Acetaminophen has gastroprotective effects against lesions induced by nonsteroidal anti-inflammatory drugs in rats. To investigate the mechanisms involved, transcriptome analyses of the ibuprofen-damaged gastric mucosa were performed in the presence and absence of acetaminophen. Ingenuity pathway analysis (IPA) revealed that acetaminophen suppressed the pathways related to cellular assembly and inflammation, whereas they were activated by ibuprofen. On the basis of gene classifications from the IPA Knowledge Base, we identified five genes that were related to gastric damage and showed significant changes in gene expression. The expression of matrix metalloproteinase-13 (MMP-13) was the most reactive, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. These results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play a role.
See article at J Pharmacol Exp Ther 2014, 349:165–173.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics