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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Razzaghi-Asl, Nima Seydi, Enaytollah Alikhani, Radin Rezvani, Saba Miri, Ramin Salimi, Ahmad |
| Description | Country affiliation: Iran Author Affiliation: Razzaghi-Asl N ( Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.); Seydi E ( Research Center for Health, Safety and Environment (RCHSE), Department of Occupational Health Engineering, Alborz University of Medical Sciences, Karaj, Iran.); Alikhani R ( Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.); Rezvani S ( Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran.); Miri R ( Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Science, Shiraz, Iran.); Salimi A ( Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Science, Ardabil, Iran. Electronic address: salimikd@yahoo.com.) |
| Abstract | To reduce costly late-phase compound scrubbing, there has been an increased focus on assessing compounds within in vitro assays that predict properties of human safety liabilities, before preclinical in vivo studies. The aim of our study was to answer the questions that whether the toxicity risk of a series of 3-oxobutanamide derivatives could be predicted by using of human lymphocytes and their isolated mitochondria. Using biochemical and flow cytometry assessments, we demonstrated that exposure of lymphocytes and isolated mitochondria to five 3-oxobutanamide derivatives (1-5) did not exhibit remarkable toxicity at low concentrations (50-500µM) but toxicity could be observed at high concentrations (1000 and 2000µM), particularly for N-(5-(4-bromophenyl)-3-isoxazolyl)-3-oxobutanamide (4) and N-(2-benzothiazolyl)-3-oxo butanamide (5). Compounds 4, 5 and partly N-(5-methyl-3-isoxazol yl)-3-oxo butanamide (1) also showed a marked cellular and mitochondrial toxicity while compound 5 displayed superior toxicity. Compound 5 induced cytotoxicity on human blood lymphocytes which was associated with the generation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation and depletion of glutathione. Our results suggested that among assessed compounds, increased toxicity of compound 5 compared to other compounds could be likely attributed to the presence of bromine substituent in 5. Finally our findings proposed that using of antioxidants and mitochondrial/lysosomal protective agents could be beneficial in decreasing the toxicity of 5. |
| File Format | HTM / HTML |
| ISSN | 13826689 |
| Journal | Environmental Toxicology and Pharmacology |
| Volume Number | 51 |
| e-ISSN | 18727077 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2017-03-07 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Environmental Health Discipline Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Toxicology Pharmacology |
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