Inhibition of Hepatic Drug Biotransformation by Carrageenan-Induced Inflammation in the Rat : Effect of Sex Hormone Alterations

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概要

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• Following in vivo treatment with carrageenan, sex-related differences in alteration of hepatic drug metabolism were found in the rat. In adult male rats, marked decreases were observed in hepatic 9000×g supernatant cytochrome P-450 content and in the biotransformation of hexobarbital, aminopyrine, ethylmorphine, and meperidine. Hexobarbital hypnosis was significantly prolonged by carrageenan treatment in intact and testectomized animals as compared to their respective controls. Although carrageenan-treated intact animals slept 480% longer, carrageenan-treated testectomized rats slept only 60% longer than the respective control animals. However, testectomy or administration of 17β-estradiol to testectomized male rats did not inhibit the monooxygenase activities by carrageenan-treatment. Furthermore, administration of testosterone to ovariectomized female rats did not antagonize the inhibitory effects of the carrageenan-induced inflammation. The inhibitory effects produced by carrageenan-induced inflammation on the microsomal enzyme system were observed only in mature male rats and were not observed in mature female rats or in sexually immature rats of either sex. Thus, these results suggest that the inhibitory effects of carrageenan-induced inflammation on hepatic 9000×g supernatant monooxygenases in the male rat are partially mediated through the toxic action of carrageenan-induced inflammation on androgen-dependent factors in this enzyme system.

• 公益社団法人日本薬学会の論文

著者

• SASAKI Kenroh

  Department of Pharmacognosy, Tohoku Pharmaceutical University

• ISHIKAWA Masaaki

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical Universi

• Sasaki K

  Dep. Of Pharmacology And Toxicology Cancer Res. Inst. Tohoku Pharmaceutical Univ.

• TAKAYANAGI Yoshio

  Department of Pharmacology and Toxicology, Cancer Research Institite, Tohoku Phamaceutical Universit

• Ishikawa Masaaki

  東北薬科大学癌研究所

• Sasaki Kenichi

  Departments of Pathology, Kitasato University School of Medicine

• OZAKI Masayasu

  Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy

• Ishikawa Masaaki

  Department Of Clinical Pharmacotherapeutics Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Ishikawa Masaaki

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku College Of Pharmacy

• Takayanagi Y

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Sasaki Kenroh

  Department Of Pharmacognosy Tohoku Pharmaceutical University

• Ozaki Masayori

  Department Of Pharmacology 2:department Of Pathology 2 Nagasaki University School Of Medicine

• Ozaki Masayasu

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku College Of Pharmacy

• Kanno Shu-ichi

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Sasaki Ken-ichi

  Department Of Pharmacology And Toxicology Cancer Research Institute Tohoku Pharmaceutical University

• Sasaki Kenichi

  Department Of Cardiology Kitano Hospital Medical Research Institute

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