Summary
Whether an active accumulation of ototoxic substances or their metabolites occurs in the cochlea, or whether there exists a delayed elimination of these products from the endo- and perilymphatic fluids, following a passive equilibrium between the blood and the body tissues, is still a subject for discussion.
To investigate the cochlear distribution of an ototoxic substance and its elimination rate, compared to other organs in the body, atoxyl, with known ototoxic effects (Anniko and Wersäll, 1975a, b; Anniko, 1976a, b) was used as a test substance. The neutron activation analysis technique was used to measure the atoxyl concentration in various parts of the body (cochlea, blood, muscle, kidney and cortical femoral bone) after various lengths of time following a subcutaneous injection of 100 mg/kg b.w. of atoxyl.
Atoxyl was retained in the cochlea for a long period and a delayed elimination occurred from the inner ear. The excretion of atoxyl was likely to appear via the kidneys.
Zusammenfassung
Es wird noch diskutiert ob eine aktive Akkumulation ototoxischer Substanzen oder ihrer Metaboliten in der Cochlea vorkommt, oder, wenn eine verzögerte Elimination dieser Produkte einem passiven Equilibrium zwischen Blut und Körpergeweben folgend auftritt, ob sie von den endo- und perilymphatischen Flüssigkeiten herrührt.
Um die cochleäre Distribution einer ototoxischen Substanz und ihren Eliminationsgrad im Verhältnis zu anderen Organen des Körpers zu untersuchen, wurde Atoxyl mit schon bekannten ototoxischen Effekten (Anniko und Wersäll, 1975a, b; Anniko, 1976a, b) als Testsubstanz angewandt. Man wandte die Aktivierungsanalysentechnik an um die Konzentration von Atoxyl in verschiedenen Teilen des Körpers (Cochlea, Blut, Muskeln, Nieren und dem corticalen Femur) nach divergierenden Zeitintervallen einer s.c. Injektion von 100 mg Atoxyl per kg Körpergewicht folgend, zu messen.
Atoxyl wurde für eine lange Zeit in der Cochlea behalten und wies einen verzögerten Eliminierungsgrad vom Innenohr auf. Die Ausscheidung von Atoxyl kam vorzugsweise durch die Nieren vor.
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Supported by grants from Karolinska Institutet, Stockholm, and the Swedish Medical Research Council (grant no. B76-12X)
The authors wish to express their appreciation to Professor Jan Wersäll for his never failing interest in this work and for his critical revision of the manuscript. The technical assistance of Mrs. Marie-Louise Spångberg, Miss Anne-Marie Lundberg and Mr. Bengt Hedberg is gratefully acknowledged. The manuscript was reviewed linguistically by Mrs. Ann Kempe.
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Anniko, M., Plantin, LO. Delayed elimination of the ototoxic compound atoxyl from the inner ear. Arch Otorhinolaryngol 215, 81–89 (1977). https://doi.org/10.1007/BF00463195
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DOI: https://doi.org/10.1007/BF00463195