TOXICITY TESTS OF T-1982 (VI) Influence of T-1982 in combination with furosemide on the kidney

• Published in: CHEMOTHERAPY Vol. 30; no. Supplement3; pp. 345 - 358
• Main Authors: NAKAGAWA, SHIGEHITO, SHIBATA, TETSUO, SATO, SHIGERU, NAGAI, AKIO, INABA, JUNKO, YONEDA, TOYOAKI, TAKAI, AKIRA
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 25-12-1982
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.30.Supplement3_345

T-1982, a newly developed cephamycin antibiotic, was injected intravenously at dose levels of 250mg/kg and 1000mg/kg to rats which were pretreated by glycerol (4 ml/kg, s. c.) and furosemide (50mg/kg, s. c.). At 24 hrs after treatment, the influcence of T-1982 on the kidney was examined in comparison with CET and CEZ by the urinalysis, the plasma urea nitrogen and creatinine and the renal morphological observations. In addition, T-1982 at 1000mg/kg was given alone or in combination with furosemide (s. c.) to rats intravenously. The following results were obtained. 1) Renal damage was seen neither in rats given T-1982 at 1000mg/kg alone nor in rats given T-1982 at 1000mg/kg+F. 2) Renal damage was severer in rats given T-1982 at 250 or 1000mg/kg in combination with G+ F. This tendency was clearer at the high dose level. 3) Toxic signs of the above renal damage was shown by the following observations; proteinuria, elevation of the plasma urea nitrogen and creatinine, necrosis of the renal tubular epithelium in micro scopic findings and degenerative or necrotic changes of the proximal tubular epithelial cells in electronmicroscopy. 4) Similar stretched renal damage was revealed by an additional injection of CET or CEZ to G+F pretreated rats. 5) In this experiment, the influence on die kidney appeared to be CET≅CEZ≥T-1982.