J Korean Surg Soc.  1999 Dec;57(Suppl):935-946.

Effects of Antioxidants and Nitric Oxide Modulating Factors on Hepatic Ischemic-Reperfusion Injury of Rats

• Rhee JE
• Kim SH
• Shin SD
• Pyo CH
• Suh GJ
• Jung SE
• Youn YK
• Oh SK

Abstract

BACKGROUND: Ischemic-reperfusion injury (IRI) is a clinically important mechanism of cellular damage, which is suspected to be caused by the attack of oxygen radicals generated in a reoxygenation phase. Nitric oxide (NO), which is essential to the endothelial function, has been thought to be a key material in IRI. In hepatic transplantation, IRI is inevitable, but the effect of NO on hepatic IRI has not yet been elucidated exactly. This experiment was designed to evaluate the effects of antioxidants and a NO supplement on hepatic IRI.
METHODS
Male Sprague-Dawley rats were divided into five groups: a sham operation group, a group with ischemic-reperfusion (IR), and a group with vitamin C and vitamin E (VC&VE) administered after IR, a group with L-arginine injected after IR, and a group with NG-nitro-L-arginine (NNLA) injected after IR. IRI was induced by clamping the hepatic portal area for 30 minutes, followed by declamping. To prevent blood congestion in the mesenteric vessel, we had performed a porto-systemic shunt operation 4 weeks before the portal clamping. Biochemical assays (tumor necrosis factor-alpha (TNF-alpha) in serum and malondialdehyde (MDA), catalase activity, superoxide dismutase (SOD) activity, and NO synthase (NOS) activity in liver tissue) were performed after sacrificing five rats of each group, respectively, at one and six hours after reperfusion.
RESULTS
IRI increased the MDA level dramatically and exhausted the catalase and the SOD activities remarkably at 1 hour and 6 hours. The group receiving VC&VE had much lower MDA levels and higher catalase and SOD activities than the IR group did. VC&VE had no significant effect on the NOS activities of the liver tissue. L-arginine administration had a definite antioxidant effect, but the effect was muchlower than that of VC&VE. The antioxidant effect of L-arginine seemed related to a reduction in the catalase exhaustion rather than to SOD exhaustion. Strangely, NNLA had a slight antioxidant effect, but had no effect on either the catalase or the SOD activity.
CONCLUSIONS
Antioxidants and a supplement of NO partially prevented IRI of the liver. This effect is thought to be related to suppression of catalase exhaustion. Blocking NO biosynthesis also had a mild antioxidant effect.

Keyword

Ischemic-reperfusion injury; Nitric oxide; Antioxidant; TNF-alpha; Vitamin C

MeSH Terms

Animals
Antioxidants*
Arginine
Ascorbic Acid
Catalase
Constriction
Estrogens, Conjugated (USP)
Humans
Liver
Liver Transplantation
Male
Malondialdehyde
Necrosis
Nitric Oxide Synthase
Nitric Oxide*
Nitroarginine
Rats*
Rats, Sprague-Dawley
Reactive Oxygen Species
Reperfusion
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Vitamin E
Vitamins
Antioxidants
Arginine
Ascorbic Acid
Catalase
Estrogens, Conjugated (USP)
Malondialdehyde
Nitric Oxide
Nitric Oxide Synthase
Nitroarginine
Reactive Oxygen Species
Superoxide Dismutase
Tumor Necrosis Factor-alpha
Vitamin E
Vitamins