• 제목/요약/키워드: liver toxicology

검색결과 539건 처리시간 0.025초

Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

  • Harada, Takanori;Takeda, Makio;Kojima, Sayuri;Tomiyama, Naruto
    • Toxicological Research
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    • 제32권1호
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    • pp.21-33
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    • 2016
  • Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p'-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT.

Arsenite-induced Hepatotoxicity in Chang Liver and Clone 9 Cells

  • Yum, Young-Na;Ahn, Jin-Hong;Kim, Gi-Dae;Hwang, Myung-Sil;Kim, Sheen-Hee;Lim, Chul-Joo;Yang, Ki-Hwa;Kim, Dae-Kyung;Cho, Dae-Hyun
    • 한국환경성돌연변이발암원학회:학술대회논문집
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    • 한국환경성돌연변이발암원학회 2003년도 춘계학술대회
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    • pp.56-56
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    • 2003
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Synthesis and Antioxidant Properties of Some Novel Benzimidazole Derivatives on Lipid Peroxidation in the Rat Liver

  • Canan Kus;Gulgun, Ayhan-Kilcigil;Eke, Benay-Can;Mumtaz Iscan
    • Archives of Pharmacal Research
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    • 제27권2호
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    • pp.156-163
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    • 2004
  • Some benzimidazole derivatives namely 1-[(substituted thiocarbamoylhydrazine carbonyl) methyl]-2-phenyl-1 H-benzimidazoles (1a-13a), N-[(2-phenylbenzimidazol-1-yl methyl)-[1,3,4]-thiadiazole-2-yl]-substituted phenyl amines (1b-13b) and 5-(2-phenyl benzimidazol-1-yl-methyl)-4-substituted phenyl-4H-1,2,4-triazole-3-thiones (1c-13c) were synthesized, and their in vitro effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined. The most active compound 10a caused an 84% inhibition of LP at $10^{-3}$ M, which is better than that of butylated hydroxytoluene (BHT) (65%).

In Vitro and in Vivo Metabolism of Salsolinol, on Endogenous Isoquinoline Neurotoxin, in Rats

  • Rhee, Hee-Kyung;Kwon, Oh-Seung;Ryu, Jae-Chun
    • 한국환경성돌연변이발암원학회지
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    • 제21권1호
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    • pp.30-33
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    • 2001
  • Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, SAL), a dopaminergic isoquinoline neurotoxin, has been implicated to contribute the etiology of Parkinson's disease and neuropathology of chronic alcoholism. In our previous results, SAL was reported to have the mutagenicity and clastogenicity not in bacteria but in mammalian cells, and its genotoxic potential was known to be potentiated in the presence of rat liver S-9 fraction. This may indicate that some metabolite(s) of SAL was involved in the mutagenic potentials. To investigate the SAL metabolites, the metabolism studies of SAL were conducted in vitro rat liver S-9 fraction and in vivo using rats by high performance liquid chromatography and gas chromatography/mass spectrometry. The methylated metabolite of SAL was found in urine of rats, while the same methylating form of metabolite was not produced from the in vitro metabolism system using rat liver S-9 fraction.

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Promotion of Liver Lesion Development in the Syrian Hamster by Deitary fat Following Multi-Organ Initiation is Inhibited by Dhea-S Administration

  • Park, Cheol-Beom;Kim, Sun-Hee;Shim, Young-Hee;Kim, Dae-Joong;Lee, Jong-Sung;Park, Jong-Il;Kang, Jong-Koo;Moore, Malcome.A.;Iroyuki, Tsuda.H.
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2003년도 추계학술대회
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    • pp.118-118
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    • 2003
  • The influence of dietary supplementation with dehydroepiandrosterone-sulphate (DHEA-S) at 0.6% was investigated in male Syrian golden hamsters initiated by treatments with azoxymethane(AOM), and dihydroxy-di-n-propyl nitrosamine (DHPN), timed after transfer from a choline-deficient to a normal diet.(omitted)

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Morin alleviates fructose-induced metabolic syndrome in rats via ameliorating oxidative stress, inflammatory and fibrotic markers

  • Heeba, Gehan Hussein;Rabie, Esraa Mohamed;Abuzeid, Mekky Mohamed;Bekhit, Amany Abdelrehim;Khalifa, Mohamed Montaser
    • The Korean Journal of Physiology and Pharmacology
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    • 제25권3호
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    • pp.177-187
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    • 2021
  • Metabolic syndrome (MBS) is a widespread disease that has strongly related to unhealthy diet and low physical activity, which initiate more serious conditions such as obesity, cardiovascular diseases and type 2 diabetes mellitus. This study aimed to examine the therapeutic effects of morin, as one of the flavonoids constituents, which widely exists in many herbs and fruits, against some metabolic and hepatic manifestations observed in MBS rats and the feasible related mechanisms. MBS was induced in rats by high fructose diet feeding for 12 weeks. Morin (30 mg/kg) was administered orally to both normal and MBS rats for 4 weeks. Liver tissues were used for determination of liver index, hepatic expression of glucose transporter 2 (GLUT2) as well as both inflammatory and fibrotic markers. The fat/muscle ratio, metabolic parameters, systolic blood pressure, and oxidative stress markers were also determined. Our data confirmed that the administration of morin in fructose diet rats significantly reduced the elevated systolic blood pressure. The altered levels of metabolic parameters such as blood glucose, serum insulin, serum lipid profile, and oxidative stress markers were also reversed approximately to the normal values. In addition, morin treatment decreased liver index, serum liver enzyme activities, and fat/muscle ratio. Furthermore, morin relatively up-regulated GLUT2 expression, however, down-regulated NF-κB, TNF-α, and TGF-β expressions in the hepatic tissues. Here, we revealed that morin has an exquisite effect against metabolic disorders in the experimental model through, at least in part, antioxidant, anti-inflammatory, and anti-fibrotic mechanisms.

Mouse에 있어서 Ethanol의 간독성에 미치는 Capsaicin의 영향 (Effects of Capsaicin on the Liver Toxicity of Ethanol in Mice)

  • 안영근;김정훈;이선원;김성오
    • Environmental Analysis Health and Toxicology
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    • 제3권1_2호
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    • pp.21-31
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    • 1988
  • The effect of capsaicin on the toxicity of ethanol in mice were studied. Capsaicin was administered i.p. every other day for 4 weeks and 5% ethanol was provided ad libitum by tap water for 4 weeks. The administration of capsaicin 3.0 mg/kg showed the increase of body weight gain, ratio of liver wt./body wt., s-GPT. s-triglyceride and s-cholesterol, and showed the decrease of BUN as compared to control group. Capsaicin administered 3.0 mg/kg showed severe moth eaten appearance. eosinophilic necrosis and cholangitis in mouse liver The administration of 5% ethanol showed the decrease of body weight gain, ratios of liver, kidney and spleen wt./body wt., s-tryglyceride and s-cholestrol. Ethanol administered 5% solution showed little fatty change, moth eaten appearance, Kupffer cell proliferation, spotty necrosis and nuclear regeneration. The administration of capsaicin and ethanol together decreased the influence of ethanol on body weight gain, ratios of liver, kidney and spleen wt./body wt., s-triglyceride and s-cholesterol, and showed the less severe moth eaten appearance, eosinophilic necrosis and cholangitis. It might be concluded that the administration of capsaicin and ethanol together decreased the toxicity caused by capsaicin or ethanol respectively.

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Toxicoproteomic Analysis of Differentially Expressed Proteins in Rat Liver by DEHP

  • Son, Bu-Soon;Seong, Ah-Reum;Park, Seul-Ki;Kim, Wan-Jong;Ryu, Jae-Chun;Lee, Mi-Young
    • Molecular & Cellular Toxicology
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    • 제3권4호
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    • pp.299-305
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    • 2007
  • The endocrine disrupting chemical, di (2-ethylhexyl) phthalate (DEHP) is a plasticizer used in polyvinyl chloride products ubiquitous in our daily lives. DEHP has potentially adverse effects on the liver, kidney, lung, heart, reproductive organs and endocrine systems. Many toxicological data on the DEHP toxicity have been stated, but complete protein profiles have not yet been reported. In this study, DEHP-induced oxidative DNA damage in rat lymphocyte was evaluated by Comet assay (single-cell gel electrophoresis) for the first time. Moreover, DEHP-induced protein profile alterations were examined in rat liver by using toxicoproteomic tools. 34 protein spots in the liver were identified to be significantly deregulated by DEHP on the 2-dimensional gel. Among them, 20 spots were up-regulated and 14 spots down-regulated by DEHP.

N-(2-Ethylhexyl)-8, 9, 10-trinorborn-5-ene-2, 3-dicorhoxymide가 Rat의 Cytochrome P-450 및 생화학적 혈액상에 미치는 독성작용 (The Toxicity of N-(2-Ethylhexyl)-8, 9, 10-trinorborn-5-ene-2, 3-dicorhoxymide on Cytochrome P-450 and Biochemical Parameter of Serum in Rats)

  • 홍사욱;장준식
    • Environmental Analysis Health and Toxicology
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    • 제7권1_2호
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    • pp.1-16
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    • 1992
  • Biologically, MGK-264 (N-octyl bicycloheptene dicarboximide) acts as a synergists for insecticides mainly pyrethrins and pyrethroids. It's used extensively in combination with pyrethrin and piperonyl butoxide and also with personal insect repellent and cockroach repellents. But the toxic effect of MGK-264 in mamalians was a relatively little known therefore in this studies it was initiated to examine the toxic effect of MGK -264 in rats. For 5 weeks it administrated daily in each 250 mg and 500 mg of MGK-264 per kg of body weight in rats. 1) The body weight gain and the LYMPH (%) value in blood were observed a slight tendency to reduce in accordance with amount of dose and number treatment time. 2) The content of cytochrome P-450 and activity of NADPH-cytochrome c reductase were decreased in liver and those were observed some tendency in the kidney as liver but not significant. 3) The liver cholinesterase activity in the both 250 mg/kg and 500 mg/kg per kg of body weight with treated groups and the liver aniline hydroxylase in 500 mg/kg treated group were gradually decreased from 4 weeks after treated groups. In consequence it would sugested that the toxic effect of MGK-264 was low but in could offer hazard effect in liver and nervers system of rats if it was administrated move dose of MGK-264 and agumented in number of treated time.

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Thiobenzamide S-oxidation in Perfused Rat Liver: Ex Vivo Determination of Hepatic Flavin-Containing Monooxygenase Activity

  • Chung, Woon-Gye;Roh, Hyung-Keun;Cha, Young-Nam
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권5호
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    • pp.591-595
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    • 1997
  • An ex vivo assay determining the flavin-containing monooxygenase (FMO) activity in perfused rat liver has been developed by assessing the rate of thiobenzamide S-oxide (TBSO) formation from the infused thiobenzamide (TB). The hepatotoxicity by TB or TBSO was not a critical factor for maintaining the FMO activity for up to 50 min. The FMO activity expressed in nmoles TBSO produced/g liver/min was the same for the recycling and non-recycling perfusion. This implies that reduction of the oxidized TBSO back to the parent compound (TB) is negligible. Hydrolysis of the collected perfusates with either ${\beta}-glucuronidase$ or arylsulfatase did not increase the TBSO level and thus, TBSO does not appear to undergo conjugation either to glucuronide or sulfate esters. Thus, measuring the rate of TB S-oxidation in the isolated perfused liver with 1 mM TB for 50 min provides a useful tool for evaluation of the hepatic FMO activity in the absence of hepatic necrosis and without the interferences caused by further conjugation or back reduction of the TBSO to the parent TB.

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