PMID- 34836863
OWN - NLM
STAT- MEDLINE
DCOM- 20220225
LR  - 20220225
IS  - 1011-601X (Print)
IS  - 1011-601X (Linking)
VI  - 34
IP  - 5(Supplementary)
DP  - 2021 Sep
TI  - Genotoxic and cytotoxic assessment of sitagliptin and simvastatin alone and in 
      combination.
PG  - 1939-1944
AB  - 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 1000mug/mL). However, 
      combination of both drugs exhibited a better survival percentage except highest 
      dose combination (1000:500mug/mL) which augmented antiproliferative effects 
      rendering CSP 71.6%. The genotoxic assay spotted that Simvastatin produced less 
      damage to DNA with the threshold of 500mug/ml whereas Sitagliptin significantly 
      damage above the 250mug/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.
FAU - Majeed Khan, Humaira
AU  - Majeed Khan H
AD  - Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, 
      Lahore College for Women University (LCWU), Lahore, Pakistan.
FAU - Nawaz, Huma
AU  - Nawaz H
AD  - Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, 
      Lahore College for Women University (LCWU), Lahore, Pakistan.
FAU - Aerooj, Huma
AU  - Aerooj H
AD  - Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, 
      Lahore College for Women University (LCWU), Lahore, Pakistan.
FAU - Sharif, Ali
AU  - Sharif A
AD  - Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, 
      Lahore College for Women University (LCWU), Lahore, Pakistan.
LA  - eng
PT  - Journal Article
PL  - Pakistan
TA  - Pak J Pharm Sci
JT  - Pakistan journal of pharmaceutical sciences
JID - 9426356
RN  - 0 (Drug Combinations)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Mutagens)
RN  - AGG2FN16EV (Simvastatin)
RN  - TS63EW8X6F (Sitagliptin Phosphate)
SB  - IM
MH  - Animals
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/*drug effects
MH  - Chlorocebus aethiops
MH  - Comet Assay
MH  - DNA Damage
MH  - Diabetes Mellitus, Type 2/drug therapy
MH  - Drug Combinations
MH  - Drug Interactions
MH  - Drug Synergism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*toxicity
MH  - Hypoglycemic Agents/*toxicity
MH  - Mutagens/*toxicity
MH  - Simvastatin/*toxicity
MH  - Sitagliptin Phosphate/*toxicity
MH  - Vero Cells
EDAT- 2021/11/28 06:00
MHDA- 2022/02/26 06:00
CRDT- 2021/11/27 05:33
PHST- 2021/11/27 05:33 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2022/02/26 06:00 [medline]
PST - ppublish
SO  - Pak J Pharm Sci. 2021 Sep;34(5(Supplementary)):1939-1944.