Protective Effect of N-Acyl Amino Acids (NAAs) on Cephaloridine (CER) Nephrotoxicity in Rabbits.

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  • Hirouchi Yasukuni
    Product Development Laboratories, Sankyo Co., Ltd.
  • Naganuma Hideo
    Product Development Laboratories, Sankyo Co., Ltd.
  • Kawahara Yukinori
    Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd.
  • Okada Ryuzo
    Product Development Laboratories, Sankyo Co., Ltd.
  • Kamiya Akira
    Department of Hospital Pharmacy, School of Medicine, Yamaguchi University
  • Inui Ken-ichi
    Department of Hospital Pharmacy, School of Medicine, Tokyo Medical and Dental University
  • Hori Ryohei
    Department of Hospital Pharmacy, Faculty of Medicine, Kyoto University

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The protective effect of N-acyl amino acids (NAAs) against cephaloridine (CER)-induced nephrotoxicity was studied in rabbits. A large single intravenous dose of CER (more than 100 mg/kg) induced severe proximal tubular necrosis. Simultaneous treatment with several NAAs (at dosages of 100, 200 mg/kg, etc., i.v.), such as N-benzoyl-β-alanine (NBBA), N-benzoyl-6-aminocaproic acid, and Nα, ε-dibenzoyl-D, L-lysine, remarkably suppressed the histopathological damage in the kidney induced by CER. NAAs have generally low toxicity in laboratory animals (e.g., the LD50 of NBBA was more than 3, 000 mg/kg, i.v. in rats), and NAAs were suggested to be good candidates for reducing the nephrotoxicity of CER and other β-lactam antibiotics.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 63 (4), 487-493, 1993

    公益社団法人 日本薬理学会

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