TY - JOUR T1 - Protective Effects of Acetaminophen on Ibuprofen-Induced Gastric Mucosal Damage in Rats with Associated Suppression of Matrix Metalloproteinase JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.113.210021 SP - jpet.113.210021 AU - Eriko Fukushima AU - Noriyuki Monoi AU - Shigeo Mikoshiba AU - Yutaka Hirayama AU - Tetsushi Serizawa AU - Kiyo Adachi AU - Misao Koide AU - Motoyasu Ohdera AU - Michiaki Murakoshi AU - Hisanori Kato Y1 - 2014/01/01 UR - http://jpet.aspetjournals.org/content/early/2014/02/04/jpet.113.210021.abstract N2 - Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause gastric mucosal damage as a side effect. Acetaminophen, widely used as an analgesic and anti-pyretic drug, has gastroprotective effects against gastric lesions induced by absolute ethanol and certain NSAIDs. However, the mechanisms that underlie the gastroprotective effects of acetaminophen have not yet been clarified. In the present study, we examined the role and protective mechanism of acetaminophen on ibuprofen-induced gastric damage in rats. Ibuprofen and acetaminophen were administered orally, and the gastric mucosa was macroscopically examined 4 h later. Acetaminophen decreased ibuprofen-induced gastric damage in a dose-dependent manner. 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 highly activated by ibuprofen. Based on gene classifications from the IPA Knowledge Base, we identified the following 5 genes that were related to gastric damage and showed significant changes in gene expression, i.e., IL-1β, CCL2, MMP-10, MMP-13, and FOS. Expression of these salient genes was confirmed using real-time PCR. The expression of MMP-13 was the most reactive to the treatments, showing strong induction by ibuprofen and suppression by acetaminophen. Moreover, MMP-13 inhibitors decreased ibuprofen-induced gastric damage. In conclusion, these results suggest that acetaminophen decreases ibuprofen-induced gastric mucosal damage and that the suppression of MMP-13 may play an important role in the gastroprotective effects of acetaminophen. ER -