The study evaluating the effect of empagliflozin and dapagliflozin on miR-133a expression and oxidative stress in the rat heart induced by streptozotocin/nicotinamide

Abstract

Empagliflozin and dapagliflozin exert their effects by inhibiting sodium glucose cotransporter 2 (SGLT2), which inhibits glucose absorption from renal tubules. This class of drugs has also been demonstrated in studies to be protective against cardiovascular complications associated with type 2 diabetes mellitus (T2DM). Even in cases without T2DM, they have clinical utility due to their cardioprotective effects. The effects of empagliflozin and dapagliflozin on cardiovascular disorders remain incompletely understood. MicroRNAs (miRNAs) represent a class of small, non-coding RNA molecules that have been implicated in the pathogenesis of cardiovascular damage. miRNA expressions increase or decrease due to hyperglycemia and oxidative stress that occur in T2DM. This study intended to explore the SGLT2 inhibitor effects on miR-133a expressions in diabetic heart tissue by establishing a streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rat model. Also, antioxidant activities were investigated in the heart and aorta tissue. Male-female Sprague-Dawley rats were injected with NA (100 mg/kg) and STZ (55 mg/kg) intraperitoneally (i.p.) respectively. One week after induction T2DM, treatments were carried out for four weeks. At the and of the treatment, the heart and thoracic aortic tissues of rats were removed. In the heart tissue glutathione (GSH), lipid peroxides (LPO), and myeloperoxidase (MPO) levels, and in the aorta tissue GSH and LPO levels were determined by fluorences method. miR-133a expression changes were assessed in the heart tissue by RT-PCR analyses. According to our results, dapagliflozin showed an antioxidant effect by increasing GSH levels in the heart (p<0.01) and aorta tissue more than empagliflozin. miR-133a expressions increased in the T2DM group and decreased in the EMPA (p<0.05) and DAPA groups (p<0.01). Studies on miR-133a expressions in different diabetes models are needed.

Keywords

• Type 2 Diabetes Mellitus
• miR-133a
• oxidative stress
• cardiovascular complications
• rat

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