Protective effects of alpha-tocopherol and ischemic preconditioning on hepatic reperfusion injury.

Abstract

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.

• Authors: Woo-Yong Lee, Sun-Mee Lee
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 28 Issue 12 Pg. 1392-9 (Dec 2005) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 16392674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Glutamic Acid
• Malondialdehyde
• Alanine Transaminase
• alpha-Tocopherol
• Glutathione Disulfide

Topics

• Alanine Transaminase (blood)
• Animals
• Antioxidants (pharmacology)
• Disease Models, Animal
• Glutamic Acid (metabolism)
• Glutathione Disulfide (metabolism)
• Ischemic Preconditioning
• Liver (blood supply, drug effects, injuries)
• Liver Diseases (etiology, physiopathology, prevention & control)
• Male
• Malondialdehyde (metabolism)
• Mitochondria, Liver (drug effects, metabolism)
• Mitochondrial Swelling (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (complications)
• alpha-Tocopherol (pharmacology)