The chronic cholestasis induce to biliary liver fibrosis (cirrhosis) and the increased products of ROS(reactive oxygen species) cause to the liver damage. In this study ; the antioxidant and antifibrotic effect of dried extracts of oriental medicine (DW) was investigated under the liver fibrotic (cirrhotic) condition. The female Sprague-Dawley rats were divided in 5 groups (Normal, Op-2, Op-4, OpDW-2, OpDW-4). Except for normal group, the rats were induced to biliary liver fibrosis (cirrhosis) by the operation of bile duct ligation/scission (BDU/S) and were observed in 2 weeks or 4 weeks. And the prepared DW was treated p.o.2 ml/day/rats in 2 weeks or 4 weeks for OpDW groups. At the time of sacrifice, the liver, kidney, spleen were weighed and the ratio of organ weight/body weight was calculated. The MDA, the hyp and biochemical parameters (GOT GTP, ALP, t-bili) were measured in sera and liver tissue of rats. The biochemical change was observed on liver tissue. In the result, the hepatomegaly and spleenomegaly appeared in all BDL/S operated rats, and significantly lower liver weight was observed in OpDW-4 group compared with in Op-4 group (p<0.05). The level of clinical parameters in sera of all liver fibrosis (cirrhosis) developed rats was higher than in normal group. Especial1y, the value of GOT in OpDW-2 group and ALP in OpDW-4 group showed significantly lower than in Op-2 group and Op-4 group (p<0.01, p<0.005). The content of hyp in all operation groups was significantly higher than in normal group (p<0.05∼<0.005), and showed significantly lower value in the OpDW-4 group than in Op-4 group (p<0.05). The product of lipid peroxidationUDA) increased significantly under the fibrotic(cirrhotic) condition (p<0.05∼ <0.005), and the MDA value in OpDW-4 group decreased significantly in Op-4 group (p<0.005). The histological change (bile duct proliferation, fibrosis, collagen bundle) was similarly observed in Op-2 group and in OpDW-2 group, but the weak fibrosis and bile duct proliferation were observed in OpDW-4 group compared with in Op-4 group. In conclusion, lipid peroxidation and severe liver damage were activated by bile duct obstruction, and the measurement of MDA and hap can be useful monitor for the screening of antioxidant and antifibrotic effect in experimental liver fibrosis (cirrhosis). The 4 weeks treatment with DW extracts suppressed lipid peroxidation and inhibited fibrotic (cirrhotic) process in BDL/S operated rats.
Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.
The purpose of this study was to investigate the changes in the liver lipid and antioxidant metabolism in obese rats following ingestion of Orostachys japonicus (OJ) hot water extract. The rats were fed a high fat diet for 8 weeks to induce obesity. In the experimental group, 2.5% or 5% OJ hot water extract was added to the diets for 6 weeks. To determine the changes in the liver lipid and antioxidant metabolism in obese rats, the livers were collected and weighed, lipid content was measured, and antioxidant enzyme activity was determined. A significant decrease in liver weight was observed in the group fed with OJ hot water extracts and decreased lipid accumulation was observed in the morphological observation of liver tissue. Total cholesterol and triglyceride contents were also decreased. Both OJ extracts significantly decreased 2,2-diphenyl-1-picrylhydrazyl radical and intracellular reactive oxygen species levels. Further, the levels of the antioxidant enzymes superoxide dismutase and catalase were significantly increased in rats treated with OJ extracts. These results suggest that the intake of OJ hot water extracts may improve liver lipid metabolism by activating antioxidant enzymes.
This study was performed to investigate the effect of Puerariae radix-ethanol extracts rich in isoflavone on the antio-xidative system of rats. For this purpose, first, Puerariae radix was extracted with ethanol, and its total isoflavone and puerarin contents were analysed. Second, female Sprague Dawley rats were fed for 6 weeks with four diets which were based on AIN96G diet and supplemented with Puerariae radix-ethanol extracts to contain isoflavone. The isoflavone contents of four experimental diets were 0 mg, 500 mg, 1,000 mg, 2,000 mg per kg diet, respectively (control, P0.05%,P0.1%, P0.2%). Liver and erythrocyte activities of antioxidative enzyme such as superoxide dismutase (SOD), catalase,glutathione peroxidase (GSHpx) were measured. Also, plasma and liver malondialdehyde (MDA) concentrations, liver glutathione (GSH) and oxidized glutathione (GSSG) concentrations were measured. The total isoflavone content of Puerariae radix-ethanol extract was 3067.6 mg per 100 g extract and the content of puerarin was 2557.4 mg per 100 g extract. The erythrocyte activities of GSH-Px and catalase were higher in group P0.1% and P0.2%. But SOD activity of erythocyte did not show any difference by the Puerariae radix-ethanol extract supplementation in diet. The activity of SOD in liver increased significantly by the supplementation of extract, showing highest level in P0.1% group. The liver GSH concentration increased significantly in group of P0.05%, P0.1%, and P0.2% compared with control group (p <0.05). The GSSG concentration in liver showed no difference by the supplementation of Puerariae radix extract from the control group, except P0.2% group. The plasma MDA concentration did not show any significant differences by the extract supplementation. But the liver MDA concentration decreased by the extract supplementation, showing the lowest level in P0.1 % diet group. These results suggest that the supplementation of Puerariae radix-ethanol extract can inhibit lipid peroxidation in liver and enhance the antioxidative defense competence of rats.
We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and $CCl_4$-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of $CCl_4$-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen ${\alpha}1$(III) and $\beta$-actin mRNA was observed by RTPCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the $CCl_4$-thiopental sod. treated group than that of the normal group (p < 0.01). In the $CCl_4$-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p < 0.001) respectively. The activity of SOD in the $CCl_4$-thiopental sod. treated group is decreased significantly by 44.8% (p < 0.001). And collagen ${\alpha}1$(III) mRNA was more expressed in the $CCl_4$-thiopental sod. treated group than that of the normal group. However, the expression of $\beta$-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in $CCl_4$-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that (1) lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of $CCl_4$-thiopental sod. during a short terms. And (2) the intoxication of $CCl_4$-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and deposition) for test of antioxidant and antifibrotic agent.
Journal of the Korean Society of Food Science and Nutrition
/
제32권1호
/
pp.124-130
/
2003
Effect of Korean red ginseng (KRG) on the level of serum and liver lipids and lipid peroxidation was investigated in the rats fed high fat diet. Content of serum total cholesterol was significantly decreased (P<0.05) in KRG I group and KRG II group. Content of HDL-cholesterol was significantly increased by 69.75% and 39.15% in KRG I and KRG II group compared to control group, respectively. Atherogenic index (hi) was also significantly decreased by 74.76% and 37.38% in KRG I and KRG II groups compared to control group, respectively. Serum triglyceride content was significantly decreased (p<0.05) in only KRG II group. Antioxidative activity of KRG on the lipid peroxidation of serum and tissues in rats was also studied in vivo by measuring the formation of thiobarbituric acid reactive substances (TBARS). Contents of TBARS in the serum of both KRG groups were significantly decreased (p<0.05) and that of nonheme iron in serum was significantly increased (p<0.05) in a dose-dependent manner, which suggested that lipid peroxidation contents are inversely correlated with serum nonheme iron content. Content of TBARS in liver was significantly decreased (p<0.05) in KRG I and KRG II groups, without any influence in other tissues. Content of TBIARS in liver microsomal fractions stimulated by Fe$^{2+}$/ascorbate was significantly decreased (p<0.05) in KRG I and KRG II groups, whereas this observation did not occur in liver mitochondrial fractions. When the effect of KRG on TBARS content in the liver fractions of homogenates, microsomes, and mitochodria stimulated by Fe$^{2+}$/ascorbate was tested in vitro experimental model, TBARS of liver three fractions was significantly decreased at 6 mg/mL KRG compared with those of control. These results suggested that KRG powder have hypocholesterolemic effect as well as antioxidative effect in the serum and liver of the rats fed high fat diet.
This study was undertaken to investigate the effect of the levels of dietary Zn and alcohol consumption on lipid metabolism in Sprague-Dawley male rats weighing 80 to 90g for eight weeks. Ninety rats were divided into nine groups according to Zn levels and alcohol consumption such as no alcohol group[low Zn diet group(<1ppm. LZ) control Zn diet group(30ppm. CZ) high Zn diet group(60ppm, HZ)] 10% alcohol consumption group[the same Zn levels as no alcohol group LZLA, CZLA, HZLA] 20% alcohol consumption group[the same Zn levels as no alcohol group, LZHA, CZHA, HZHA] The results obtained were summarized as following : 1) In the serum total cholesterol increased with increasing dietary Zn levels but decreased with alcohol consumption. HDL-cholesterol decreased with alcohol consumption. Triglyce-ride in alcohol group was higher than no alcohol group. In alcohol group triglyceride increased with decreasing dietary Zn levels. 2) In the liver total lipid in alcohol group was higher than no alcohol group HA group showed a significant increase. Triglyceride increased with alcohol consumption. 3) In the serum and liver Zn content increased with increasing dietary Zn levels but decreased with alcohol consumption.
Effects of a change in dietary Ca content and an alteration in dietary lipid type on lipid metabolism have been investigated in male Sprague-Dawley rats. The results obtained were summarized as follows ; 1) There was no comparable changes in food consumption and body weight gain among all 9 groups. 2) Serum total lipids and cholesterol were lowest when high Ca-corn all diet was fed, and highest when low Ca-butter diet was fed. 3) The contents of total lipids and cholesterol per g liver and total liver showed no consistent tendency with the dietary treatment. 4) Addition of Ca to the diet caused the significant increase in the dry fecal matter and fecal Ca. And fecal total lipids and fecal cholesterol were much greater if the high-Ca diet was fed than if control and low-Ca diet were fed. It is concluded that Ca and polyunsaturated acids have tendency of hypocholesterolemic effect.
This study was conducted to compare the effects of n-6 linoleic acid and n-3 linolenic acid on lipid peroxidation and the activities of enzymes defending against oxidation, which are involved in the tumor promotion, and histolOgical changes of hepatocarcinogen treated rat liver. In this study, weanling male Sprague-Dawley rats were fed one of three diets, containing 15% (w/w) of beef fat (BF), com oil (CO) or perilla oil (PO), for 11 weeks. During the 3rd week, experimental groups were injected with 2-AAF (50 mg/kg of BW) intraperitoneally 3 times. Findings show that the com oil diet group has greater liver MDA content than the beef fat and perilla oil diet groups. Also, it is observed that the perilla oil diet group has lower MDA content than beef fat and com oil diet groups, even though perilla oil is more desaturated than beef fat and com oil. In terms of activity, mixed-function oxidase activity is not Significantly affected by the different dietary fats and 2-AAF treatment. GSH-peroxidase, GSH-reductase and GSH-Stransferase activities are significantly higher in the CO+AAF group than those of the other groups. GST and GSH-Px are activated by 2-AAF treatment in the com oil diet group only. The hepatocytes of the BF+AAF group were the most severely degenerated, the second was the CO+AAF group and the least was the PO+AAF group. It was also found that dietary com oil increased lipid peroxidation and activated defense enzymes against oxidation in liver, but dietary perilla oil did not, or supressed defense enzymes. Therefore it is concluded that dietary n-3 linolenic acid in perilla oil inhibits lipid peroxidation and carcinoenesis in rat liver following 2-AAF treatment.
Objectives : This study was purposed to the anti-oxidative effects of Polygonati Multiflori Caulis(henceforth PMC) on oxidized brain and liver cells in rats. Methods : After extraction of PMC with water, the water extract was divided into five fractions : hexane, ethyl ether, ethyl acetate, butanol and an aqueous fraction. The phenol contents of each fraction were measured. The lipid peroxidation inhibition effect were then investigated. Results : After processing PCM water and PCM fractionations on oxidized brain cells in rats, the SOD (super oxide dismutase) activity and glutathione content were increased, and the NO (nitric oxide) content was decreased. It had much higher SOD activity than liver cells in rats excluded in the n-BuOH and aqueous fractions. In case of oxidized liver cells in rats, the SOD activity and glutathione content increased, while both the NO content and the MDA (malondialdehyde) content decreased. It had much higher glutathione content than brain cells in rats in the every fractions. It had much lower MDA content than brain cells in rats in the Aqueous fractions and brain cells in rats had much lower MDA content than liver cells in rats in the total extract, n-hexane, EtOEt, EtOAc and n-BuOH fractions. Conclusions : PMC has anti-oxidative effect on oxidized liver cells and brain cells in rats, through there are differences in fraction. Additionally, Anti-oxidative effect of brain cells can be relaxed the mental nerve and it is related PMC effect.
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