Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University (LCWU), Lahore, Pakistan.
Pak J Pharm Sci. 2021 Sep;34(5(Supplementary)):1939-1944.
Type 2 Diabetes Mellitus (T2DM) patients are at high risk of Coronary Heart Disease (CHD) and need a global therapeutic intervention. A fixed-dose combination prescription medication containing anti-diabetic drug (Sitagliptin) and lipid lowering (Simvastatin) has recently been approved. Present study was designed to explore the potential synergistic toxic effects of sitagliptin and simvastatin at cellular level. MTT assay revealed the potential synergistic cytotoxic effect whereas Comet assay spotlighted the genotoxicity. MTT assay conducted on Vero cell lines revealed no significant change in proliferative activity upon treatment with simvastatin but cell survival percentage (CSP) decreased upon treatment with sitagliptin (51% at 1000μg/mL). However, combination of both drugs exhibited a better survival percentage except highest dose combination (1000:500μg/mL) which augmented antiproliferative effects rendering CSP 71.6%. The genotoxic assay spotted that Simvastatin produced less damage to DNA with the threshold of 500μg/ml whereas Sitagliptin significantly damage above the 250μg/mL, However, combination of drugs produced lesser damage than Sitagliptin alone. The findings concluded a non-genotoxic combination of sitagliptin and simvastatin which possess a least cytotoxic potential suggesting the safe use of the combination both in T2DM and CHD.
2 型糖尿病（T2DM）患者患冠心病（CHD）的风险很高，需要进行全球治疗干预。最近批准了一种含有抗糖尿病药物（西他列汀）和降脂药物（辛伐他汀）的固定剂量组合处方药物。本研究旨在探索西他列汀和辛伐他汀在细胞水平上的潜在协同毒性作用。MTT 测定法显示出潜在的协同细胞毒性作用，而彗星试验则突出了遗传毒性。在 Vero 细胞系上进行的 MTT 测定法表明，辛伐他汀处理后增殖活性没有明显变化，但西他列汀处理后细胞存活率（CSP）下降（1000μg/mL 时为 51%）。然而，两种药物的联合使用表现出更好的存活率，除了最高剂量组合（1000:500μg/mL）外，该组合增强了抗增殖作用，使 CSP 达到 71.6%。遗传毒性试验发现，辛伐他汀在 500μg/ml 的阈值下对 DNA 的损伤较小，而西他列汀在 250μg/ml 以上时则会显著损伤 DNA，然而，联合使用药物比单独使用西他列汀产生的损伤更小。研究结果得出结论，西他列汀和辛伐他汀的联合使用具有非遗传毒性，且细胞毒性最小，这表明该组合在 2 型糖尿病和冠心病患者中的安全使用。
