Induction of ROS, p38 MAP Kinase and Apoptosis via Pulmonary Toxic Drugs

Abstract

Some drugs may be limited in their clinical application due to their propensity towards their adverse effects. Among these drugs, some clinical chemotherapeutic agents with pulmonary toxic effects were subjected in this study. Moreover, a new paradigm in toxicity screening, toxicogenomic technology represents a useful approach for evaluating the toxic properties of new drug candidates early in the drug discovery process. In this respect, we identified functional mechanisms through analysis of biological process for gene alteration in BEAS-2B cells, human bronchial epithelial cell line, exposed to four drugs-methotrexate (MTX), nitrofurantoin (NF), amiodarone (AM), and carbamazepine (CBZ)-induced pulmonary toxicity, by using human oligonucleotide chip. In this study, we confirmed that pulmonary toxicity-related common mechanisms were apoptosis, cell cycle process, cell development and cell differentiation. Out of common functions, we showed that the treatment with MTX, NF, AM and CBZ resulted in the induction of apoptosis, the increase of ROS generation and the activation of p38 MAPK. Thus, we provide a clue for pulmonary toxic mechanism of these chemotherapeutic agents.