Title (srp)

Efekti vitamina B6 i folne kiseline na kardiovaskularni sistem pacova sa dijabetes melitusom indukovanim streptozotocinom : doktorska disertacija

Author

Mutavdžin Krneta, Slavica, 1988-

Contributor

Đurić, Dragan, 1961-
Labudović Borović, Milica, 1971-
Milovanović, Branislav, 1962-
Gopčević, Kristina, 1960-
Jakovljević, Vladimir, 1971-

Description (srp)

Cilj: Istraživanje efekata subhronične primene vitamina B6 (piridoksina) i folne kiseline na kardiometaboličke parametre, parametre oksidativnog stresa, aktivnosti i distribuciju izoformi laktat i malat dehidrogenaze (LDH i MDH), remodelovanje srčanog tkiva procenom relativnih aktivnosti matriksnih metaloproteinaza (MMP) -2 i -9 u tkivu srca pacova, histomorfometrijske parametre srca, aorte i pankreasa i imunohistohemijske promene u tkivu srca i pankreasa kod pacova sa dijabetes melitusom (DM) indukovanim streptozotocinom (STZ).Materijal i metode: Istraživanje je sprovedeno tokom četiri nedelje. Eksperimentalne životinje su nasumično podeljene u 9 eksperimentalnih grupa (8 do 10 životinja/grupi): C1 (kontrolna grupa, fiziološki rastvor 1 ml/kg telesne mase (t.m.) intraperitonealno (i.p.) jednokratno); C2 (kontrolna grupa, fiziološki rastvor 1 ml/kg t.m. i.p. 28 dana); DM (STZ, 100 mg/kg t.m. u fiziološkom rastvoru i.p. jednokratno); P (piridoksin 7 mg/kg t.m. i.p. 28 dana), DM+P (STZ, 100 mg/kg t.m. i.p. jednokratno i piridoksin 7 mg/kg t.m. i.p. 28 dana); FA (folna kiselina 5 mg/kg t.m. i.p. 28 dana); DM+FA (STZ, 100 mg/kg t.m. i.p. jednokratno i folna kiselina 5 mg/kg t.m. i.p. 28 dana); P+FA (piridoksin 7 mg/kg t.m. i folna kiselina 5 mg/kg t.m. i.p. 28 dana); DM+P+FA (STZ, 100 mg/kg t.m. i.p. jednokratno i piridoksin 7 mg/kg t.m. i folna kiselina 5 mg/kg t.m. i.p. 28 dana). Određivani su različiti kardiometabolički biomarkeri u serumu i plazmi, a u tkivu srca aktivnosti antioksidativnih enzima [superoksid dismutaze (SOD) i katalaze (CAT)], aktivnosti i distribucija izoformi LDH i MDH, relativne aktivnosti MMP-2 i MMP-9. Pored toga, tkivo srca, aorte i pankreasa korišćeno je za analizu histomorfometrijskih parametara. Imunohistohemijska analiza rađena je na tkivu srca (BCL-2, BCL-6, Ki-67, PCNA) i tkivu pankreasa (insulin).Rezultati: Primena STZ je bila praćena značajnim smanjenjem telesne mase, porastom koncentracije glukoze i smanjenjem nivoa insulina u serumu, kao i povećanjem HOMA-IR, smanjenjem koncentracije troponina T i fibrinogena, povećanjem aktivnosti fon Vilebrandovog faktora, aktivnosti hepatičnih enzima: aspartat aminotransferaze (AST), alanin aminotransferaze (ALT) i alkalne fosfataze (ALP), kao i -amilaze (-AMY), i smanjenjem koncentracije ukupnih proteina i albumina u serumu. Koncentracija uree u serumu je bila povišena, a kreatinina snižena nakon primene STZ. U homogenatu srčanog tkiva pokazano je povećanje SOD, CAT i MDH. Detektovane su četiri LDH izoforme (LDH-1, LDH-2, LDH-3 i LDH-4) i tri MDH izoforme [peroksizomalna (pMDH), mitohondrijalna (mMDH) i citosolna (cMDH)] kod svih eksperimentalnih životinja. Primena STZ je bila praćena smanjenjem aktivnosti LDH-1 i povećanjem aktivnosti LDH-3 i LDH-4, kao i smanjenjem aktivnosti cMDH i povećanjem aktivnosti pMDH. U DM grupi je bila smanjena aktivnost aktivnog oblika MMP-9 (aMMP-9) i povećana aktivnost latentnog oblika MMP-2 (proMMP-2) u poređenju sa C1 grupom, pored toga u DM grupi se uočava i aktivni oblik MMP-2 (aMMP-2). Nakon primene STZ uočeno je smanjenje debljine interventrikularnog septuma (IVS). Primena STZ i DM su smanjili broj Langerhansovih ostrvaca po mm2 površine tkiva pankreasa, kao i broj insulin pozitivnih Langerhansovih ostrvaca. Nije bilo BCL-2 i BCL-6 pozitivnih ćelija, ni razlika u pozitivnosti Ki-67, dok je pozitivnost PCNA bila statistički značajno manja u zidu leve i desne komore i IVS pacova sa DM. Primena piridoksina kod pacova sa DM je dovela do smanjenja aktivnosti enzima jetre (AST, ALT i ALP), -AMY, CAT i MDH. Bila je praćena povećanjem aktivnosti LDH-1 i smanjenjem aktivnosti LDH-3 i LDH-4, smanjenjem pMDH i povećanjem mMDH aktivnosti, kao i povećanjem aktivnosti aMMP-2 i aMMP-9. Primena folne kiseline kod pacova sa DM je značajno smanjila koncentraciju glukoze i aktivnost ALP, povećala je koncentraciju fibrinogena, uree i kreatinina. Dovela je do smanjenja aktivnosti CAT, SOD i MDH. Povećala je aktivnosti LDH-1 i LDH-2 i smanjila aktivnosti LDH-3 i LDH-4, i pMDH...

Description (srp)

Medicina - Fiziološke nauke / Medicine - Physiological sciences Datum odbrane: 19.09.2022.

Description (eng)

Objective: Investigation of the effects of subchronic application of vitamin B6 (pyridoxine) and folic acid on cardiometabolic and oxidative stress parameters, activities and distribution of lactate and malate dehydrogenase (LDH and MDH) isoforms, cardiac tissue remodeling by estimating the relative activities of matrix metalloproteinase (MMP) -2 and -9, histomorphometric parameters of the heart, aorta and pancreas, and immunohistochemical changes in heart and pancreatic tissue in rats with streptozotocin-induced diabetes mellitus (DM).Materials and methods: The study was conducted for four weeks. Experimental animals were divided into 9 experimental groups randomly (8 to 10 animals/group): C1 (control group, saline 1 ml/kg body weight (b.w) intraperitoneally (i.p.) one day); C2 (control group, saline 1 ml/kg b.w. i.p. 28 days); DM (STZ, 100 mg/kg b.w. in saline i.p. one day); P (pyridoxine 7 mg/kg b.w. i.p. 28 days), DM+P (STZ, 100 mg/kg b.w. i.p. one day and pyridoxine 7 mg/kg b.w. i.p. 28 days); FA (folic acid 5 mg/kg b.w. i.p. 28 days); DM+FA (STZ, 100 mg/kg b.w. i.p. one day and folic acid 5 mg/kg b.w. i.p. 28 days); P+FA (pyridoxine 7 mg/kg b.w. i.p. and folic acid 5 mg/kg b.w. i.p. 28 days); DM+P+FA (STZ, 100 mg/kg b.w. i.p. one day and pyridoxine 7 mg/kg b.w. i.p. and folic acid 5 mg/kg b.w. i.p. 28 days). Cardiometabolic biomarkers were determined in serum and plasma, and activities of antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], activities and distribution of LDH and MDH isoforms, relative activities of MMP-2 and MMP-9 were determined in the heart tissue. Tissue of the heart, aorta and pancreas was used for histomorphometric analysis. Immunohistochemical analysis was performed on heart tissue (BCL-2, BCL-6, Ki-67, PCNA) and pancreatic tissue (insulin).Results: After STZ application the following changes were observed: significant decrease in body weight, increase in glucose concentration and decrease in serum insulin level, as well as increase in HOMA-IR, decrease in troponin T and fibrinogen, increase in von Willebrand factor activity, activity of hepatic enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), as well as -amylase (-AMI), and decreased concentration of total proteins and albumin in serum. Serum urea was elevated and creatinine decreased after STZ administration. An increase in SOD, CAT and MDH was shown in the homogenate of cardiac tissue. Four LDH isoforms (LDH-1, LDH-2, LDH-3 and LDH-4) and three MDH isoforms [peroxisomal (pMDH), mitochondrial (mMDH) and cytosolic (cMDH)] were detected in all experimental animals. The application of STZ was followed by a decrease in LDH-1 activity and an increase in LDH-3 and LDH-4 activity, as well as a decrease in cMDH activity and an increase in pMDH activity. In the DM group, the activity of the active form MMP-9 (aMMP-9) was reduced and the activity of the latent form MMP-2 (proMMP-2) was increased in comparison to the C1 group, in addition, the active form MMP-2 (aMMP-2) was observed in the DM group. After the application of STZ, a decrease in the thickness of the interventricular septum (IVS) was observed. The use of STZ and DM reduced the number of islets of Langerhans per mm2 of pancreatic tissue surface area, as well as the number of insulin-positive islets of Langerhans. There were no BCL-2 and BCL-6 positive cells and no difference in Ki-67 positivity was detected, while PCNA positivity was statistically significantly lower in left and right ventricular wall and IVS of rats with DM. Administration of pyridoxine in rats with DM resulted in decreased liver enzyme activity (AST, ALT, and ALP), -AMY, CAT, and MDH. There was an increase in LDH-1 activity and a decrease in LDH-3 and LDH-4 activity, a decrease in pMDH and an increase in mMDH activity, as well as an increase in aMMP-2 and aMMP-9 activity. Folic acid administration in rats with DM significantly reduced the concentration of glucose and ALP activity, increased the concentration of fibrinogen, urea and creatinine. It led to a reduction in the activities of CAT, SOD and MDH. Folic acid increased the activities of LDH-1 and LDH-2 and decreased the activities of LDH-3 and LDH-4, and pMDH...

Object languages

Serbian

Date

2022

Rights

Creative Commons License
This work is licensed under a
CC BY-ND 3.0 AT - Creative Commons Attribution-NoDerivs 3.0 Austria License.

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Subject

OSNO - Opšta sistematizacija naučnih oblasti, Fiziologija

diabetes mellitus, streptozotocin, pyridoxine, folic acid, biochemical markers, oxidative stress, cardiac tissue remodeling, immunohistochemical markers, rat

Identifiers