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Chitosan Versus Dapagliflozin in a Diabetic Cardiomyopathy Mouse Model - PubMed

  • ️Mon Jan 01 2024

Chitosan Versus Dapagliflozin in a Diabetic Cardiomyopathy Mouse Model

Georgică Târtea et al. Int J Mol Sci. 2024.

Abstract

Diabetes mellitus is a metabolic disorder with global economic implications that can lead to complications such as diabetic cardiomyopathy. The aim of this study was to compare the effects of chitosan versus dapagliflozin in mouse diabetic cardiomyopathy. We used 32 C57Bl/6 male mice aged between 8 and 10 weeks, which were randomly divided into Control-without diabetes mellitus (DM), type 1 DM (T1DM), T1DM + Chitosan, and T1DM + Dapapgliflozin groups. We induced diabetes with streptozotocin and treated the animals for 12 weeks. The analysis showed a reduction in intramyocardial fibrosis in the T1DM + Dapapgliflozin compared to T1DM animals. In T1DM + CHIT, a reduction in intramyocardial fibrosis was observed although, accordingly, there was also no significant decrease in blood glucose. The level of oxidative stress was reduced in the groups of treated animals compared to T1DM. All these observed changes in the structure and function of hearts were highlighted in the echocardiographic examination. In the treated groups, there was delayed appearance of left ventricular (LV) hypertrophy, a slight decrease in the ejection fraction of the LV, and an improved diastolic profile. The results demonstrate that chitosan has promising effects on diabetic cardiomyopathy that are comparable to the beneficial effects of dapagliflozin.

Keywords: cardiomyopathy; chitosan; dapagliflozin; diabetes mellitus.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1

Assessment of the blood glucose levels as well as weight of animals before and after the administration of streptozotocin (STZ). Data are shown as mean ± S.D. (A) Plasma glucose concentration. (B) Weight of the animals at time of enrollment in the study. (C) Evolution of animal weight after onset of diabetes mellitus. The vertical dotted line represents the administration of STZ. α p < 0.05 vs. T1DM, * p < 0.05 vs. T1DM + Chitosan, # p < 0.05 vs. T1DM + Dapagliflozin, † p < 0.05 vs. T1DM, and ‡ < 0.05 vs. T1DM + Chitosan.

Figure 2
Figure 2

Effect of chitosan and dapagliflozin on total cholesterol (A) and triglycerides (B) after treatment for 12 weeks. Data are shown as mean ± S.D. α p < 0.05 vs. Control, * p < 0.05 vs. T1DM, # p < 0.05 vs. T1DM + Dapagliflozin, † p < 0.05 vs. T1DM, ‡ p < 0.05 vs. T1DM + Chitosan, and & p < 0.05 vs. T1DM + Dapagliflozin.

Figure 3
Figure 3

Representative images used for calculating the left ventricular ejection fraction (LVEJ) at the end of the study in mice without diabetes in the Control group (A), untreated mice in the T1DM group with diabetes (B), mice in the diabetic group treated with chitosan (T1MD + Chistosan) (C), and mice in the diabetic group treated with dapagliflozin (T1DM + Dapagliflozin) (D). The capital letters with (’) indicate the calculation of the end-diastolic volume of the left ventricle. The capital letters with (”) indicate the calculation of the end-systolic volume of the left ventricle as well as the automatic determination of LVEF.

Figure 4
Figure 4

Echocardiographic parameters evaluated in our study before administration of streptozotocin (week 8) and after administration of streptozotocin (weeks 12, 16, and 20). (A) Left ventricular ejection fraction (LVEF). (B) Fractional shortening (FS). (C) Left ventricle (LV) end-diastolic volume (LVEDV). (D) LV end-systolic volume (LVESV). (E) LV internal diastolic diameter (LVIDd). (F) LV internal systolic diameter (LVISd). (G) Interventricular septal width during end-diastole (IVSd). (H) LV posterior wall width during end-diastole (LVPWd). (I) E wave (early diastole). (J) A wave (atrial systole). (K) E/A ratio. (L) stroke volume (SV). α p < 0.05 vs. T1DM, * p < 0.05 vs. T1DM + Chitosan, # p < 0.05 vs. T1DM + Dapagliflozin, † p < 0.05 vs. T1DM + Chitosan, ‡ p < 0.05 vs. T1DM + Dapagliflozin, and & p < 0.05 vs. T1DM + Chitosan.

Figure 5
Figure 5

Representative images of M mode echocardiographic evaluation in mice without diabetes in the Control group (A), untreated mice in the T1DM group with diabetes (B), mice in the diabetic group treated with chitosan (T1MD + Chistosan) (C), and mice in the diabetic group treated with dapagliflozin (T1DM + Dapagliflozin) (D). E and A waves in mice without diabetes in the Control group (E), untreated mice in the T1DM group with diabetes (F), mice in the diabetic group treated with chitosan (T1MD + Chistosan) (G), and mice in the diabetic group treated with dapagliflozin (T1DM + Dapagliflozin) (H). The yellow arrows represent LV internal diastolic diameter (LVIDd), the green arrows represent LV internal systolic diameter (LVISd), the white solid lines represent interventricular septal width during end-diastole (IVSd), and the white dotted lines represent LV posterior wall width during end-diastole (VPWd).

Figure 6
Figure 6

Representative images of mice hearts from the group of Control animals without diabetes (A), the group of untreated animals with diabetes ((B)—T1DM), the group of animals with diabetes that were treated with chitosan ((C)—T1DM + Chitosan), and the group of animals with diabetes that were treated with dapagliflozin ((D)—T1DM + Dapagliflozin). Capital letters with ’ indicate representative images of fibrosis at the atrioventricular junction (blue arrows). Capital letters with ” indicate representative images of perivascular fibrosis (yellow arrows). Capital letters with ’’’ indicate representative images of intramural myocardial fibrosis (green arrows).

Figure 7
Figure 7

Effect of chitosan and dapagliflozin on cardiac fibrosis (mean ± S.E.M). (A) Fibrous tissue density at cardiac level (mm2 fibrous tissue/mm2 cardiac tissue). (B) Integrated optical density (IOD) reported per mm2 of cardiac tissue. (C) Perivascular fibrosis area. (D) Interstitial fibrosis area. † p < 0.05 vs. T1DM, ‡ p < 0.05 vs. T1DM + Chitosan, and & p < 0.05 vs. T1DM + Dapagliflozin, α p < 0.05 vs. Control, * p < 0.05 vs. T1DM + Chitosan, and # p < 0.05 vs. T1DM + Dapagliflozin.

Figure 8
Figure 8

Representative images of 4-hydroxynonenal (HNE) immunoexpression in mice without diabetes in the Control group (A), untreated mice in the T1DM group with diabetes (B), mice in the diabetic group treated with chitosan (T1MD + Chistosan) (C), and mice in the diabetic group treated with dapagliflozin (T1DM + Dapagliflozin) (D). (E) HNE immunoexpression (mean ± S.E.M.) analysis. α p < 0.05 vs. T1DM, * p < 0.05 vs. T1DM + Chitosan, # p < 0.05 vs. T1DM + Dapagliflozin, † p < 0.05 vs. T1DM + Chitosan, and ‡ p < 0.05 vs. T1DM + Dapagliflozin.

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Grants and funding

The Article Processing Charges were funded by the Doctoral School of the University of Medicine and Pharmacy of Craiova, Romania. This research was supported by internal grant no. 26/12C/13.07.2021.