Shuhei Takemura

Experimental hypoxia and lipid peroxide in rats.

Abstract By feeding under conditions of reduced oxygen supply, the increase in serum, arterial, and brain tissue levels of lipid peroxide in rats was prompted. The arterial-tissue level of lipid peroxide increased with advancing hypoxia, but the brain and serum levels of lipid peroxide were elevated at 2-weeks feeding under conditions of reduced oxygen supply and restored to the values obtained before the onset of the experiment at 4 weeks. In the liver, lipid peroxides due to hypoxia were only slightly increased in liver-tissue level of lipid peroxide. It was indicated by these observations that the possibility exists that hypoxia might be one of the factors predisposing to the accumulation of lipid peroxide, and that peroxidation might occur not only in conditions of excessive supply of oxygen but also in conditions of short supply of oxygen.

Effects of FUT-175, a New Synthetic Protease Inhibitor on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

The effects of FUT-175 (6-amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4-hour sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were infused continuously with FUT-175 at 0.001, 0.01, 0.1, 1.0 or 10.0 mg/kg into a femoral vein for 4 h. Simultaneously with the agent infusion, endotoxin (100 mg/kg/4 h) was administered into the contralateral femoral vein. A protective effect against DIC was noted in the rats treated with 0.01 or 0.1 mg/kg of FUT-175 in the following parameters: fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi. These results demonstrated that FUT-175 reduces the extent of changes of the coagulation parameters caused by DIC.

Experimental Model of Disseminated Intravascular Coagulation Induced by Sustained Infusion of Endotoxin

SummaryExperimental disseminated intravascular coagulation (DIC) was induced by sustained infusion of endotoxin into the femoral vein in rats. The severity of DIC was determined with reference to various parameters, such as fibrinogen and fibrin degradation products (FDP), prothrombin time (PT), partial thromboplastin time (PTT), platelet count, and number of renal glomeruli having fibrin thrombi.Experimental DIC could be induced by a 4-h sustained infusion of endotoxin in a dose of 100 mg/kg. The DIC induced in rats showed a close resemblance to human DIC as judged from such changes as an elevation in FDP, prolongation of PT and PTT, depression in fibrinogen and platelet count, and increase in glomeruli having fibrin thrombi.This experimental model has an advantage in that the severity of DIC can be determined by measuring various parameters. It will be of use in the studies aimed at the establishment of a therapy for DIC as well as in the studies on DIC in rats.

Effects of Vitamin E on D-Galactosamine-Induced or Carbon Tetrachloride-Induced Hepatotoxicity

Experimental liver disorders were induced by the use of carbon tetrachloride or D-galactosamine hydrochloride in rats maintained on a vitamin E deficient diet and in rats fed a diet supplemented with vitamin E, and the protective effect of vitamin E on the liver was determined. After exposure to carbon tetrachloride or D-galactosamine hydrochloride the serum levels of transaminases, lysosomal enzyme beta-glucuronidase, and acid phosphatase were elevated, and thiobarbituric acid reactive substances in serum and liver homogenate were also increased. The changes were conspicuous in the vitamin E deficient rats, but were only slight in rats fed a diet supplemented with vitamin E. The results of this study suggest that vitamin E has a protective effect on liver disorders by inhibiting lysosomal enzyme liberation and lipid peroxidation.

Lipid peroxidation and lysosomal enzymes in D-galactosamine hepatitis and its protection by vitamin E

SummaryRole of Iipid peroxidation on lysosomal instability in liver tissue was investigated in an experimental model of D-galactosamine hepatitis in rats fed on vitamin E (V.E) deficient diet.Administration of D-galactisamine to V.E deficient rats resulted in a sudden increase of serum glutamic oxaloacetic transaminase (sGOT), glutamic pyruvic transaminase (sGPT), lipid peroxide value, as well asβ glucuronidase and acid phosphatase activity examined as markers of lysosomal enzymes, when compared with control rats fed on V.E supplemented diet.Lipid peroxide in the liver tissue also showed significant increase in V.E deficient rats. In contrast, \- glucuronidase and acid phosphatase in the liver tissue were found to decrease in V.E deficient rats by the administration of D-galactosamine, indicating that the enzymes in the lysosome were entirely released outside the liver cells as a result of cell destruction.It is concluded that the increase of lipid peroxide causes the instability of lysosomal membranes and releases various kinds of hydrolytic enzymes to lead further cell damage. V.E might act on inhibiting lipid peroxidation to stabilize lysosomal membranes.

C3b receptor (CR1) on erythrocytes in various diseases

Abstract Complement receptor for C3b (CR1) on erythrocytes was investigated in various diseases by immune adherence hemagglutination (IAHA) using aggregated human IgG. In normal controls, 21 out of 312 (6%) revealed defective CR1 reactivity, and there was no difference in the prevalence of defective CR1 reactivity between female ( 11 157 , 7%) and male ( 10 155 , 6%). Among various diseases examined significantly high prevalence of defective reactivity of CR1 on erythrocytes was seen in systemic lupus erythematosus (SLE) ( 22 30 , 73%) and malignancy of hematopoietic system, especially in acute myelogenous leukemia (AML) ( 6 11 , 55%).

The increase of thiobarbituric acid reacting substances in rats with experimental chronic hypoxia.

Feeding under conditions of reduced oxygen supply prompted an increase in serum, arterial and brain tissue levels of thiobarbituric acid (TBA)-reacting substances. These observations indicated the possibility that hypoxia might be one of the factors predisposing to the accumulation of lipid peroxide.

Protective Effect of Gabexate Mesilate against Experimental Disseminated Intravascular Coagulation in Rats

Experimental disseminated intravascular coagulation (DIC) can be induced by 4 h sustained infusion of endotoxin at a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of gabexate mesilate (GM) against DIC. Before the infusion of endotoxin, 10(-6), 10(-3), 1, 10, 50 or 100 mg/kg of GM was injected intraperitoneally. The preventive effects against DIC were noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1, 10 or 50 mg/kg of GM. From these results it was shown that GM inhibited the aggravation of endotoxin-induced experimental DIC in rats.

Hemorrhagic Necrosis of the Intestinal Mucosa Associated with Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC), experimentally induced by endotoxin, caused severe hemorrhagic necrosis of the intestinal mucosa in dogs. Microscopic observation showed tortuous thrombus formation in the microcirculation of the villi. Ligation of the pancreatic and bile ducts, or administration of heparin protected the mucosa from hemorrhagic necrosis, while systemic administration of tranexamic acid increased the intestinal mucosal lesion. Local pretreatment of the intestinal mucosa by Trasylol or tranexamic acid reduced the degree of hemorrhagic necrosis. It is concluded that intravascular coagulation in the microcirculation of the intestinal mucosa, as well as pancreatic proteases, play a role in the pathogenesis of hemorrhagic necrosis in the intestine associated with DIC.

The protection of coenzyme Q10 against carbon tetrachloride hepatotoxicity.

SummaryIt has been suggested that lipid peroxidation is an important factor in the pathogenesis of carbon tetrachloride (CC4) hepatotoxicity.In the present study, experimental liver injury induced by CC14 could be inhibited by Coenzyme Q10 (CoQ10) and in spite of exposure to CCI4 the liver tissue levels of thiobarbituric acid (TBA) reacting substances were not increased in rats pretreated with CoQ10.In the in vitro experiment as well, the apparent liver tissue levels of TBA were decreased after addition of C0Q10.These facts provided evidences that CoQ10 possessed a direct antioxidative effect and protected against CCI4 hepatotoxicity by this antioxidative effect.