| 抄録 |
Nonsteroidal anti-inflammatory drugs（NSAIDs）represent a critically important class of medications useful in clinic. The focus of NSAID use has recently centered on gastrointestinal（GI）side effects as well as cardiovascular toxicity, for which innovative new formula of NSAIDs or combination forms are examined. In our lab, we have recent advances in discovery of potential drugs to rescue from NSAID-induced GI injury；omega-3 polyunsaturated fatty acid（n-3 PUFA）, S-allyl cysteine（SAC）from garlic, autophagy inhibitor including chloroquine, and mesenchymal stem cells（MSCs）. ω3-PUFAs based on their anti-inflammatory and anti-oxidative actions had been prescribed in diverse clinical conditions including inflammatory bowel disease, atherosclerosis, and health promoting purpose as well as cancer prevention purpose. There is no clear result whether the ω3-PUFAs rich in fish oils including docosahexanoic acid（DHA）and eicosapentanoic acid（EPA）can be solving strategy. Using fat-1 transgenic mice generating ω3-PUFA due to genetic overexpression of 6-desaturase, we investigated whether ω3-PUFA can prevent NSAID-induced GI injury and found pronouncing protective outcomes of ω3-PUFA against NSAIDs-induced GI injury. SAC, strong antioxidative substances from garlic extracts, also exerted significant protection from NSAID-induced damages, in which global orchestration of HDAC inhibition was primarily operated. Recently, autophagy and subsequent cell death was reported to be responsible for NSAID injury, by which cholorquine based on autophagic inhibition and smad7 activation significantly rescued from indomethacin-induced gastric injury. In conclusion, combination drug or new formula of NSAIDs will be available in clinic to rescue from NSAIDs-induced GI injury. |
