Curcumin, a major polyphenolic compound of turmeric, is well known to prevent non-alcoholic steatohepatitis (NASH) related to obesity. The aim of the study was to investigate the effect of curcumin on hepatic fibrosis induced by carbon tetrachloride ($CCl_4$) in obese mice. $CCl_4$ was administrated in mice fed a normal diet (ND) or a high fat diet (HFD) for 7 weeks together with or without curcumin. It was conducted to examine for metabolic profiles, adipocyte size, and liver fibrosis by serum biochemistry, histology and immunohistochemistry. Also, Apoptosis of hepatic cells was determined by the TUNEL method. Treatment with curcumin significantly lowered the body weight, fasting glucose, serum AST and ALT, and decreased the adipocyte size, the number of macrophage and mast cells in adipose tissue, and collagen deposition in liver tissue in the HFD+$CCl_4$ group compared with the findings of the HFD+$CCl_4$ group. In contrast, treatment with curcumin on the ND+$CCl_4$ group did not show a significant difference except the body weight and mast cell number when compared with the ND+$CCl_4$ group. Furthermore, curcumin significantly reduced the number of parenchymal apoptotic cells, whereas it increased the number of non-parenchymal apoptotic cells, especially resembling an activated hepatic stellate cell in the liver. Taken together, this data suggests that curcumin might be an effective antifibrotic drug for the prevention of liver disease progression in obese mice. Thus, the development of curcumin as a therapy for obesity and liver fibrosis is supported.
This study was carried out to investigate the effect of LAB (Lactic acid bacteria: Lactobacillus acidophilus, Bifidobacterium bifidum and Streptococcus thermophilus) on detoxication of damaged liver in carbon tetrachloride ($CCl_4$) and ethanol (25%)-treated rats. Rats had been daily (twice a day) pre-treated with saline (0.5 ml/kg: untreated group), $CCl_4$ (0.5 ml/kg: other groups) for 6 days. At seventh day, after treating rat with $CCl_4$ and then, mixture of LAB ($10^{11}$/0.5 ml: LAB group), saline (0.5 ml/kg: untreated group, $CCl_4$ group), and biphenyl dimethyl dicarboxylate (DDB) (50 mg/kg: DDB group) were treated orally with $CCl_4$ for 8 days. Ethanol is treated as the same manner instead of $CCl_4$. To investigate the hepatoprotective effect, rats treated with $CCl_4$ and ethanol were analyzed with serum GOT and GPT level. The GOT and GPT levels of LAB group was lower than the level of $CCl_4$ and DDB group. Especially, compared with data of $CCl_4$ group, GPT activity showed statistically significant result in the significance level of p < 0.05. The LAB group treated with ethanol also showed lower level of GOT and GPT than the other control groups treated with ethanol. The triglyceride level of serum decreased more in a group treated special materials (DDB and LAB group) than ethanol group. As well, the effect of LAB on the antifatigue has been investigated. The animals (10/group) were divided into 4 groups (untreated group, Carrier group, Red-ginseng group, LAB group). Each group was given carrier (0.9 mg/0.2 ml), red ginseng extract (200 mg/kg), and mixture of LAB ($10^{11}$/0.2 ml). Special materials were given for three weeks. After finishing treating through oral, horizontal wire test, rotarod test, and forced swimming test were performed. The time of resistance to fatigue of the group, fed with mixture of LAB, was longer than the time when mice treated with red-ginseng that the effect was already revealed. The result of this study revealed that LAB could decrease hepatocelluar injury compared with rats treated orally with $CCl_4$ and ethanol, and could also decrease fatigue.
To evaluate an effect of xanthine oxidase(XO) reaction system on the carbon tetrachloride($CCl_4$) metabolism, $CCl_4$ was given twice at 0.1ml/100g body wt. at intervals of 18 hour to the rats and those pretreated with allopurinol (50mg/kg. body wt.). The influence of XO on the metabolism of $CCl_4$ was focused on the degree of liver damage and the activities of a $CCl_4$ metabolizing marker enzyme, glucose-6-phosphatase. The increasing rate of liver weight per body weight and the levels of serum alanine aminotransferase to the control group were more decreased in allopurinol-pretreated rats than in those treated with $CCl_4$ alone. The liver XO activities were more increased in $CCl_4$-treated rats than the control group and the $CCl_4$-treated rats pretreated with allopurinol showed a decreased activities of XO compared to the $CCl_4$-treated rats. The type conversion (type D --> type O) rate was more decreased tendency in allopurinol pretreated rats than those treated $CCl_4$ alone. In dialyzed liver enzyme preparations, all of the xanthine oxidase activities: $CCl_4$-treated, allopurinol and $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the control group, but similar Km value. Moreover, $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the group treated with $CCl_4$ alone. In conclusion, it can not be negate the possibility of metabolism of $CCl_4$ by the xanthine oxidase enzyme system.
Seo, Ji-Yeon;Lim, Soon-Sung;Park, Ji-A;Lim, Ji-Sun;Kim, Hyo-Jung;Kang, Hui-Jung;YoonPark, Jung-Han;Kim, Jong-Sang
Nutrition Research and Practice
/
v.4
no.2
/
pp.93-98
/
2010
Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.
The sericin fixation of silk fabrics by epoxy resins was studied in the presence of aqueous salt solution in different solvents at the indicated temperature for the desired time. Heavy weight gains were obtained in the reaction with glycerol diglycidyl ether (EX-313) and ethylene glycol diglycidyl ether (EX-810) catalyzed by potassium thiocyanate in such solvents as carbon tetrachloride and p-chloroethylene. The obtained results were summarized as follows; 1) The tested resins were found similar in reaction behavior to silk fabric. The effect of fixation and weight gains was higher in EX-810 than EX-313. 2) The weight gains were increased with reaction time and temperature, and degumming ratio reached a constant value in 90 min at 70$^{\circ}C$. 3) The weight gains and the degumming ratio reached an equilibrium at 3-5% of epoxy concentration. 4) The weight gains were remarkably influenced and increased by the concentration of salt solution. The degumming ratio reached an equilibrium over 0.5N concentration of salt. 5) The weight gains were increased with the dipping time in gently-sloping. The degumming ratio reached an equilibrium over 15 min dipping. 6) The effect of sericin fixation of hydrophobic solvents, such as Carbon Tetrachloride, p-Chloroeth-ylene, Cyclohexane, Xylene and Toluene, was found suitable. 7) The effect of drying temperature was not remarkable on the weight gains and the degumming ratio. 8) There was a slight decrease in the moisture regain of sericin-fixed silk and it may be possible to maintain the moisture regain in the sericin-fixed silk by the epoxy resins. 9) The results on testing physical properties of sericin-fixed silk fabric were as follows; The crease recovery was almost not different from undegummed fabric, but inferior to degummed fabric. The tensile strength was improving in accordance with the effect of sericin fixation, either the elongation did.
Kim, Jung-Hun;Park, Mi-Jung;Kim, Yo-El;Kim, Jin-Yeong;Sin, Jin-Hee;Park, Su-Young;Jekal, Seung-Joo
Korean Journal of Clinical Laboratory Science
/
v.43
no.4
/
pp.194-204
/
2011
This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.
The interactions of aniline, o-toluidine, o-ethylaniline and o-chloroaniline with iodine in carbon tetrachloride solution have been examined through spectrophotometric measurements. The results indicate that both aniline and the o-substituted anilines examined form one-to-one complexes with I2in solution. The formation constants of the complexes measured at room temperature are 12.8, 9.31, 3.15 and 0.576 l $mole^{-1}$, respectively. Comparison of these results with previous experimental results indicates that the relative stabilities of the $I_2$-amine complexes decrease in the following order: $C_6H_5N(C_2H_5)_2 >C_6H_5N(CH_3)_2 >C_6H_5NH_2 >o-CH_3C_6H_4NH_2 >o-C_2H_5C_6H_4NH_2 >o-ClC_6H_4NH_2$. This may support the conclusion that the relative stabilities of these complexes are explained by the inductive effect and steric hindrance of the substituents.
The purpose of this research is to assess the health risk of pollutants in drinking water and recommend the guidelines and management plans for maintaining good quality of drinking water. This study has been funded as a national project for three years from 1992 to 1995. This study(the second year, 1993-1994) was conducted to monitor 32 species of carcinogenic chemicals such as volatile organic compounds(VOCs), polynuclear aromatic hydrocarbons(PAHs), pesticides and heavy metals of drinking water at some area in six cities of Korea, and evaluate health risk due to these chemicals through four main steps of risk assessment in drinking water. In hazard identification, 32 species of carcinogenic chemicals were identified by the US EPA classification system. In the step of exposure assessment, sampling of raw, treated and tap water from the public water supply system had been conducted from 1993 to 1994, and 32 chemicals were analyzed. In dose-response assessment, cancer potencies, unit risk estimates and virtually safe doses of carcinogens were obtained by TOX-RISK (Version 3.1). In risk characterization of detected chemicals, health risk due to carcinogens such as vinyl chloride, carbon tetrachloride, dichloromethane, 1, 2-dichloromethane, chloroform, benzene and arsenic of tap water in several cities exceeded 10$^{-5}$ level. We suggest that non-regulated chemicals which exceed 10$^{-5}$ excess cancer risk level, such as vinyl chloride, carbon tetrachloride and 1, 2-dichloroethane, should be monitored periodically and be regulated by the Drinking Water Management Act, and database for exposure parameter of our own situation should be established.
Jaboyangyeong-hwan (IAE) has been known as a traditional medicine for the treatment of debility, fatigue, and liver diseases. The hepatoprotective effect of the water extract of Jaboyangyeong-hwan was investigated against carbon tetrachloride ($CCl_4$)-induced hepatic damage. A single intraperitoneal injection of $CCl_4$produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase (AST, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with the JAE extract (300, 600, and 1200 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with $CCl_4$-treated control group. Treatment of rats with $CCl_4$led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of the JAE extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from $CCl_4$administration were inhibited by the pretreatment with JAE extract. These results suggest that JAE water extract can be useful as a hepatoprotective agent.
This study investigated the hepatoprotective effects of mesangi (Capsosiphon fulvecens) in carbon tetrachloride $(CCI_4)$-induced liver injury. Thirty healthy male Sprague-Dawley rats were divided into three groups : the normal (Normal), $CCI_4$-treated $(CCI_4)$, and mesangi-treated (Exp-CF) groups. Administration of $CCI_4$ increased the levels of GOT, GPT, and LDH in serum, while the levels were significantly decreased by the addition of mesangi. Higher levels of HDL-cholesterol were found in the Normal and Exp-CF groups, which has lower levels of total and LDL-cholesterol. Administration of $CCI_4$ also increased IGFBP-1 expression in serum, but it was decreased in the Exp-CF group. This suggests that $CCI_4$ is involved in the change in IGFBP-1 expression via its hepatotoxicity. The results indicate that mesangi has a hepatoprotective effect in rats given $CCI_4$.
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