Page 24 - JCTR-10-4

Journal of Clinical and Translational Research 2024; 10(4): 246-255

Journal of Clinical and Translational Research

Journal homepage: http://www.jctres.com/en/home

ORIGINAL ARTICLE

Potential cardioprotective effect of Vitamin D and sodium-glucose

transport protein 2 inhibitor in improving cardiac hypertrophy and

fibrosis in Type 2 diabetic rats

Nyoman Ririn Chandrika Sari *, Prayoga Setiawan , I. Nyoman Wiryawan , Anak Agung Ayu Dwi Adelia Yasmin ,
1
1
1
1
I. Gusti Kamasan Nyoman Arijana 2
1 Department of Cardiology and Vascular Medicine, Faculty of Medicine Udayana University/Prof. I.G.N.G Ngoerah General Hospital, Bali,
Indonesia, Department of Histology, Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia
2
ARTICLE INFO ABSTRACT

Article history: Background: Diabetes mellitus (DM) is a major risk factor for cardiovascular diseases.
Received: March 3, 2024 The progression of myocardial abnormalities due to DM occurs slowly but is progressive and
Accepted: July 26, 2024 asymptomatic. Sodium-glucose transport protein 2 inhibitors (SGLT-2i) and Vitamin D have
Published Online: August 23, 2024 potential cardioprotective properties that inhibit cardiomyocyte fibrosis and hypertrophy, which
are early structural changes that occur in the heart of DM patients.
Keywords: Aim: The study aimed to determine the potential protective effects of SGLT-2i and Vitamin D
Cardiac hypertrophy administration on cardiac hypertrophy and fibrosis in Type 2 diabetic rats.
Cardiac fibrosis Methods: This is an experimental study with a post-test-only control group design. Thirty-two
Type 2 diabetes male Wistar rats were given a high-fat/high-glucose (HF/HG) diet. After 3 weeks, rats were given
Diabetic rats an injection of streptozotocin (STZ 35 mg/kg) to induce pancreatic damage. The diabetic rats
Collagen deposition were then divided into four groups (n = 8 per group): untreated diabetic group (HF/HG/STZ),
Cardiomyocyte cross-sectional area the diabetic group treated with empagliflozin (EMPA) 10 mg/kg body weight (BW) (HF/HG/
β-myosin heavy chain STZ+EMPA), the diabetic group treated with Vitamin D 225 IU/day (HF/HG/STZ+VitD), and the
Transforming growth factor-β diabetic group treated with a combination of EMPA 10 mg/kg BW and Vitamin D 225 IU/day (HF/
HG/STZ+EMPA+VitD). Treatments were given by oral gavage for 8 weeks. Left ventricular biopsy
*Corresponding author: was performed at week 13 to examine collagen deposition, the cardiomyocyte cross-sectional area
Nyoman Ririn Chandrika Sari (CSA), and the mRNA expression of β-myosin heavy chain (β-MHC) and transforming growth
Department of Cardiology and Vascular factor-β (TGF-β). All the obtained data were analyzed statistically.
Medicine, Faculty of Medicine, Udayana Results: The administration of EMPA, Vitamin D, and combination therapy of EMPA and Vitamin
University, Denpasar, Bali, Indonesia D reduced the mRNA expression of β-MHC and TGF-β in diabetic rats compared to the untreated
Email: ririnchandrika@gmail.com diabetic group. The administration of EMPA, Vitamin D, and combination therapy also resulted in
a decrease in both the cardiomyocyte CSA and collagen deposition. Compared to monotherapy,
© 2024 Author(s). This is an Open- combination therapy led to significantly better parameter reduction.
Access article distributed under the terms Conclusion: Administration of EMPA, Vitamin D, and combination therapy improved cardiac
of the Creative Commons Attribution- hypertrophy and fibrosis in type 2 diabetic rats.
Noncommercial License, permitting all
non-commercial use, distribution, and Relevance for Patients: The combination of Vitamin D and SGLT-2i may be proposed as a
reproduction in any medium, provided the cardioprotective strategy and preventive measure to reduce the incidence of cardiovascular disease
original work is properly cited. in patients with Type 2 DM.

1. Introduction

Cardiovascular disease is the leading cause of death worldwide, and diabetes mellitus
(DM) is known to be a major risk factor for the progression of cardiovascular diseases [1].
According to the Framingham Heart Study, men and women with DM have a higher risk

DOI: http://doi.org/10.36922/jctr.24.00010