Ferulic acid attenuates ischemia/reperfusion-induced hepatocyte apoptosis via inhibition of JNK activation.
Ferulic acid (FA), a phenolic compound found in various medicinal plants, has hepatoprotective effects against oxidative stress and inflammation. Here, we investigated the protective effects and the specific mechanisms of FA against hepatocyte apoptosis caused by ischemia/reperfusion (I/R). Mice were treated intraperitoneally with vehicle or FA 30 min prior to 60 min of ischemia. After 5h of reperfusion, serum aminotransferase activities and hepatic lipid peroxidation were elevated and hepatic glutathione content was depleted. These alterations were attenuated by FA. I/R increased caspase-3 activity and release of cytochrome c, and these were suppressed by FA. FA also attenuated the increases in the serum tumor necrosis factor (TNF)-α levels and TNF receptor type 1-associated DEATH domain protein and TNF receptor-associated factor 2 protein expressions. The cytosolic levels of Bcl-2-associated X protein (Bax), truncated BH3 interacting domain death agonist (tBid), and Bcl-2-like protein 11 were upregulated after reperfusion. The increases in Bax and tBid protein expression were attenuated by FA. Moreover, I/R induced c-Jun N-terminal kinase 1 (JNK1) and JNK2 phosphorylation, and FA attenuated the JNK activation. FA protects against I/R-induced hepatocyte apoptosis by attenuating oxidative stress and JNK activation.
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Hyo-Yeon
HY
Kim
Sun-Mee
SM
Lee
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D003373:Coumaric Acids; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D053199:TNF Receptor-Associated Death Domain Protein; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C004999:ferulic acid; D000637:Transaminases; D048670:MAP Kinase Kinase 4; D053148:Caspase 3; D053181:Caspase 8; D005978:Glutathione