Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice.

Green tea contains various antioxidative flavan-3ols (tea catechins), such as (-)-epigallocatechin gallate (EGCg, the major catechin), which exert potent inhibitory effects on LDL oxidation in vitro and ex vivo in humans. In this study, the antiatherogenic effects of tea catechins were examined in atherosclerosis-susceptible C57BL/6J, apoprotein (apo)E-deficient mice. Male apoE-deficient mice (10 wk old) were fed an atherogenic diet for 14 wk; during that time, one group (tea) was supplied drinking water supplemented with green tea extract (0.8 g/L), and another group (control) was offered the vehicle only. The tea extract consisted of the following (g/100 g): EGCg, 58.4; (-)-epigallocatechin (EGC), 11.7; (-)-epicatechin (EC), 6.6; (-)-gallocatechingallate (GCg), 1.6; (-)-epicatechin gallate (ECg), 0.5; and caffeine, 0.4. The estimated actual intake of tea catechin was 1.7 mg/(d. mouse). Tea ingestion did not influence plasma cholesterol or triglyceride concentrations. Plasma lipid peroxides were reduced in the tea group at wk 8, suggesting that the in vivo oxidative state is improved by tea ingestion. Atheromatous areas in the aorta from the arch to the femoral bifurcation and aortic weights were both significantly attenuated by 23% in the tea group compared with the control group. Aortic cholesterol and triglyceride contents were 27 and 50% lower, respectively, in the tea group than in the control group. These results suggest that chronic ingestion of tea extract prevents the development of atherosclerosis without changing the plasma lipid level in apoE-deficient mice, probably through the potent antioxidative activity of the tea.

[Intra-arterial preventive chemotherapy for residual liver after resection of hepatic metastasis from colorectal cancer].

We treated 18 cases with intra-hepatic arterial infusion chemotherapy after resection of hepatic metastasis from colorectal cancer (June 1991-September 1997). Eight cases were H1, 7 were H2, and 3 were H3. Hepatic lobectomy was done in 3 cases, lobectomy + partial resection in 2 cases, and partial resection in 13 cases. All cases received high-dose intermittent 5-FU infusion (WHF = 5-FU 1,000 mg/m2/5 hrs/w) on an outpatient basis. The total frequency of WHF was 4-54 times (average 29), and total 5-FU doses ranged from 6.0 to 81.0 g (average 40 g). The 1- and 5-year cumulative survival rates were 100% and 77.5% in all patients 100% and 87.5% in H1 group and 100% and 64.3% in H2 + H3 group, respectively. There was no significant difference of survival between the H1 and H1 + H3 groups. The 1- and 5-year recurrence rates in residual liver were 5.9% and 14.4%, respectively. One of 2 cases with residual liver recurrence was resected for metastasis again, and the patient is now in a disease-free state. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect for their survival, not only in H1 group but also in H2 + H3 group.

[Complication due to arterial infusion chemotherapy for liver metastasis from colorectal cancer].

OBJECTIVES: Arterial infusion chemotherapy is considered to be an extremely effective treatment for liver metastasis from colorectal cancer in terms of its tumor reduction and preventing recurrence in residual liver after resection. However, there still remain some unclear points as to the influence on hepatic artery and bile duct when this treatment is used over the long term. We report some conclusions obtained by examining cases of hepatic arterial occlusion (stenosis) and biliary complication who received this treatment. MATERIALS AND METHODS: Thirty-six cases who received this treatment over 3 months were the objects of this study, with the aim of direct effect against metastatic focus (21 cases) and prevention of recurrence in residual liver (15 cases). The ages were from 27 to 81; 22 cases were male and 14 were female. Indwelling routes of catheter were gastroduodenal artery (GDA) in 28 cases and femoral artery (FA) in 8 cases. Intermittent high-dose infusion (WHF: 5-FU 1,000 mg/m2/5 hrs qw) was adopted as the method. RESULTS: Hepatic arterial occlusion or stenosis was observed in 12 cases (GDA: 10; FA: 2). There seemed to be no correlation with the total dosage of 5-FU or the number of administrations. Even when hepatic arterial occlusion or stenosis occurred, no change was observed in liver function, and there no death was caused by this. However, CT showed a low-density area followed by atrophy in the right lobe in one case with right hepatic arterial stenosis, despite normal portal blood flow. Of the 6 cases which developed obstructive jaundice, 4 were due to the increase of metastatic focus or lymph nodes, and 1 case without dilatation of bile duct died from suspected sclerosing cholangitis. In this case, ALP had been increasing since 1 month before the onset of jaundice. Another case which developed biloma accompanied by the increase of serum bilirubin improved by discontinuance of chemotherapy. CONCLUSION: Since arterial infusion chemotherapy for liver metastasis from colorectal cancer causes hepatic arterial occlusion (stenosis) at a high rate, early detection of abnormalities by liver function test and imaging diagnosis which leads to early treatment is important.

[Studies on antioxidant effect of Hypsizigus marmoreus. I. Effects of Hypsizigus marmoreus for antioxidant activities of mice plasma].

The antioxidant effects of Hypsizigus marmoreus, one of the most popular Japanese edible mushrooms, were investigated by the use of the augmentation effect of antioxidant activity (AOA) in the mice plasma. An aqueous extract of the mushroom fruit-body was found to have a slight trap activity for peroxyl and alkoxyl radicals. On the other hand, the blood plasma of mice fed with a fodder containing 5-10% of the dried powder of the mushroom extract augmented significantly AOA for alkoxyl radicals. It was suggested from analysis of the plasma by the HPLC post column AOA method that the increase of AOA in the mice plasma was caused by the induction of high molecular weight fractions having AOA produced by feeding Hypsizigus marmoreus. The amount of lipoperoxide in the mice plasma as values of thiobarbituric acid reactive substances showed a tendency to be lowered by intake of Hypsizigus marmoreus. These results suggest that oral administration of the fruit-body of Hypsizigus marmoreus can induce an antioxidant effect in the mice plasma.

Effect of tea (Camellia sinensis L.) on lipid peroxidation in rat liver and kidney: a comparison of green and black tea feeding.

The antioxidant effects in the liver and kidney obtained from rat fed diets containing 3% green or black tea leaf powder, which were prepared from the same lot tea leaves, were studied using the tissue slice-antioxidant evaluation method with two lipid peroxidation inducers. After 50 d on the diets, liver slices prepared from green and black tea-supplemented rats showed significant inhibitory effects against tert-butyl hydroperoxide-induced lipid peroxidation. These effects, however, were not proportional to the amounts of (-)-epicatechins and antioxidant vitamins in the tea leaves. In the kidney, the antioxidant effect was observed only in the green tea-fed group. A similar antioxidant effect on the kidney was observed after oral administration of a major tea polyphenol, (-)-epigallocatechin gallate (50 mg/kg body weight for 7 d). Liver slices from black tea-fed rats also inhibited bromotrichloromethane-induced lipid peroxidation. These results demonstrated that dietary green and black tea had antioxidant effects on tissue lipid peroxidation ex vivo.

The inhibitory effects of tea polyphenols (flavan-3-ol derivatives) on Cu2+ mediated oxidative modification of low density lipoprotein.

Tea polyphenols (flavan-3-ol derivatives) suppressed the oxidative modification of low density lipoprotein (LDL) which is assumed to be an important step in the pathogenesis of atherosclerosis lesions. Inhibitory experiments on the oxidative impairment of porcine serum LDL by flavan-3-ols were carried out by incubating them at 37 degrees C in the presence of 5 microM Cu2+. The oxidation of LDL was monitored either by an absorption increase at 234 nm due to the conjugated diene formation, or the formation of hydroperoxides and thiobarbituric acid reactive substances (TBARS). It was found that the oxidation was strongly inhibited by various flavan-3-ols, and a lag time over 100 min appeared, depending on the types of flavan-3-ols used. The activities based on the prolongation of the lag time were in the order of (-)-epigallocatechin (EGC) < (+)-catechin (C) < (-)-epicatechin (EC) < (-)-epicatechingallate (ECG) < (-)-epigallocatechingallate (EGCG). IC50 of flavan-3-ols on Cu2+ mediated hydroperoxides and TBARS formation of LDL were 0.90, 0.95 microM for ECG and 2.38, 2.74 microM for EGC, respectively. It was found that the Cu2+ mediated cholesterol ester degradation in LDL was almost completely inhibited by 5.0 microM C or EGCG. Cu2+ mediated apolipoprotein B-100 fragmentation was also inhibited (up to 60%) in the presence of C or EGCG.

Antioxidative effects of black tea theaflavins and thearubigin on lipid peroxidation of rat liver homogenates induced by tert-butyl hydroperoxide.

The antioxidative activity of theaflavins (TFs) and thearubigin (TR) purified from the infusion of black tea leaves was examined using the tert-butyl hydroperoxide-induced lipid peroxidation of rat liver homogenates. The concentrations which produced 50% inhibition of lipid peroxidation (IC50) by theaflavin (TF), theaflavin monogallate-A (TFM-A), and TR were 4.88 x 10(-4), 4.09 x 10(-4), and 4.95 x 10(-4%) (w/v), respectively. The anti-oxidative activity of these compounds was higher than that of glutathione, L(+)-ascorbic acid, dl-alpha-tocopherol, butylated hydroxytoluene, butyl hydroxyanisole, etc., but was lower than the activity of (-)-epicatechin gallate, (-)-epigallocatechin, and (-)-epigallocatechin gallate. As to the IC50 in molarity, the antioxidative activity of TFM-A was the second highest among all the samples used in this study. The antioxidative activity of lyophilized tea infusions was compared. The activity of black tea was about as potent as that of green tea. These results suggest that black tea infusion containing TFs and TR could inhibit lipid peroxidation in biological conditions in the same way as green tea infusion containing epicatechins.

Studies on the formation of aliphatic aldehydes in the plasma and liver of vitamin E-deficient rats.

The effects of vitamin E (E) deficiency on the formation of aliphatic aldehydes in rat plasma and liver were studied. Three-week-old Wistar male rats were fed either an E supplemented diet (2-ambo-alpha-tocopheryl acetate 20 mg/kg diet, designated as E supplemented diet group) or an E deficient diet (E deficient diet group). After 8 weeks, n-hexanal and (E)-4-hydroxy-2-nonenal (4-HN) in the plasma of the E deficient diet group were found to be 2.0 and 2.5-fold greater than those of the E supplemented diet group, respectively. The contents of aldehydes such as n-pentanal, n-hexanal, 4-HN in the liver were also significantly higher in the E deficient diet group than in the E supplemented diet group. These results indicate that some aldehydes, arising possibly from lipid peroxides, are produced and detected in the plasma and liver of rats under the condition like E deficiency. In this study we further found that the activity of the liver aldehyde dehydrogenase (ALDH, EC 1.2.1.3) was significantly changed; 5 and 8 weeks after the start it was lower in the E deficient diet group when compared to that in the E supplemented diet group. The decrease of enzyme activity was related to the increase of aldehydes such as n-hexanal in the liver. the aldehyde increase in the plasma of the E deficient diet group was thought to raise the injury of cells, namely, a strong hemolysis on erythrocytes prepared from the blood of rats fed the E deficient diet.

Effect of tea on 12-O tetradecanoyl-phorbol-13 acetate (TPA) induced promotion of transformation in JB6 mouse epidermal cells.

The extract of black and green tea (Camellia sp.) which are widely consumed as commonest beverage, decreased the 12-O-Tetradecanoylphorbol-13 acetate (TPA) induced promotion of transformation in dose dependent manner in JB6 mouse epidermal cell system. The probable mechanisms have been discussed.

Crude tea extracts decrease the mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine in vitro and in intragastric tract of rats.

The effects of tea extracts and their ingredients, catechins and L-ascorbic acid (AsA), on the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were examined in vitro and in the stomachs of rats using E. coli WP2 and S. typhimurium TA100. The extracts of green tea and black tea leaves decreased the mutagenic activity of MNNG to E. coli WP2 in vitro in a desmutagenic manner. Catechins such as (-)-epigallocatechin from green tea leaves and the low-molecular-weight tannin fraction isolated from black tea extract with HP-20 resin also exhibited inhibitory effects against the mutagenic activity of MNNG. A desmutagenic effect of AsA on MNNG-induced mutagenicity was observed depending on the dose, though it was complicated. The effects were also demonstrated in the stomachs of rats by assaying the bacterial mutagenic in vitro; the tea extracts previously given orally to rats reduced the mutagenic activity of MNNG remarkably, though simultaneous administration showed less effect. The effectiveness of tea extracts for the decrease of MNNG-induced mutagenesis in vitro and in vivo suggests that the habitual drinking of tea may reduce the tumor-initiating potency of MNNG-type nitrosoureido compounds if they are formed in the stomach.

Flameless atomic absorption spectrophotometric determination of Vendex, an organic tin miticide, in apples, oranges, and tea leaves.

A method is described for the determination of an organic tin insecticide, Vendex or hexakis(2-methyl-2-phenylpropyl)distannoxane (HMPD). Tin compounds are extracted from the sample homogenate with ethyl ether containing 1% acetic acid. HMPD and its degradation products are separated through a silica gel column, and analyzed by an atomic absorption spectrophotometer coupled with a heated graphite atomizer. By this technique, as little as 5 ng HMPD and its degradation products can be determined with an average recovery of 67-96%.