EFFECTS OF METHYL (+) (3S)-1,2,3,4-TETRAHYDRO-3-HYDROXYMETHYL-β-CARBOLINE-2-CARBODITHIOATE (THC), A NEW HEPATOPROTECTIVE AGENT, ON ACUTE LIVER INJURIES INDUCED BY VARIOUS HEPATOTOXIC SUBSTANCES IN MICE AND RATS

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概要

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• The effects of oral administration of methyl (+) (3S)-1,2,3,4-tetrahydro-3-hydroxymethyl-β-carboline-2-carbodithioate (THC) on acute liver injuries induced by carbon tetrachloride (CCl_4), bromobenzene (B.B.), D-galactosamine (GALN) and α-naphthylisothio-cyanate (ANIT) in rats and allyl alcohol (A.A.) in mice were studied. THC suppressed the elevation of plasma transaminase activities and hepatic lipid contents induced by CCl_4 in rats when the animals were treated with THC for 4 consecutive days simultaneously with CCl_4 administration. THC also suppressed the elevation of hepatic lipid contents induced by the 4 d-treatment of rats with CCl_4 when administered for 4 consecutive days from the next day after treatment with CCl_4. This effect of THC was histopathologically confirmed. In addition, pretreatment with THC protected rats against liver injuries induced by B.B., GALN, and ANIT, but not against A.A. in mice. This protection was evident from the suppression of elevated activities of plasma transaminase and/or elevated contents of hepatic lipid induced by these hepatotoxic substances. Furthermore, THC inhibited the formation of lipid peroxide in rat liver microsomes with an IC_<50> of 3.2 μM. These results suggested that THC protected rats against liver injuries induced by CCl_4,B.B., GALN and ANIT and had a protective effect on the microsomal membrane against lipid peroxide in vitro.

• 公益社団法人日本薬学会の論文

著者

• Matsumoto M

  Osaka Medical Center For Cancer And Cardiovascular Diseases Osaka

• Matsumoto Misako

  Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases

• Matsumoto Mitsuharu

  Takeda Chemical Industries Ltd. Pharmaceutical Research Division

• Matsuoka Y

  Safety Research Laboratory And Organic Chemistry Research Laboratory Tanabe Seiyaku Co. Ltd.

• SAIGA Yutaka

  Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• IIJIMA Ikuo

  Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd.,

• Iijima I

  Lead Optimization Research Laboratory Tanabe Seiyaku Co. Ltd.

• Saiga Y

  Lead Optimization Research Laboratory Tanabe Seiyaku Co. Ltd.

• MATSUMOTO MAMORU

  Safety Research Laboratory

• MATSUOKA YUZO

  Safety Research Laboratory

• SAIGA YUTAKA

  Safety Research Laboratory

• IIJIMA IKUO

  Safety Research Laboratory

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