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Pak J Pharm Sci ; 34(5(Supplementary)): 1939-1944, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34836863

RESUMO

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.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/toxicidade , Hipoglicemiantes/toxicidade , Mutagênicos/toxicidade , Sinvastatina/toxicidade , Fosfato de Sitagliptina/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Chlorocebus aethiops , Ensaio Cometa , Dano ao DNA , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Interações Medicamentosas , Sinergismo Farmacológico , Células Vero
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