• Title/Summary/Keyword: rat hepatotoxicity

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A Study on Accumulation of Cadmium and Induction of Metallothionein in Organs of Rats by Cadmium and Zinc (카드뮴 및 아연투여에 의한 흰쥐의 장기내 Cadmium 축적 및 Metallothionein 생성변화)

  • 이재형;김정현;김남송;김준현;기노석
    • Journal of Environmental Health Sciences
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    • v.20 no.2
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    • pp.64-72
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    • 1994
  • Tolerance to toxic effects of cadmium (Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats (A, B, C), each consisting of 108 rats, were studied and each group was divided into three subgroups (1, 2, 3), 12 rats for each subgroup. Rats were subcutaneously pretreated with saline (A), CdCl$_2$ (0.5 mg/kg, B), and ZnCl$_2$ (13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with CdCIa (3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play and important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggests that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretteatmerit, served to induced the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

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Effects of Cadmium and Zinc Pretreatment on the Acute Cadmium Toxicity and Metallothionein Induction in Rats (카드뮴 및 아연 전처리가 흰쥐의 급성카드뮴 중독 및 Metallothionein생성에 미치는 효과)

  • 이재형;염정호;강현철;김남송;고대하;기노석
    • Journal of Environmental Health Sciences
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    • v.21 no.3
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    • pp.1-15
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    • 1995
  • Tolerance to toxic effects of cadmium(Cd), including lethality has been shown following pretreatment with cadmium and zinc. This study was designed to determine if tolerance also develops to Cd-induced hepatotoxicity and renal toxicity. Three groups of rats(A, B, C), each consisting of 52 rats, were studied and each group was divided into three subgroups(1,2,3), 28 rats for each subgroup. Rats were subcutaneously pretreated with saline(A), $CdCl_2$(0.5 mg/kg, B), and $ZnCl_2$(13.0 mg/kg, C) during time periods of 5 days. At the end of the period, rats were challenged with $CdCl_2$(3.0 and 6.0 mg/kg) by intraperitoneal injection. As for the cadmium levels in rat tissues after 1,3,5,6 days of pretreatments, it was highest in the liver. Then kidney, heart, blood and muscle followed it in that order. After 24, 48 and 96 hours of intraperitoneal injection by challenge doses the concentration of cadmium in liver and kidney increased proportionally to the increase of challenge dosage. However metallothioneins in liver and kidney were increased by the pretreatment of cadmium and zinc. These data indicate the liver is a major target-organ of acute Cd poisoning, and suggest that cadmium induced hepatic injury, via release of Cd-MT, may play an important role in the nephrotoxicity observed in response to short-term exposure to cadmium. This result suggest that increasing cadmium concentrations, gradually accumulating in liver and kidney as the result of the pretreatment, served to induce the synthesis of metallothionein, thus making them resistant to the challenge from cadmium.

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Improvement Effect of Fermented Silkworm (Bombyx mori L.) Powder against Orotic Acid-induced Fatty Liver in Rats (발효누에분말 투여가 orotic acid 유발 흰쥐에 미치는 지방간 개선 효과)

  • Ahn, Hee-Young;Cha, Jae-Young;Park, Kyu-Rim;Kim, Yu-Ra;Cho, Young-Su
    • Journal of Life Science
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    • v.23 no.6
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    • pp.789-795
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    • 2013
  • Current study was to investigate the potential effects of silkworm, Bombyx mori L. fermented with Bacillus subtilis (BFSP) and Aspergillus kawachii (AFSP) at the 5% (w/w) levels in Sprague-Dawley rats, which was intoxicated with 1% (w/w) orotic acid (OA) for 10 days. The rat group administered silkworm powder showed improvements in fatty liver condition. Consumption of fermented silkworm powder reduced triglyceride concentrations in the liver tissues and serum and increased the serum lipid concentrations to normal levels, thereby aiding in improving fatty liver conditions. These effects were more pronounced in the BFSP than that in SP or AFSP in orotic acid-induced hepatotoxicity and oxidative stress. Based on these results, fermented silkworms are considered to be a material with significant potential for development into a functional health food that can improve fatty liver conditions.

Effects of Chitosanoligosaccharide on the Mouse Hepatotoxicity Induced by Cadmium (카드뮴으로 유발된 생쥐 간독성에 대한 키토산올리고당의 효과)

  • Yoon, Jung-Sik;Roh, Young-Bok
    • Applied Microscopy
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    • v.32 no.4
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    • pp.361-376
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    • 2002
  • This research was conducted to determine the effects of chitosanoligosaccharide on liver poisoning induced by cadmium (Cd). Three groups of mice were used in this research. The group was only injected with cadmium (5.0 mg/kg; i.p.) (group Cd) and the other group was injected with cadmium and chitosanoligosaccharide (0.5% solution) at the same time (group Cd+Chi). In order to investigate the inhibitory action of chitosanoligosaccharide on liver damage, cadmium concentration in liver tissues and metallothionein (MT) concentration were relatively measured. In addition, histological observations were made to determine the morphologic injury of liver tissues. Cadmium concentration in liver tissues was drastically lower in groups Cd+Chi than in group Cd. MT concentration in liver tissues was lower in group Cd than in groups Cd+Chi. As the result of electron microscopic observation, mitochondria in group Cd showed a severe swelling phenomenon, RER fragment and ribosome dropout. However, in groups Cd+Chi, mitochondria with high electron density were distributed and RER forming a typical lamellae with ribosome was observed. From these results, cadmium toxicity on rat liver tissues could be lessened by chitosanoligosaccharide.

Protective Effect of Rutin on Carbon Tetrachloride-Induced Acute Hepatotoxicity in Rats (사염화탄소 투여로 인한 랫드의 급성 간 손상에 대한 루틴의 예방 효과)

  • Hwang, Eui-Kyung
    • Journal of Veterinary Clinics
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    • v.30 no.1
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    • pp.12-16
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    • 2013
  • This study was performed to investigate hepatoprotective effect of rutin on acute hepatic damage induced by carbon tetrachloride in rats. Twenty-four male Sprague-Dawley rats were randomly divided into four groups; normal control group, $CCl_4$ control group, two rutin treatment groups (rutin 200+$CCl_4$ and rutin 400+$CCl_4$). Dissolving vehicles were applied to the rats in the normal control group. The rutin was administrated to the rats in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups at the levels of 200 mg/kg and 400 mg/kg, 3 consecutive days orally, with 24 hours interval before inoculating $CCl_4$. $CCl_4$ was intraperitoneally administered an hour after the last treatment of rutin to the rats in every group except the normal control group. The body weight of rats in $CCl_4$ control group were significantly lower than other groups (p < 0.05), but the liver weight and relative liver weight were higher than normal control group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in sera of rats in $CCl_4$ control group were higher and the levels of total protein, albumin and globulin were lower than the normal group (p < 0.05). The activities of ALT, AST, ALP, GTP, LDH and the level of total bilirubin in rutin 200+$CCl_4$ and rutin 400+$CCl_4$ groups were lower than $CCl_4$ control group (p < 0.05). Therefore the pre-treatment of rutin before $CCl_4$ inoculation in rats effectively inhibited the elevation of serum ALT, AST and total bilirubin which are the parameters of hepatic damage.

Effects of Hydroxybrazilin on Glutathione Depletion Induced by $\textrm{BrCCl}_3$ and Menadione in Cultured Rat Hepatocytes

  • Chang, Eun-Sook;Kim, Seong-Gon;Khil, Lee-Yong;So, Dhong-Su;Chang, Tong-Shin;Kim, Jin-Hyoung;Jeon, Sun-Duck;Moon, Chang-Kiu;Park, Kwang-Sik
    • Environmental Analysis Health and Toxicology
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    • v.11 no.3_4
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    • pp.53-57
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    • 1996
  • In this study we investigated the effect of hydroxybrazilin on glutathione depletion induced by BrCCl$_3$ and menadione in cultured hepatocytes to understand the cellular mechanisms of hepatoprotective effect of hydroxybrazilin. Hydroxybrazilin alone had no effect on total glutathione level and the ratio of reduced glutathione/total glutathione (GSH/(GSSG+GSH)). BrCCl$_3$ dramatically decreased total glutathione level and hydroxybrazilin significantly prevented glutathion depletion by BrCCl$_3$. The ratio of GSH/(GSSG+ GSH) was also decreased by BrCCl$_3$ and recovered by hydroxybrazilin treatment. Menadione decreased total glutathione level and the ratio of GSH/(GSSG+GSH) but hydroxybrazilin showed no significant effects on menadione-induced glutathione depletion. These data suggest that hydroxybrazilin might prevent the hepatotoxicity induced by chemicalderived radicals but not the toxicity linked with oxidative stress.

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Soybean isoflavone extract improves glucose tolerance and raises the survival rate in streptozotocin-induced diabetic rats

  • Shim, Jee-Youn;Kim, Kwang-Ok;Seo, Bo-Hyun;Lee, Hye-Sung
    • Nutrition Research and Practice
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    • v.1 no.4
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    • pp.266-272
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    • 2007
  • The present study evaluated the effect of various dosages of soybean isoflavone extract on body weight changes, glucose tolerance and liver function in streptozotocin-induced diabetic rats. One group of normal rats (normal control) was fed an AIN-76-based experimental diet and four groups of diabetic rats were fed the same diet supplemented with four different levels of soybean isoflavone extract for seven weeks. The daily dosages of pure isoflavone for four diabetic groups were set to be 0 mg (diabetic control), 0.5 mg (ISO-I), 3.0 mg (ISO-II) and 30.0 mg (ISO-III) per kilogram of body weight, respectively. The daily consumption of isoflavone at the level of 3.0mg per kilogram of body weight resulted in the suppression of body weight loss and increased the survival rate of diabetic animals one and half times compared to that of the diabetic control group. Blood glucose levels in a fasting state and after the oral administration of glucose were significantly lower in the ISO-II group during the oral glucose tolerance test. The ISO-II group showed a tendency to elongate the gastrointestinal transit time. The activity of serum aminotransferases, indicator of liver function, was not negatively affected by any intake level of isoflavone. The present study demonstrated that the soybean isoflavone extract may be beneficial to diabetic animals by improving their glucose tolerance and suppressing weight loss without incurring hepatotoxicity at the daily dosage of 3.0 mg per kg of body weight.

Hepatoprotecive Effects of Alnus japonica Extract on Experimental Liver Injury Models (오리나무 추출물(AI-1367)의 간질환 동물모델에서의 간 보호효과)

  • Zhao, Yu-Zhe;Lee, Sung-Hee;Huh, Jae-Wook;Ra, Jeong-Chan;Sohn, Dong-Hwan
    • YAKHAK HOEJI
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    • v.56 no.2
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    • pp.99-107
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    • 2012
  • The protective effect of AI-1367 (Alnus japonica extract) on liver injury was investigated. Primary rat hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon tetrachloride ($CCl_4$), or D-glactosamine (D-GalN). Liver injury was induced by $CCl_4$, D-GalN or MCD (methionine choline deficient)-diet in mouse. The cellular leakage of lactate dehyrogenase and cell viability followed by the treatment of hepatotoxicants were significantly improved by AI-1367 treatment at a concentration range of 5~50 ${\mu}g/ml$ for tBH, 5~50 ${\mu}g/ml$ for D-GalN, and 5~100 ${\mu}g/ml$ for $CCl_4$, respectively. Treatment with AI-1367 (20, 10, 5 mg/kg, p.o.) on liver injury induced by subcutaneous injection of $CCl_4$ or D-GalN reduced significantly the levels of aspartate transaminase and alanine transaminase in serum. Histological observations revealed that fatty acid changes, hepatocyte necrosis and inflammatory cell infiltration in $CCl_4$ (D-GalN)-induced liver injury was improved by administration of AI-1367. AI-1367 treatment (10, 5, 2.5 mg/kg, p.o.) also significantly recovered the body weight change and serum levels of aspartate transaminase, alanine transaminase and triglyceride in liver injury induced by MCD diet. From these results, AI-1367 shows protective effects against tBH, $CCl_4$, D-GalN, or MCD diet-induced hepatotoxicity in vitro or in vivo.

Hepatoprotective activity of terpenoids and terpenoid fractions of Scoparia dulcis L

  • Krishnamurthy, Praveen Thaggikuppe;Bajaj, Jitendra;Sharma, Abhishek;Manimaran, Sellappan;Ravanappa, Prashantha Kumar Bommenahalli;Pottekad, Vijayan
    • Advances in Traditional Medicine
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    • v.10 no.4
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    • pp.263-270
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    • 2010
  • Scoparia dulcis L. is widely used in the traditional system of medicine for treating liver ailments. In the present study the terpenoids and terpenoid fractions isolated from 1:1:1 petroleum ether, diethyl ether and methanol (PDM) extract of Scoparia dulcis L. were tested for their in vitro 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Selected samples from the assay were further tested for their in vitro hepatoprotective activity against $CCl_4$ induced hepatotoxicity in freshly isolated rat hepatocytes. In the in vitro antioxidant study, fractions 7, 11, 13, 14, and 15 and PDM extract show the DPPH radical scavenging activity. The phytochemical screening of all these fractions show the presence of terpenoids. In the in vitro hepatoprotective study all these fractions and the PDM extract significantly prevent the $CCl_4$ induced changes in the aspartate aspartate amino transferase, alanine amino transferase and alkaline phosphatase levels (p < 0.05). The above results are comparable with the standard, silymarin. The results of the study indicate that, the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity and this may be attributed to its free radical scavenging potential, which in turn may be attributed to the presence of terpenoids.

The Effects of Houttuynia cordata on the Hepatic Bromobenzene Metabolizing Enzyme System in Rats and Isolation of Phenolic Compounds (흰쥐의 브로모벤젠대사계에 미치는 어성초의 영향과 페놀성 화합물의 분리)

  • Hur, Jong-Moon;Park, Ju-Gwon;Park, Sung-Jong;Lee, Jong-Ho;Sung, Nak-Ju;Choi, Myeong-Rak;Song, Sang-Ho;Kim, Moon-Sung;Choi, Jong-Won;Park, Jong-Cheol
    • Korean Journal of Pharmacognosy
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    • v.31 no.2
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    • pp.228-234
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    • 2000
  • Effects of Houttuynia cordata on the level of lipid peroxide and the enzyme activities of the liver were investigated in bromobenzene-induced rats. Lipid peroxide content in liver was increased by bromobenzene. It was decreased when the methanol extract from the aerial parts of H. cordata was treated to the rat. The methanol extract reduced the activities of aminopyrine N-demethylase and aniline hydroxylase that increased by bromobenzene, however did not affect glutathione S-transferase activity. The methanol extract recovered the activity of epoxide hydrolase activity that decreased significantly by bromobenzene. We suggest that under our experimental conditions the extract might play an important play in the prevention of hepatotoxicity by reduction of aminopyrine N-demethylase and aniline hydroxylase activities as well as enhancement of epoxide hydrolase activity. Six phenolic compounds have been isolated from H. cordata and identified by means of spectral analysis as protocatechuic acid, quercetin, apigenin, afzelin, hyperoside and quercitrin.

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