Protective effects of alpha-tocopherol and ischemic preconditioning on hepatic reperfusion injury.
This study evaluated the effect of alpha-tocopherol (alpha-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with alpha-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. alpha-TC and IPC individually attenuated these changes. alpha-TC combined with IPC (alpha-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by alpha-TC, IPC, and alpha-TC+IPC. These results suggest that either alpha-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but alpha-TC combined with IPC offers no significant additional protection.
Lee
Woo-Yong
WY
College of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Lee
Sun-Mee
SM
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D004195:Disease Models, Animal; D018698:Glutamic Acid / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D019194:Ischemic Preconditioning; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000293:injuries; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D018698:Glutamic Acid; D008315:Malondialdehyde; D000410:Alanine Transaminase; D024502:alpha-Tocopherol; D019803:Glutathione Disulfide