Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model.
Glutathione (GSH) provides an important antioxidant and detoxification pathway. We tested to determine if direct administration of GSH or GSH ester could reduce cisplatin- (CDDP) induced ototoxicity. We tested eight groups of five rats each: a control group, a group receiving 16 mg/kg ip CDDP infused over 30 minutes, and six groups receiving either GSH or GSH ester at 500, 1000, or 1500 mg/kg intraperitoneally 30 minutes prior to 16 mg/kg CDDP. Auditory brainstem response thresholds were measured for click and tone-burst stimuli at baseline and 3 days later. Outer hair cell (OHC) loss was measured for the apical, middle and basal turns. The 500 mg/kg GSH ester reduced hearing loss and OHC loss, but protection decreased as dosage increased, suggesting possible toxicity. GSH was not significantly protective. The best GSH ester protection was less than we have previously reported with D-methionine.
Campbell
Kathleen C M
KC
Southern Illinois University School of Medicine, Springfield, IL, USA. kcampbell@SIUmed.edu
Larsen
Deb L
DL
Meech
Robert P
RP
Rybak
Leonard P
LP
Hughes
Larry F
LF
D000161:Acoustic Stimulation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000648:ultrastructure; D034381:Hearing Loss / Q000139:chemically induced*; D008658:Inactivation, Metabolic; D007274:Injections, Intraperitoneal; D051381:Rats
D000970:Antineoplastic Agents; C008259:lauryl gallate; D005707:Gallic Acid; C042431:S-ethyl glutathione; D005978:Glutathione; D002945:Cisplatin