Yasumasa Furukawa

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.

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.

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.

Effect of dipyridamole on experimental disseminated intravascular coagulation in rats.

Experimental disseminated intravascular coagulation (DIC) can be induced by 4-h sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of dipyridamole against DIC. Before the infusion of endotoxin, 0.5, 5.0 or 50.0 mg/kg of dipyridamole was injected intraperitoneally. The preventive effect against DIC was 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 5.0 or 50.0 mg/kg of dipyridamole. From these results, it was shown that dipyridamole inhibited the aggravation of endotoxin-induced experimental DIC in rats.

Prevention by Methylprednisolone of Disseminated Intravascular Coagulation Induced by Sustained Infusion of Endotoxin in Rats

An experimental model of disseminated intravascular coagulation (DIC) could be induced by a sustained infusion of 100 mg/kg of endotoxin for 4 h. Using this experimental model of DIC, the preventive effect of methylprednisolone against DIC was examined. Rats were injected with methylprednisolone at 0.1, 1.0, 10.0 or 30.0 mg/kg i.p., and thereafter infused continuously with 100 mg/kg/4 h of endotoxin. When compared with rats given no methylprednisolone, the significant prevention was noted in parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the formation of fibrin thrombi in the glomeruli, in rats pretreated with 1.0, 10.0 or 30.0 mg/kg of methylprednisolone.

Immunopetentiators and the protection they give against carbon tetrachloride hepatotoxicity

Immunopotentiators such as BCG, levamisole, PS-K and OK-432 prevent carbon tetrachloride (CCl4) hepatotoxicity, and in spite of exposure to CCl4 the liver tissue levels of thiobarbituric acid (TBA) reactive substances were not increased in rats pretreated with such immunopotentiators.