Open AccessA toxicology study to evaluate the embryotoxicity of metformin compared with the hypoglycemic drugs, the anticancer drug, the anti‐epileptic drug, the antibiotic, and the cyclo‐oxygenase (COX)‐2 inhibitor
Author(s) -
Li Li,
Zhang Xing,
Wang Lei,
Chai Zhenhai,
Shen Xiuping,
Zhang Zongpeng,
Liu Changxiao
Publication year - 2015
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12251
Subject(s) - metformin , pharmacology , medicine , drug , embryonic stem cell , developmental toxicity , antibiotics , diabetes mellitus , biology , endocrinology , biochemistry , gestation , pregnancy , genetics , gene
Background The safe use of medications in pregnant females, their embryos and in offspring is important. The aim of the present study was to evaluate embryotoxicity of metformin ( MET ) compared with other hypoglycemic drugs (rosiglitazone [ RSG ] and glimepiride [ GLIM ]), the anticancer drug 5‐fluorouracil (5‐ FU ), the anti‐epileptic drug diphenylhydantoin ( DPH ), the antibiotic penicillin G ( P en G ), and the cyclo‐oxygenase ( COX )‐2 inhibitor nimesulide ( NIM ) in an embryonic stem cell test ( EST ). Methods Differences in the expression of developmental marker genes following treatment with the test compounds during the course of differentiation (from embryonic stem cell D 3 ( D 3 cells) to myocardial cells) were determined using real‐time quantitative polymerase chain reaction. In these studies, 5‐ FU was used as a positive control and P en G was used as a negative control. The cytotoxicity of these drugs against D 3 cells and 3 T 3 fibroblasts was determined by the 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2 H ‐tetrazolium bromide ( MTT ) assay. Embryotoxicity was classified according to the prediction model of EST . Results At concentrations >800 μ g/mL MET had a greater cytotoxic effect on D 3 cells than 3 T 3 fibroblasts. At the highest concentration of MET (5 mg/mL), the cell viability of D 3 cells and 3 T 3 fibroblasts was <10% and >30%, respectively. The size of the embryonic body ( EB ) differentiation area was almost the same over the concentration range 50–200 μ g/mL MET , and there was no significant difference in EB differentiation area until a concentration of 400 μ g/mL MET . At a concentration of 800 μ g/mL MET , the size of EB outgrowth was significantly reduced. The same assays revealed GLIM , RSG , and NIM to be weakly embryotoxic substances. Conclusions Based on the EST , MET can be classified as a weakly embryotoxic substance, which suggests that it should be prescribed with caution to pregnant women with gestational diabetes.