EFFECTS OF FOSFOMYCIN CALCIUM AND SODIUM SALTS ON THE VISUAL AND AUDITORY ORGANS

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  • Fosfomycinの視覚および聴覚器におよぼす影響
  • Fosfomycin ノ シカク オヨビ チョウカクキ ニ オヨボス エイキョ

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Abstract

Fosfomycin (FOM), a new antibiotic having a broad-spectrum, was isolated from Streptomyces fradiae, S. viridochromogenes and S. wedmorensis. Its action is bactericidal and involves interference with cell wall synthesis as evidence by the fact that it causes spheroplast formation by susceptible bacteria.<BR>In this work, we studied about toxicological effects of FOM on the visual and auditory organs of Hartley strain guinea pigs, rabbits and beagle dogs.<BR>FOM-Ca salt was suspended with 0.1% CMC and FOM-Na salt was disolved into the distilled water.<BR>A. FOM-Ca<BR>FOM-Ca at the doses of 200 and 400mg/kg were orally administered to rabbits for 35 days exceptevery Sunday and after the treatment effects of FOM-Ca on the electroretinogram (ERG) of the rabbits. The light stimulation of 2 joules was given at 50cm from rabbits eyes and then ERG was measured at 1, 18 and 35 days after the application of the drug. There was no remarkable difference between the treatment and control groups during the experiments.<BR>In second experiments, effects of the drug on the optic fundus of Beagle dogs were also studied. FOM-Ca at the dose of 560mg/kg was orally administered for 35 days to examine by a camera (RC-2) made by Kowa Kogyo. There was also no remarkable difference between the treated and control groups during experiments.<BR>In third experiments, the ototoxic effects of FOM-Ca on the inner ear of guinea pigs, were studied.<BR>FOM-Ca at the doses of 250,500 and 750mg/kg were given by subcutaneous injections for 28 days respectively. After the last administration, we studied the ototoxic effects with following methods.<BR>(a) Succinic dehydrogenase (SDH) activity: The organs of CORTI were soaked in intravital perfusion of 0.1% NBT solution for 15 minutes. After 24 hours of fixation with 10% neutral formalin, the surface preparation specimens were prepared under the stereomicroscope. After that, SDH activities of outer and inner hair cells of organs of CORTI were estimated by observation under the light microscope.<BR>(b) Pathological examination of organ of CORTI: The specimen obtained from organ of CORTI were fixed with WITTMAACK solution and we prepared the serial celloidin horizontal section and stained with hematoxylin-eosin. And then, the outer hair cells and inner hair cells of organ of CORTI were observed under the light microscope.<BR>There was no remarkable difference between the treated and control groups by these treatments.<BR>B. FOM-Na<BR>FOM-Na at the doses 100 and 400mg/kg were intravenously administered to rabbits and Beagle dogs was given 500mg/kg for 35 days except every Sunday. After these treatments, the ERG of rabbits and optic fundus of Beagle dogs were examined. There was no remarkable difference between the treated and control groups during the experiments.<BR>In other experiments, the ototoxic effects of FOM-Na on the inner ear of guinea pigs were studied.<BR>FOM-Na at the doses of 200, 400 and 800mg/kg were intramuscularly given for 28 days respectively. After the last administration, the ototoxic effects of the drug were examined by the established method.<BR>There was no remarkable difference in all animals used in this work.

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