High concentrations of thiosulfate in scala tympani perilymph after systemic administration in the guinea pig.
CONCLUSIONS
High concentrations of the antioxidant thiosulfate reach scala tympani perilymph after i.v. administration in the guinea pig. Thiosulfate concentrations in perilymph remain elevated longer than in blood. This warrants further studies on the possibility of obtaining otoprotection by thiosulfate administration several hours before that of cisplatin without compromising the anticancer effect caused by cisplatin inactivation in the blood compartment.


OBJECTIVE
Thiosulfate may reduce cisplatin-induced ototoxicity, presumably by oxidative stress relief and formation of inactivate platinum complexes. This study aimed to explore to what extent thiosulfate reaches scala tympani perilymph after systemic administration in the guinea pig.


METHODS
Scala tympani perilymph (1 microl) was aspirated from the basal turn of each cochlea up to 3 h after thiosulfate administration (103 mg/kg b.w., i.v.). Blood samples were also taken. Thiosulfate was quantified by HPLC and fluorescence detection.


RESULTS
Substantial thiosulfate concentrations were found in perilymph. The area under the concentration-time curve for thiosulfate in perilymph and blood was 3100 microMxmin and 6300 microMxmin, respectively. The highest thiosulfate concentrations in perilymph were found at the first sampling at about 10 min. Due to a more rapid elimination from blood, perilymph concentrations exceeded those of blood towards the end of the experiment.
Pierre
Pernilla Videhult
PV
Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. pernilla.videhult-pierre@apoteket.se
Engmér
Cecilia
C
Wallin
Inger
I
Laurell
Göran
G
Ehrsson
Hans
H
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010498:Perilymph / Q000378:metabolism*; D012533:Scala Tympani / Q000378:metabolism*; D013885:Thiosulfates / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000975:Antioxidants; D013885:Thiosulfates; C017717:sodium thiosulfate