Naslov (srp)

Efekti vitamina B6, folne kiseline i dozirane fizičke aktivnosti na biohemijske i histomorfološke promene kardiovaskularnog i digestivnog sistema pacova, uzrokovane subhroničnom hiperhomocisteinemijom : doktorska disertacija

Autor

Todorović, Dušan, 1991-

Doprinosi

Jakovljević, Vladimir, 1971-
Stanković, Sanja, 1969-
Stojanović, Marija, 1985-
Đurić, Dragan, 1961-
Gopčević, Kristina, 1960-
Kojić, Zvezdana, 1965-
Labudović Borović, Milica, 1971-

Opis (srp)

Cilj: Istraživanje efekata dvonedeljne primene homocisteina (Hcy) i četvoronedeljne primene vitamina B6, folne kiseline (FK) i dozirane fizičke aktivnosti u uslovima hiperhomocisteinemije (HHcy) na biohemijske biomarkere u serumu i plazmi, parametre oksidativnog stresa, aktivnosti metaboličkih enzima, aktivnosti matriks metaloproteinaza (MMP), kao i histološke i histomorfometrijske promene srca, aorte, jetre i kolona.Materijal i metode: Eksperimentalni protokol je izveden u toku 28 uzastopnih dana. Mužjaci pacova soja Wistar albino su randomizovano podeljeni u 12 grupa (10 pacova u svakoj grupi): kontrolna grupa K-14: aplikacija fiziološkog rastvora (fiziološki rastvor 0,9% NaCl (f.r.) 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana; eksperimentalna grupa H-14: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana; kontrolna grupa K-28: aplikacija fiziološkog rastvora (f.r. 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i fiziološkog rastvora (f.r. 0,5 mL i.p.) jedan put dnevno, 28 dana; eksperimentalna grupa H-28: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i fiziološkog rastvora (f.r. 0,5 mL i.p.) jedan put dnevno, 28 dana; kontrolna grupa K-B6: aplikacija fiziološkog rastvora (f.r. 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i vitamina B6 (7 mg/kg tm. i.p.) jedan put dnevno, 28 dana; eksperimentalna grupa H-B6: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i vitamina B6 (7 mg/kg tm. i.p.) jedan put dnevno, 28 dana; kontrolna grupa K-FK: aplikacija fiziološkog rastvora (f.r. 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i FK (5 mg/kg tm. i.p.) jedan put dnevno, 28 dana; eksperimentalna grupa H-FK: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i FK (5 mg/kg tm. i.p.) jedan put dnevno, 28 dana; kontrolna grupa K-B6+FK: aplikacija fiziološkog rastvora (f.r. 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i vitamina B6 (7 mg/kg tm. i.p.) i FK (5 mg/kg tm. i.p.) jednom dnevno, 28 dana; eksperimentalna grupa H-B6+FK: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i vitamina B6 (7 mg/kg tm. i.p.) i FK (5 mg/kg tm. i.p.) jednom dnevno, 28 dana; kontrolna grupa K-FA: aplikacija fiziološkog rastvora (f.r. 0,2 mL s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i tretman aerobnom fizičkom aktivnošću (30 min/dan, brzina trake 20 m/min, nagib trake 0°), 28 dana; eksperimentalna grupa H-FA: aplikacija Hcy (0,45 μmol/g tm. s.c.) dva puta na dan u razmaku od 8 sati, 14 dana i tretman aerobnom fizičkom aktivnošću (30 min/dan, brzina trake 20 m/min, nagib trake 0°), 28 dana. Određivani su kardiovaskularni biomarkeri u serumu: koncentracija Hcy, ukupnog holesterola, lipoproteina velike gustine (HDL), lipoproteina male gustine (LDL), trigilicerida, aktivnost laktat dehidrogenaze (LDH), koncentracija visoko senzitivnog troponina T, vitamina B12 i folata; hemostatski biomarkeri u plazmi: koncentracija fibrinogena, D-dimera i von Wilebrandovog faktora (vWF); kao i hapato-renalno-pankreatični biomarkeri u serumu: koncentracija glukoze, ukupnih proteina, albumina, aktivnost aspartat aminotransferaze (AST), aktivnost alanin aminotransferaze (ALT), koncentracija uree, kreatinina, mokraćne kiseline, aktivnost amilaze i koncentracija C reaktivnog proteina. U tkivu srca, jetre i kolona određivani su parametri oksidativnog stresa: aktivnost katalaze (CAT), superoksid dismutaze (SOD) - ukupna aktivnost i distribucija izoformi, koncentracija malondialdehida (MDA), aktivnosti i distribucija izoformi LDH i malat dehidrogenaze (MDH), relativne aktivnosti MMP izoformi: MMP-2 i MMP-9. Pored toga, tkivo srca, aorte, jetre i kolona korišćeno je za histološku analizu.Rezultati: Aplikacija Hcy dovela je do razvoja HHcy, porasta serumske koncentracije LDL, vitamina B12, glukoze, ukupnih proteina, albumina i kreatinina i serumske aktivnosti AST, porasta ukupne aktivnosti SOD i koncentracije MDA, izazvala je porast debljine zida leve komore i debljine zida desne komore, dovela do porasta debljine tunike medije aorte i do porasta aktivnosti MMP-9 u jetri, dovela do smanjenja ukupne aktivnost SOD u kolonu i porasta dubine Liberkinovih kripti, debljine tunike mukoze i broja ćelija u lamini propriji kolona...

Opis (srp)

Medicina - Fiziološke nauke / Medicine- Physiological sciences Datum odbrane: 28.02.2024.

Opis (eng)

Objective: Examination of the effects of a two-week application of homocysteine (Hcy) and a four-week application of vitamins B6, folic acid (FK) and dosed physical activity under conditions of hyperhomocysteinemia (HHcy) on biochemical biomarkers in serum and plasma, parameters of oxidative stress, activities of metabolic enzymes, activities of matrix metalloproteinases (MMP), as well as histological and histomorphometric changes in the heart, aorta, liver, and colon.Materials and methods: Experimental protocol was conducted during 28 consecutive days. Male Wistar albino rats were randomly divided into 12 groups (10 rats in each group): control group K-14: administration of saline (physiological solution 0.9% NaCl (p.s.) 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days; experimental group H-14: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days; control group K-28: administration of physiological saline (0.9% p.s. 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days, and physiological saline (p.s. 0.5 mL i.p.) once daily for 28 days; experimental group H-28: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days, and physiological saline (p.s. 0.5 mL i.p.) once daily for 28 days; control group K-B6: administration of physiological saline (p.s. 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days, and vitamin B6 (7 mg/kg b.w. i.p.) once daily for 28 days; experimental group H-B6: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days and vitamin B6 (7 mg/kg b.w. i.p.) once daily for 28 days; control group K-FK: administration of physiological saline (p.s. 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days, and FK (5 mg/kg b.w. i.p.) once daily for 28 days; experimental group H-FK: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days, and FK (5 mg/kg b.w. i.p.) once daily for 28 days; control group K-B6+FK: administration of physiological saline (p.s. 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days, and vitamin B6 (7 mg/kg b.w. i.p.) and FK (5 mg/kg b.w. i.p.) once daily for 28 days; experimental group H-B6+FK: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days, and vitamin B6 (7 mg/kg b.w. i.p.) and FK (5 mg/kg b.w. i.p.) once daily for 28 days; control group K-FA: administration of physiological saline (p.s. 0.2 mL s.c.) twice daily at 8-hour intervals for 14 days, and aerobic physical activity treatment (30 min/day, speed 20 m/min, inclination 0°) for 28 days; experimental group H-FA: administration of Hcy (0.45 μmol/g b.w. s.c.) twice daily at 8-hour intervals for 14 days, and aerobic physical activity treatment (30 min/day, speed 20 m/min, inclination 0°) for 28 days. Cardiovascular biomarkers in serum were determined: concentrations of homocysteine (Hcy), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, activity of lactate dehydrogenase (LDH), concentrations of high-sensitive troponin T, vitamin B12, and folates; hemostatic biomarkers in plasma: concentrations of fibrinogen, D-dimer, and von Willebrand factor (vWF); as well as hepato-renal-pancreatic biomarkers in serum: concentrations of glucose, total proteins, albumin, activity of aspartate aminotransferase (AST), activity of alanine aminotransferase (ALT), concentrations of urea, creatinine, uric acid, activity of amylase, and concentrations of C-reactive protein. In the tissues of the heart, liver, and colon, parameters of oxidative stress were determined: activity of catalase (CAT), superoxide dismutase (SOD) - total activity and isoform distribution, concentrations of malondialdehyde (MDA), activities and isoform distribution of LDH and malate dehydrogenase (MDH), relative activities of MMP isoforms: MMP-2 and MMP-9. In addition, tissues of the heart, aorta, liver, and colon were used for histological analysis.Results: The application of Hcy led to the development of HHcy, an increase in the serum concentration of LDL, vitamin B12, glucose, total protein, albumin, and creatinine, as well as an elevation in the serum activity of AST. Additionally, it resulted in an increase in the total activity of SOD and MDA concentration, an increase in the left ventricular wall thickness and the right ventricular wall thickness, caused an elevation in the aortic tunica media thickness, and led to an upsurge in the MMP-9 activity in the liver. It also resulted in a reduction in the total SOD activity in the colon, an increase in the depth of crypts of Lieberkuhn, mucosal tunica thickness, and the number of cells in the lamina propria of the colon...

Jezik

srpski

Datum

2023

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-ND 3.0 AT - Creative Commons Autorstvo - Bez prerada Austria License.

http://creativecommons.org/licenses/by-nd/3.0/at/legalcode

Predmet

OSNO - Opšta sistematizacija naučnih oblasti, Fiziologija

cardiac metabolism, cardiovascular system, digestive system, folic acid, homocysteine, hyperhomocysteinemia, oxidative stress, physical activity, rat, vitamin B6

OSNO - Opšta sistematizacija naučnih oblasti, Fiziologija

digestivni sistem, fizička aktivnost, folna kiselina, hiperhomocisteinemija, homocistein, kardiovaskularni sistem, metabolizam srca, oksidativni stres, pacov, vitamin B6

612.015.3(043.3)