Begum Mst Marium, Sultana Zakia, Ershad Ali Md, Jami Md Safkath Ibne, Khondkar Proma, Khan Md Masuduzzaman, Haque Md Mominul
Department of Pharmacy, University of Rajshahi, Rajshahi, 6205 Bangladesh.
Department of Chemistry, Dhaka College, Dhaka, 1000 Bangladesh.
Indian J Clin Biochem. 2014 Oct;29(4):452-61. doi: 10.1007/s12291-013-0393-1. Epub 2013 Oct 24.
High blood glucose level, elevated level of liver enzyme, necrosis and shrinkage of islets of Langerhans has been implicated in the pathogenesis of type 2 diabetes. High blood glucose cause oxidative stress, production of free radical as well as elevated SGPT and SGOT level. Both glibenclamide and simvastatin in fixed dose used as antihyperglycemic antidyslipidemic and antioxidative agents for type 2 diabetes treatment. This study therefore aimed to evaluate the antihyperglycemic, antidyslipidemic and antioxidative effect of fixed dose combination of glibenclamide (0.6 mg/70 kg body weight) and simvastatin (5 mg/70 kg body weight) on long term alloxan induced diabetic rats with cardiovascular disease using various diagnostic kits as a parameter of phamacotherapeutic and pharmacological effect. The study was carried out using 96 Swiss Albino male rats weighing about 200-220 g. Combination therapy induced a significant decrease in blood glucose level in alloxan induced diabetic rats, from 33.75 ± 1.65 to 5.80 ± 0.07 mmol/l 2 h after last dose administration, after 4 weeks treatment. In case of dyslipidemic effect, combination therapy reduced total cholesterol (45 %), triglyceride (36 %) and low density lipoprotein-cholesterol (32 %) levels significantly and increased high density lipoprotein-cholesterol level (57 %) in comparison with their respective diabetic control groups. Results of this study showed that combination therapy effectively decreased SGPT (ALAT) (55 %) and SGOT (ASAT) (51 %) in comparison with diabetic control group. It was also observed that catalase and superoxide dismutase enzyme activity was increased by 58 and 91 % respectively in comparison with diabetic control group after 4 weeks treatment with combination of both drugs. In conclusion, these findings of combination therapy (glibenclamide and simvastatin) on alloxan induced diabetes in rats are significantly better than monotherapy using single drug. The results of the present study suggest that, combination of the fixed dose of glibenclamide and simvastatin might be efficacious in patients with diabetic dyslipidemia and increased oxidative stress. Furthermore, this combination therapy offer dosage convenience to the patients and by virtue of its dual mode of action might be a useful addition to the therapeutic armamentarium for patients with diabetic dyslipidemia and oxidative stress.
高血糖水平、肝酶水平升高、胰岛的坏死和萎缩与2型糖尿病的发病机制有关。高血糖会导致氧化应激、自由基产生以及血清谷丙转氨酶（SGPT）和血清谷草转氨酶（SGOT）水平升高。格列本脲和辛伐他汀固定剂量联合使用，作为抗高血糖、抗血脂异常和抗氧化剂用于2型糖尿病的治疗。因此，本研究旨在使用各种诊断试剂盒作为药物治疗和药理作用的参数，评估格列本脲（0.6毫克/70千克体重）和辛伐他汀（5毫克/70千克体重）固定剂量组合对长期用四氧嘧啶诱导的患有心血管疾病的糖尿病大鼠的抗高血糖、抗血脂异常和抗氧化作用。该研究使用了96只体重约200 - 220克的瑞士白化雄性大鼠。联合治疗使四氧嘧啶诱导的糖尿病大鼠的血糖水平显著降低，在末次给药后2小时，经过4周治疗，血糖水平从33.75±1.65降至5.80±0.07毫摩尔/升。在血脂异常作用方面，与各自的糖尿病对照组相比，联合治疗显著降低了总胆固醇（45%）、甘油三酯（36%）和低密度脂蛋白胆固醇（32%）水平，并提高了高密度脂蛋白胆固醇水平（57%）。本研究结果表明，与糖尿病对照组相比，联合治疗有效降低了SGPT（丙氨酸转氨酶，ALAT）（55%）和SGOT（天冬氨酸转氨酶，ASAT）（51%）。还观察到，在用两种药物联合治疗4周后，与糖尿病对照组相比，过氧化氢酶和超氧化物歧化酶的活性分别提高了58%和91%。总之，联合治疗（格列本脲和辛伐他汀）对大鼠四氧嘧啶诱导的糖尿病的这些发现明显优于单药单一疗法。本研究结果表明，固定剂量的格列本脲和辛伐他汀联合使用可能对糖尿病血脂异常和氧化应激增加的患者有效。此外，这种联合治疗为患者提供了用药便利性，并且凭借其双重作用模式，可能是糖尿病血脂异常和氧化应激患者治疗药物库中的一个有用补充。
