Yoshikuni Kudo

Effects of anti-free radical intervention on phosphatidylcholine hydroperoxide in plasma after ischemia-reperfusion in the liver of rats

The present study set out to investigate whether plasma phosphatidylcholine hydroperoxide (PCOOH) levels could accurately reflect lipid peroxidation linking to liver damage due to ischemia--reperfusion. PCOOH is a primary peroxidative product of phosphatidylcholine (PC), which is the most important functional lipid in the hepatocellular membrane, and may mediate oxidative stress. We quantified PCOOH and PC in the plasma and liver of rats subjected to hepatic ischemia-reperfusion by chemiluminescence detecting HPLC (CL-HPLC) method. Plasma PCOOH levels showed no significant rise in either the ischemia only group or in the sham-operation group, compared to controls (0.7 nmol/mL plasma). At 60 min subsequent to reperfusion, the PCOOH levels in plasma and liver, as well as the levels of several serum markers of liver injury [lactic dehydrogenase (LDH), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] increased in proportion to the duration of ischemia (up to 60 min). During periods of reperfusion following 30 min of ischemia, plasma PCOOH increased biphasically (2 nmol/mL; 12-24 hr duration of reperfusion), and generally ran parallel to that in the liver after more than 60 min of reperfusion. Dose-dependent protective effects against warm ischemia (30 min)-reperfusion (12 hr) injury were clearly demonstrated in the groups treated with allopurinol, diclofenac Na, ascorbic acid (V.C), alpha-tocopherol and coenzyme Q10, but not in those treated with r-h-superoxide dismutase or betamethasone. The rises in plasma PCOOH and serum GOT, GPT and LDH of the ischemia-reperfused rats were ameliorated most in the group pretreated with diclofenac Na, and next most in the group pretreated with V.C. These results indicate that the plasma PCOOH levels are a useful index both for liver cell damage induced by oxygen free radicals generated during ischemia-reperfusion, and to investigate the efficacy of drugs against oxidative stress.

Investigation of the renal injury caused by liver ischemia-reperfusion in rats

To explain the mechanism of renal injury caused by liver ischemia-reperfusion, we investigated biochemical and morphological changes in the liver and kidney in rats. After reperfusion following 60 min of liver ischemia, numerous changes were found. The level of serum transaminases and lipid peroxide formation in the liver tissue increased significantly. Electron microscopic studies revealed that most of the hepatocytes had swollen mitochondria and clumping of the nuclear chromatin. The sinusoidal endothelium was disrupted and the sinusoidal lumen was filled with numerous erythrocytes. Blood endotoxin concentration, plasma lipid peroxide levels, and serum β-glucuronidase activities were significantly higher than in the control group. Biochemical and morphological renal injury was also observed. Tissue lipid peroxide levels increased in both the kidney and the liver. Microscopic examination revealed damage to the renal tubules, including interstitial edema, dilatation of the lumen, and granular casts derived from necrotic cells in the proximal convoluted tubule. The levels of urinary N-acetyl-β-d-glucosaminidase (NAG) in the liver ischemia-reperfusion group were also higher than in the control group. These results suggest that the renal injury was caused by an increase in endotoxin, lipid peroxide, and lysosomal enzymes in the blood following the liver injury induced by the ischemia-reperfusion.

Evaluation of esophageal function in patients with gastroesophageal reflux disease using transnasal endoscopy

Background and Aims:  To investigate the utility of a new method of carrying out esophageal manometry using a narrow gauge manometry catheter via a transnasal endoscope.

Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres, protects injury of the liver caused by warm ischemia reperfusion

Effects of Lipo-PGE1, prostaglandin E1 incorporated in lipid microspheres on liver injury caused by ischemia reperfusion were investigated. Lipo-PGE1 (10 micrograms/kg or 3 micrograms/kg) or vehicle was gradually injected twice via portal vein 5 min prior to induction of ischemia and reperfusion. Rats died within 2 d after liver ischemia of 90 min from the group receiving injection of vehicle alone. Lipo-PGE1 had its most profound effect on the survival of animals subjected to liver ischemia followed by reperfusion when given in two doses, one prior to ischemia, and another prior to reperfusion. Lipo-PGE1 markedly suppressed both the increases in plasma PCOOH (phosphatidyl-choline hydroperoxide) levels and the leakage of GOT, GPT, and LDH from the liver during the ischemia reperfusion. These findings suggest that Lipo-PGE1 may have therapeutic applications in treatment of hepatic injury.

A successful case of interferon therapy for hepatitis C virus-related cirrhosis with marked thrombocytopenia.

症例は58歳, 男性. 食道静脈瘤破裂の既往をもつ血小板4.9×104/mm3のC型肝硬変に対してインターフェロン (IFN) 療法を行い完全著効が得られ, 組織学的にも肝線維化の減少が見られた. またIFN療法後, 長期間にわたり食道静脈瘤の再発を認めなかった. 著明な血小板減少をともなうC型肝硬変といえども, ウイルス学的条件や投与法の工夫次第では本症例のように著効が得られ, 患者のQOLの改善が得られる. さらに発癌予防, 肝不全予防, 門脈圧亢進症の進展予防の可能性もあり, 症例によってはIFN療法を一度は検討する必要があると考えられる.