Potential anticancer effect of red spinach (Amaranthus gangeticus) extract

The objective of this study was to determine the anti cancer effects of red spinach (Amaranthus gangeticus Linn) in vitro and in vivo. For in vitro study, microtitration cytotoxic assay was done using 3-(4,5-dimethylthiazol-2-il)-2,5-diphenil tetrazolium bromide (MTT) kit assay. Results showed that aqueous extract of A gangeticus inhibited the proliferation of liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). The IC(50) values were 93.8 mu g/ml and 98.8 mu g/ml for HepG2 and MCF-7, respectively. The inhibitory effect was also observed in colon cancer cell line (Caco-2), but a lower percentage compared to HepG2 and MCF-7. For normal cell line (Chang Liver), there was no inhibitory effect. In the in vivo study, hepatocarcinogenesis was monitored in rats according to Solt and Farber (1976) without partial hepatectomy. Assay of tumour marker enzymes such as glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), uridyl diphosphoglucuronyl transferase (UDPGT) and alkaline phosphatase (ALP) were carried out to determine the severity of hepatocarcinogenesis. The result found that supplementation of 5%, 7.5% and 10% of A. gangeticus aqueous extract to normal rats did not show any significant difference towards normal control (P <0.05). The exposure of the rats to chemical carcinogens diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) showed a significant increase in specific enzyme activity of GGT, GST, UDPGT and ALP compared to normal control (P <0.05). However, it was found that the supplementation of A. gangeticus aqueous extract in 5%, 7.5% and 10% to cancer-induced rats could inhibit the activity of all tumour marker enzymes especially at 10% (P <0.05). Supplementation of anti cancer drug glycyrrhizin at suggested dose (0.005%) did not show any suppressive effect towards cancer control (P <0.05). In conclusion, A. gangeticus showed anticancer potential in in vitro and in vivo studies.     

Chemopreventive effect of indole-3-carbinol on induction of preneoplastic altered hepatic foci

Indole-3-carbinol (I3C) is a cleavage product of glucobrassicanin, a natural compound present in a wide variety of plant food substances including members of the family Cruciferae. I3C is known to possess cancer-chemopreventive potential in various animal models. The present study reveals the protective effect of I3C on the development of diethylnitrosamine (DEN)-initiated and 2-acetylaminofluorene (AAF)-promoted preneoplastic, altered hepatic foci (AHF) in Wistar rats. I3C was given at dose levels of 0.5 and 1 mg/kg body weight for five consecutive days along with DEN and AAF. AHF were scored and analyzed by quantitative stereology using the Image Analysis System from frozen liver sections stained for positive and negative biological markers of AHF, that is, glutathione S-transferase (GST-P), gamma-glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), adenosine triphosphatase (ATPase), and alkaline phosphatase (AlkPase). Results revealed the chemopreventive effect of I3C on the DEN-initiated AHF in Wistar rats. The expression of G6Pase, ATPase, and AlkPase was restored in the I3C-supplemented animal. Similarly the induced expression GST-P and GGT also decreased in the animals with I3C administration. The recovery of altered levels of these biomarkers was of comparatively higher magnitude in the animals given a higher dose of I3C (1 mg/kg body weight) in comparison with the animals given 0.5 mg/kg body weight dose of I3C, although no dose-dependence pattern was recorded in I3C-supplemented groups. These results thus suggest the chemopreventive effect of I3C in rat hepatocarcinogenesis by suppressing DEN- and AAF-induced AHF development.     

Effect of packaging materials and temperatures on vitamin A and C of flavored aloe vera juice

Aloe vera juice was prepared from aloe vera gel. The standardization of aloe vera juice was done using six different treatments with strawberry and vanilla. Sensory overall acceptability of the product blended with sugar in the ratio of 50:50 was most promising. The juice was packed using three different packaging materials (viz., plastic bottle, glass bottle, and tetra pack) and stored at 5 and 10 °C, respectively. For increasing the shelf life of juice by the above treatment, the hurdle technology was employed. In hurdle technology two methods of preservation, chemical and physical methods were used. Physical method included pasteurization while chemical method involved the use of class II preservatives viz., citric acid, sorbic acid, sodium benzoate, and ascorbic acid. Chemical treatment was more efficient for vitamin A and C.     

Efficacy of dietary aloe vera supplementation on hepatic cholesterol and oxidative status in aged rats

In the current study, we show the anti-oxidative and hypocholesterol effects of aloe vera in the liver. Male specific pathogen-free (SPF) Fischer 344 rats were randomly assigned to one of four groups: Group A (control) was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% (per weight basis) freeze-dried aloe filet; Group C was fed a diet containing a 1% (per weight basis) charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed freeze-dried, whole leaf aloe (0.02% per weight basis) in the drinking water. Our results show that a life-long intake of aloe had superior anti-oxidative action against lipid peroxidation in vivo, as indicated by reduced levels of hepatic phosphatidylcholine hydroperoxide. Additional anti-oxidative action was evidenced by enhanced superoxide dismutase (SOD) and catalase activity in groups B and C. Furthermore, our study revealed that hepatic cholesterol significantly increased in the control group during aging in contrast to the aloe-supplemented groups, which showed approximately 30% lower cholesterol levels, thereby an effective hypocholesteremic efficacy. In this report, we suggest that life-long dietary aloe supplementation suppresses free radical-induced oxidative damage and age-related increases in hepatic cholesterol.     

Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P<.05) in the specific activities of ALP, GGT, and GST between the C and N groups. However, GR activity for the C group was not significantly different compared with the N group. In the CE group, the specific activities of ALP, GGT, GST, and GR were significantly lower (P<.05) compared with the C group. The findings showed that CLE could lower the activity of tumor marker enzymes of rats during hepatocarcinogenesis. Based on the results obtained, polyphenol compounds present in the cacao liquor, extracted by using ethanol, have the potential in decreasing the severity of hepatocarcinogenesis.     

藻毒素对实验性大鼠肝癌的促进作用

目的 研究藻毒素在实验性大鼠肝癌诱导过程中的促进作用。方法 以二乙基亚硝胺(DEN)为启动剂，藻毒素为促进剂，构建大鼠肿瘤促进模型(Solt-Farber模型)，观察肝脏病理形态改变，分别运用免疫组化法和RT-PCR、原位杂交法检测肝细胞中GSTPi蛋白和GSTPi mRNA表达情况。结果 实验组动物肝脏产生结节性增生灶，藻毒素单独作用不能诱导GSTPi mRNA及蛋白表达，但能够促进DEN诱导产生的GSTPi mRNA及蛋白表达，使其表达增加，并具有一定的剂量-反应关系。结论 藻毒素对实验性大鼠肝癌的发生具有促进作用，提示具有促癌活性。     

Antioxidant effect of Hemidesmus indicus on ethanol-induced hepatotoxicity in rats

The antioxidant effect of the ethanolic root extract of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant used in soft drinks in India, was studied in rats with ethanol-induced hepatotoxicity. Administering 20% ethanol (5 g/kg of body weight/day) for 60 days to male Wistar rats resulted in significantly decreased body weight and increased liver/body weight ratio. The liver marker enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatae (ALP), gamma-glutamyl transpeptidase (GGT), and lactate dehydrogenase (LDH), were elevated. In addition, the levels of plasma, erythrocyte, and hepatic thiobarbituric acid-reactive substances (TBARS), hydroperoxides (LOOH), and conjugated dienes (CD) were also elevated in ethanol-fed rats as compared to those of the experimental control rats. Decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C, and alpha-tocopherol (vitamin E) were also observed in ethanol-administered as compared to control rats. Ethanolic root extract of H. indicus was administered at a dose of 500 mg/kg of body weight/day for the last 30 days of the experiment to rats with ethanol-induced liver injury, which significantly increased body weight, significantly decreased the liver/body weight ratio, AST, ALT, ALP, GGT, and LDH activities, and also the levels of TBARS, LOOH, and CD, significantly elevated the activities of SOD, CAT, GPx, and GSH in plasma, erythrocytes, and liver, and also increased levels of plasma and liver vitamin C and vitamin E at the end of the experimental period as compared to those of untreated ethanol-administered rats. Thus, our data indicate that treatment with H. indicus extract offers protection against free radical-mediated oxidative stress in plasma, erythrocytes, and liver of animals with ethanol-induced liver injury.     

In Vivo Evaluation of Eclipta alba Extract as Anticancer and Multidrug Resistance Reversal Agent

The present study investigates the anticancer and multidrug resistance (MDR) reversal potential of hydro-alcoholic Eclipta alba extract (EAE) through in vivo experiments. Diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were used for liver cancer induction in animal model, whereas for MDR induction, AAF was used. The level of antioxidant enzymes was studied in serum along with biochemical parameters. Cancer and MDR-induced liver cells have higher levels of reactive oxygen species (ROS) and, in turn, are responsible for the maintenance of the cancer phenotype. Treatment with EAE declines the ROS level and revealed the ROS scavenging properties. Alfa feto protein levels were found to increase significantly in cancer-induced animals confirming induction and progression of liver cancer, EAE treatment was found to bring back the altered levels within normal range indicating the therapeutic effect of plant extract over liver cancer. Zymogram showed the inhibition of MMPs and RT-PCR analysis revealed that the mRNA expression of nuclear factor-kB was markedly decreased upon EAE treatment. Further, our results showed that EAE could significantly inhibit mdr1 gene encode P-glycoprotein expression. Our data suggest that EAE is a novel anticancer and potent MDR reversal agent and may be a potential adjunctive agent for tumor chemotherapy.     

Anticlastogenicity and Anticarcinogenicity of Purple Rice Extract in Rats

Oryza sativa L. var. indica cv. Kum Doi Saket is a pigmented rice variety grown in northern Thailand. Our previous study found that the methanol extract of purple rice seed had the highest level of antimutagenicity in a Salmonella mutation assay. The present study was designed to evaluate its in vivo anticlastogenic and anticarcinogenic potentials. The purple rice extract had no acute toxicity on rats. The oral administration of 1,000 mg/kg body weight (bw) of the extract for 28 days did not increase the number of micronucleated hepatocytes. Interestingly, it significantly reduced the amount of micronucleus formation in the liver of diethylnitrosamine (DEN)-treated rats. The inhibitory mechanism involved the induction of hepatic glutathione S-transferase (GST) activity. In addition, oral administration of 500 mg/kg bw extract for 10 weeks significantly decreased the number of hepatic GST placental form positive foci, but did not modulate the number of colonic aberrant crypt foci in DEN- and dimethylhydrazine-initiated rats. In conclusion, the methanol extract of purple rice seed showed no toxicity, clastogenicity, or carcinogenicity in laboratory rats. It did display chemopreventive activity against the early stages of rat hepatocarcinogenesis.     

DNA stability and lipid peroxidation in vitamin E–deficient rats in vivo and colon cells in vitro

Summary Background Fruit and vegetable consumption protects against cancer. This is attributed in part to antioxidants such as vitamin E combating oxidative DNA damage. Anthocyanins are found in significant concentrations in the human diet. However, it remains to be established whether they are bioactive in vivo. Aim To investigate the consequence both of vitamin E deficiency on oxidative damage to DNA and lipids and the cytoprotective effect of nutritionally relevant levels of cyanidin–3–glycoside both in vivo in rats and in vitro in human colonocytes. Methods Male Rowett Hooded Lister rats were fed a diet containing less than 0.5 mg/kg vitamin E or a vitamin E supplemented control diet containing 100 mg d–tocopherol acetate/kg. Half of the controls and vitamin E–deficient rats received cyanidin–3–glycoside (100 mg/kg). After 12 weeks endogenous DNA stability in rat lymphocytes (strand breaks and oxidised bases) and response to oxidative stress ex vivo (H₂O₂; 200 µM) was measured by single cell gel electrophoresis (SCGE). Tissue levels of 8–oxo–7,8–dihydro–2–deoxyguanosine (8–Oxo–dG) were measured by HPLC with EC detection. D–tocopherol and lipid peroxidation products (thiobarbituric acid reactive substances; TBARS) were measured by HPLC. Rat plasma pyruvate kinase and the production of reactive oxygen by phagocytes were detected spectrophotometrically and by flow cytometry respectively. Immortalised human colon epithelial cells (HCEC) were preincubated in vitro with the anthocyanins cyanidin and cyanidin–3–glycoside and the flavonol quercetin (all 50 µM) before exposure to H₂O₂ (200 µM). DNA damage was measured by SCGE as above. Results Plasma and liver d–tocopherol declined progressively over 12 weeks in rats made vitamin E deficient. Lipid peroxidation was increased significantly in plasma, liver and red cells. Reactive oxygen levels in phagocytes and plasma pyruvate kinase were increased. Vitamin E deficiency did not affect DNA stability in rat lymphocytes, liver or colon. Cyanidin–3–glycoside did not alter lipid peroxidation or DNA damage in rats. However, it was chemoprotective against DNA damage in human colonocytes.DNA strand breakage was decreased 38.8 ± 2.2 % after pretreatment with anthocyanin. Conclusion while it is accepted that vitamin E alters lipid oxidation in vivo, its role in maintaining DNA stability remains unclear. Moreover, whereas cyanidin–3–glycoside protects against oxidative DNA damage in vitro, at nutritionally relevant concentrations it is ineffective against oxidative stress in vivo.     

Conclusions

Diets deficient in lipotropes (methionine, choline, and folate) and high in fat increase hepatocarcinogenesis by many chemicals, including aflatoxin B1 (AFB1) and N‐2‐fluor‐enylacetamide (AAF). The increase can be corrected in most cases by lipotrope supplementation, but the degree of correction appears to be influenced by the type of fat in the diet. A lipotrope‐deficient, high‐fat diet also increases dimethylhydrazine carcinogenesis in the colon, an effect due to the dietary fat content, not to lipotrope deficiency. In contrast, mammary carcinogenesis by dimethylbenzanthrene or AAF is decreased or unchanged in rats fed the deficient diet.

Hepatic microsomal oxidase activity, cytochrome P450 and conversion of AFB 1 to a bacterial mutagen all are decreased in assays in vitro using tissues from lipotrope‐deficient rats. However, urine mutagen content is increased after AFB1 treatment, as is urine content of activated AAF. AFB1 binding to hepatic DNA in vivo is unchanged or is slightly decreased. Therefore, there is evidence that the dietary deficiency influences carcinogen activation, but the expression and direction of the effect varies. The deficiency also increases cell division in the liver and decreases hepatic s‐adenosylmethionine; carcinogenesis may be influenced by either or both of those changes.     

芦荟、西洋参和番泻叶联合作用对小鼠润肠通便的功能研究

目的 探究不同配伍剂量的库拉索芦荟全叶冻干粉、番泻叶提取物与西洋参提取物联合使用对小鼠润肠通便的作用及机制。方法 雄性昆明种小鼠120只,按人体推荐量的10倍/20倍设置剂量组,随机分为空白组、模型组、芦荟10倍（133 mg·kg.bw） + 西洋参10倍（42.67 mg·kg.bw） + 番泻叶10倍组（33.33 mg·kg.bw）、芦荟20倍（267 mg·kg.bw） + 西洋参20倍（85.34mg·kg.bw） + 番泻叶20倍组（66.66 mg·kg.bw）、芦荟10倍（133 mg·kg.bw） + 西洋参20倍（85.34mg·kg.bw） + 番泻叶10倍组（33.33 mg·kg.bw）、芦荟10倍（133 mg·kg.bw） + 西洋参10倍（42.67 mg·kg.bw） + 番泻叶20倍组（66.66 mg·kg.bw）。给药14 d,洛哌丁胺混悬液灌胃建立小鼠便秘模型,观察黑便情况、小肠墨汁推进率、GDNF、iNOS mRNA表达和蛋白表达。结果 与模型组相比,各剂量组墨汁推进率均明显增高（F = 6.628;P＜0.01）,各剂量组排便实验结果阳性。与模型组相比,芦荟10倍 + 西洋参10倍 + 番泻叶10倍组和芦荟20倍 + 西洋参20倍 + 番泻叶20倍组GDNF mRNA表达增高（F = 28.377,P＜0.05）,iNOS mRNA表达降低（F = 9.153;P＜0.05）。与模型组相比,空白组、芦荟10倍 + 西洋参10倍 + 番泻叶10倍组、芦荟20倍 + 西洋参20倍 + 番泻叶20倍组GDNF蛋白相对含量比升高（F = 4.760;P＜0.05）;芦荟10倍 + 西洋参20倍 + 番泻叶10倍组iNOS蛋白相对含量比下降（F = 9.585;P＜0.05）。 结论 三种药物联合使用通便效果好,提示库拉索芦荟全叶冻干粉联合西洋参提取物和番泻叶提取物可通过增加GDNF表达、抑制NO产生,促进肠道蠕动。     

Dietary butylated hydroxytoluene protects cytochrome P-450 in hepatic nuclear membranes of rats fed 2-acetylaminofluorene

We previously reported that during hepatocarcinogenesis which is induced by feeding 2-acetylaminofluorene (AAF) there is an early loss of cytochrome P-450 in the nuclear envelope (Carubelli et al., Chem. Biol. Interact. 58, 125-136, 1986). Cytochrome P-450 participates in the activation in addition to the detoxification of xenobiotics; therefore, these findings suggested that AAF may cause the loss of an important defense for the protection of the genetic material of the nucleus against carcinogenic metabolites of AAF generated by microsomal P-450 which, in contrast to the nuclear envelope cytochrome P-450, remains essentially undiminished during early stages of AAF feeding. Because dietary butylated hydroxytoluene (BHT) affords good protection against AAF carcinogenicity, we decided to investigate the possibility that the BHT effect could be mediated through the preservation of nuclear envelope cytochrome P-450. AAF (0.05% wt/wt) was administered in a purified diet with a high content of polyunsaturated fat (20% wt/wt corn oil), which is known to enhance AAF carcinogenicity. These studies showed that BHT supplementation (0.3% wt/wt) of control in addition to the AAF-containing diets resulted in higher levels of nuclear envelope cytochrome P-450. After 16 weeks of AAF feeding, nuclear envelope cytochrome P-450 could not be detected in rats fed BHT-free diet, whereas in the rats fed the diet containing AAF and BHT, measurable amounts of nuclear envelope P-450 were observed. These results are compatible with the hypothesis that nuclear envelope cytochrome P-450 is needed for protection against AAF and that BHT protects nuclear envelope cytochrome P-450.     

Hypoglycemic effect of Aloe vera gel on streptozotocin-induced diabetes in experimental rats

In the present study an attempt has been made to evaluate the presence of hypoglycemic activity in the alcoholic extract of Aloe vera gel. Effects of oral administration of A. vera extract at a concentration of 200 and 300 mg/kg of body weight on (a) normal fasted rats, (b) oral glucose-loaded rats, and (c) streptozotocin-induced diabetic rats have been studied. A. vera extract maintain the glucose homeostasis by controlling the carbohydrate metabolizing enzymes.     

A semipurified diet that suppresses phenobarbital promotion of hepatocarcinogenesis in the rat

Six groups of F344/N female rats were fed either a modified AIN‐76 diet (20% casein, 5 % corn oil, 65% cornstarch, 5% cellulose) (AIN) or a diet formulated by Dr. M. Pariza (PD) (30% casein, 10% partially hydrogenated corn oil, 40% sucrose, 15% cornstarch) beginning four days before 70% partial hepatectomy. One day after the surgery, one group fed each diet was intubated with 10 mg/kg diethylnitrosamine (DEN). One week later, these groups plus one control group fed each diet were given 0.05% phenobarbital in the diet for 6 or 14 months. After the rats were killed, blocks of liver tissue were frozen on dry ice and stored at — 70°C. Three frozen serial sections were stained for γ‐glutamyltransferase, ATPase, and glucose‐6‐phosphatase.

Numbers and volume of altered hepatic foci (AHF) were analyzed by stereological techniques. After 14 months of feeding these regimens, rats initiated with DEN and fed the AIN + PB had significantly greater numbers and a higher percent volume of the liver of most phenotypes of AHF than all other groups, including those fed PD + PB following initiation with DEN. The numbers of AHF exhibiting more complex phenotypes (i.e., scored by more than one marker) remained unaltered between 6 and 14 months. These findings indicate that the effectiveness of PB as a promoting agent in multistage hepatocarcinogenesis is significantly altered when fed with two different diets of known composition. Therefore, dietary composition can be a significant factor in studies of the stage of promotion in hepatocarcinogenesis.     

The Effect of Omega-3 Fatty Acid Supplementation on Serum Adipocytokines,Lipid Profile and Biochemical Markers of Inflammation in Recreational Runners

Background: The study aimed to evaluate the effects of a 3-week ω-3 PUFA supplementation on serum adipocytokines (i.e., adiponectin, leptin), neuregulin-4 (NRG4) and erythrocyte omega-3 (ω-3) fatty acid content, as well as the blood antioxidant defense capacity in non-elite endurance runners. Methods: Twenty-four runners were randomized into two groups: the supplemented group, who received omega free fatty acids extract containing 142 mg of EPA, 267 mg of DHA, 12 mg of vitamin E and 5 µg of vitamin D, each administrated at a dose of six capsules twice a day for three weeks, or the placebo group. Venous blood samples were withdrawn at the start and at the end of the study protocols to estimate serum biochemical variables. Results: A significantly higher ω-3 index and lower AA/EPA ratio was observed after ω-3 PUFA compared to pre-supplementation levels (p < 0.001 and p < 0.001, respectively). An increase in baseline adiponectin and NRG4 levels, as well as a decrease of leptin concentration and lipid profile improvement, were observed in subjects after a ω-3 PUFA diet. The increased ω-3 index had a significant effect on TNFα levels and a serum marker of antioxidant defense. Conclusions: The ω-3 PUFA extract with added vitamin E and D supplementation may have a positive effect on the function of the adipocyte tissue, as well as the ability to prevent cardiovascular complications in athletes.     

芦荟对大鼠肝微粒体脂质过氧化损伤体外模型的影响

目的: 探讨芦荟的抗氧化作用及其剂量效应关系。方法: 通过大鼠微粒体的提取,制备了VC/Fe2+和过氧基异丙苯(CHP)脂质过氧化损伤模型,检测不同剂量芦荟轧汁干预对丙二醛(MDA)含量变化的影响,观察芦荟清除活性氧的抗氧化作用。结果: 在CHP微粒体脂质过氧化激发模型中,各芦荟干预组的MDA含量均较对照组显著降低(P﹤0.01),在VC/Fe2+模型中,低剂量芦荟轧汁干预组与高剂量干预组MDA含量较阳性对照组显著下降(P﹤0.05),并且高剂量组降低更加明显(P﹤0.01)。但中剂量芦荟轧汁组MDA含量反而较阳性对照组有一定的升高。结论: 芦荟轧汁在抗氧化方面存在着双向效应,在一定剂量范围内有着较好的抗氧化作用,可能是芦荟的医疗保健功效的机制之一;但特定的剂量又可激发活性氧的生成。     

Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine.

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.     

Effect of vitamin E on lipid parameters in ovariectomized rats

The risk of cardiovascular disease drastically increases at the onset of menopause, in part, because of rise in blood cholesterol and unfavorable changes in lipid profile. This study was designed to investigate the dose-dependent effects of vitamin E supplementation on lipid parameters in ovariectomized (ovx) rats. Sixty 12-month-old female Sprague-Dawley rats were either sham-operated (sham; one group) or ovx (four groups). All rats were maintained on a semipurified caseinbased diet (AIN-93M; 75 IU vitamin E/kg of diet) for a period of 120 days. Thereafter, ovx rats were placed on one of four doses of vitamin E treatment (75, 300, 525, or 750 IU vitamin E/kg of diet), while the sham group was continued on 75 IU vitamin E/kg of diet for 100 days. Ovariectomy tended to increase (by 24%, P = 0.1) serum non?high-density lipoprotein (HDL) cholesterol and decrease (by 14%, P = 0.1) HDL cholesterol. Vitamin E did not have any significant effects on serum lipid parameters. Liver total lipids were notably increased (P < .001) in ovx animals, and supplementation with vitamin E at 525 IU/kg of diet was able to significantly reduce liver total lipids by 13%. Additionally, ovariectomy caused an increase in serum glucose and liver C18:1 fatty acid concentrations along with decreases in C18:0, C20:4, and C22:6 fatty acid concentrations. These alterations on liver fatty acid profiles were unaffected by vitamin E. The findings of this study suggest that vitamin E supplementation moderately improves lipid parameters in ovarian hormone-deficient rats.     

扶正化瘀方对大鼠肝癌前病变细胞周期调控的影响

目的探讨扶正化瘀方对大鼠肝癌前病变细胞周期调控因子CyclinD1、CDK4蛋白表达的影响,揭示扶正化瘀方治疗肝癌前病变的机制及其效果。方法将80只清洁级SD雄性大鼠随机分为空白组、单纯致癌组、扶正化瘀方组、苦参素组,每组20只。除空白组外,其他组以二乙基亚硝胺（DEN）诱导大鼠肝癌前病变模型,应用扶正化瘀方、苦参素对其诱癌过程实施全程干预,共17周。各组大鼠在饲养l8周后取材,利用免疫组化对CyclinD1、CDK4蛋白表达及肝组织病理形态学进行观察。结果扶正化瘀方组、苦参素组大鼠肝脏病变均明显轻于单纯致癌组,与空白组相比,单纯致癌组大鼠肝组织CyclinD1、CDK4蛋白表达明显增高（P〈0.05）。扶正化瘀方组、苦参素组CyclinD1、CDK4蛋白表达较单纯致癌组均明显减少（P〈0.05）;扶正化瘀方组与苦参素组比较有显著差异（P〈0.05）。结论扶正化瘀方可有效阻断大鼠肝癌前病变,其作用机制可能与下调细胞周期调控因子CyclinD1、CDK4蛋白表达有关。