Cardioprotective effect of concomitant administration of trigonelline and sitagliptin on cardiac biomarkers, lipid levels, electrocardiographic and heamodynamic modulation on cardiomyopathy in diabetic Wistar rats

Hemant V. Kamble, Subhash L. Bodhankar
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引用次数: 14

Abstract

Aim of the study

The present study was designed to investigate the possible association of concomitant administration of trigonelline (TRIG) and sitagliptin (SITA) on cardiomyopathy in diabetic rats.

Methods

Diabetes was induced in Wistar rats by administration of nicotinamide (NICO; 110 mg/kg) and streptozotocin (STZ; 65 mg/kg) intraperitonelly (i.p.). After confirmation of diabetes, rats were divided into following groups i.e. group 1: non-diabetic rats (ND); Group 2: diabetic rats (DC); Group 3: TRIG (50 mg/kg, p.o.); Group 4: SITA (5 mg/kg, p.o.); Group 5: TRIG + SITA (50 + 5 mg/kg, p.o.). Treatment with selected dose of TRIG and SITA was started from 3rd week after NICO–STZ injection and was continued up to 11th week. Cardiomyopathy was assessed by measuring serum glucose level, enzymatic cardiac markers, electrographic abnormalities, heamodynamic changes, lipid levels and histological examination of isolated heart tissue of treated animals.

Results

NICO–STZ diabetic rats showed extensive hyperglycemia, hyperlipidemia, and elevated levels of enzymatic cardiac markers compared to non-diabetic rats. Concomitant and monotherapy treatment of TRIG and SITA exhibited significant decrease in hyperglycemia as compared to diabetic rats. Whereas TRIG + SITA considerably reduced hyperlipidemia, alteration in levels enzymatic cardiac markers and improvement in cardiac function by improved electrographic abnormalities and heamodynamic changes. Overall, the findings revealed in this investigation demonstrated that concomitant administration of TRIG + SITA can be strong pharmacological therapy as compared to monotherapy used for the treatment of hyperglycemia, hyperlipidemia and cardiac dysfunctions in NICO–STZ-induced cardiomyopathy in Wistar rats.

Conclusion

We conclude that concomitant administration of TROG and SITA showed additive cardioprotective effect compared to monotherapy.

trigonelline和sitagliptin联用对糖尿病Wistar大鼠心脏生物标志物、血脂水平、心电图和血流动力学调节的心脏保护作用
本研究旨在探讨葫芦巴碱(TRIG)和西格列汀(sitagliptin)合用对糖尿病大鼠心肌病的影响。方法采用烟酰胺(NICO)诱导Wistar大鼠糖尿病;110 mg/kg)和链脲佐菌素(STZ;65 mg/kg)腹腔内(i.p.)。确诊为糖尿病后,将大鼠分为以下组:1组:非糖尿病大鼠(ND);第二组:糖尿病大鼠(DC);第三组:TRIG (50 mg/kg, p.o.);第4组:SITA (5 mg/kg, p.o.);第5组:TRIG + SITA (50 + 5 mg/kg, p.o.)。从NICO-STZ注射后第3周开始选择剂量的TRIG和SITA治疗,持续到第11周。心肌病的评估方法是测定治疗动物的血清葡萄糖水平、心肌酶标记物、电图异常、血流动力学变化、血脂水平和离体心脏组织的组织学检查。结果与非糖尿病大鼠相比,nico - stz糖尿病大鼠表现出广泛的高血糖、高脂血症和心肌酶标记物水平升高。与糖尿病大鼠相比,TRIG和SITA同时或单独治疗可显著降低高血糖。而TRIG + SITA通过改善电图异常和血流动力学改变,显著降低高脂血症、改变心脏酶标记物水平和改善心功能。总的来说,本研究的结果表明,与单一疗法相比,TRIG + SITA联合治疗nico - stz诱导的Wistar大鼠心肌病的高血糖、高脂血症和心功能障碍是一种强有力的药物疗法。结论与单药治疗相比,TROG和SITA合用具有增强的心脏保护作用。
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