M, Bandlow N, Tietge UJF, et al. Angiotensin II type 1-receptor antagonism prevents type IIA secretory phospholipase A2-dependent lipid peroxidation. Atherosclerosis. 2007; 194(1): 62–70.
  17. Gaafar AG, Abo-Youssef AM, Khalaf MM, et al. Protective effects of vitamin D and losartan in complete Freund's adjuvant-induced arthritis in rats. Pak J Pharm Sci. 2019; 32(2): 593–600.
  18. Abdel El-Gaphar OA, Abo-Youssef AM, Abo-Saif AA. Effect of losartan in complete freund's adjuvant-induced arthritis in rats. Iran J Pharm Res. 2018; 17(4): 1420–1430.
  19. Kamińska M, Mogielnicki A, Stankiewicz A, et al. Angiotensin II via AT1 receptor accelerates arterial thrombosis in renovascular hypertensive rats. J Physiol Pharmacol. 2005; 56(4): 571–585.
  20. Spence SG, Cukierski MA, Manson JM, et al. Defining the susceptible period of developmental toxicity for the AT1-selective angiotensin II receptor antagonist losartan in rats. Teratology. 1995; 51(6): 367–382.
  21. Wang X, Lu Y, Cederbaum AI. Induction of cytochrome P450 2E1 increases hepatotoxicity caused by Fas agonistic Jo2 antibody in mice. Hepatology. 2005; 42(2): 400–410.
  22. Vartanian V, Lowell B, Minko IG, et al. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc Natl Acad Sci U S A. 2006; 103(6): 1864–1869.
  23. Mercer JR, Cheng KK, Figg N, et al. DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome. Circ Res. 2010; 107(8): 1021–1031.
  24. Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Gerontol. 2009; 44(10): 625–633.
  25. Bondarenko L, Shayakhmetova G, Karatsuba T, et al. Age dependent effects of metformin in Wistar albino male rats with metabolic syndrome. Rom J Diabetes Nutr Metab Dis. 2018; 25: 47–58.
  26. Kumar D, Zimpelmann J, Robertson S, et al. Tubular and interstitial cell apoptosis in the streptozotocin-diabetic rat kidney. Nephron Exp Nephrol. 2004; 96(3): e77–e88.
  27. Erol A, Erol A. Metabolic syndrome is a real disease and premalignant state induced by oncogenic stresses to block malignant transformation. Med Hypotheses. 2010; 74(6): 1038–1043.
  28. Ray SD, Kamendulis LM, Gurule MW, et al. Ca2+ antagonists inhibit DNA fragmentation and toxic cell death induced by acetaminophen. FASEB J. 1993; 7(5): 453–463.
  29. Singh DK, Ahn B, Bohr VA. Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging. Biogerontology. 2009; 10(3): 235–252.
  30. Håkansson A, Zhivotovsky B, Orrenius S, et al. Apoptosis induced by a human milk protein. Proc Natl Acad Sci U S A. 1995; 92(17): 8064–8068.

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