OBJECTIVETo investigate the alterations in auditory brainstem evoked responses (ABRs) and the changes of carboplatin-induced ototoxicity in the cochlear oxidant/antioxidant systems and otoprotection by an antioxidant lipoate.

METHODSMale wistar rats were divided into four groups and treated as follows: 1) vehicle (saline) control, 2) carboplatin (256 mg/kg, i.p.), 3) lipoate (100 mg/kg, i.p.), 4) lipoate + carboplatin. Post-treatment ABRs were performed after four days and rats were sacrificed with their cochleae harvested and analyzed.

RESULTSCarboplatin significantly elevated ABR threshold above the pretreatment thresholds. Lipoate+carboplatin treated rats showed decreased elevation of hearing threshold. Carboplatin significantly depleted cochlear reduced to oxizized glutathione (GSH/GSSG) ratio, whereas lipoate+carboplatin treatment increased GSH/GSSG ratio. Carboplatin significantly decreased cochlear copper zinc-superoxide dismutase (CuZn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR) and glutathione-S-transferase (GST) activities and enzyme protein expressions and a significant increase in Mn-SOD activity, protein expression and malondialdehyde (MDA) level. Cochlear antioxidant enzyme activities, enzyme protein expressions and MDA level were partially restored in lipoate+carboplatin treated rats, compared to carboplatin alone.

CONCLUSIONCarboplatin-induced ototoxicity is related to impairment of cochlear antioxidant system and otoprotection conferred by lipoate is associated with partial sparing of the cochlear antioxidant defense system.

Animals ; Antioxidants ; pharmacology ; Auditory Threshold ; drug effects ; Carboplatin ; Catalase ; metabolism ; Cochlea ; drug effects ; enzymology ; metabolism ; Evoked Potentials, Auditory, Brain Stem ; drug effects ; Glutathione ; metabolism ; Glutathione Disulfide ; metabolism ; Glutathione Peroxidase ; metabolism ; Glutathione Reductase ; metabolism ; Glutathione Transferase ; metabolism ; Hearing Loss, Sensorineural ; chemically induced ; Lipid Peroxidation ; Male ; Malondialdehyde ; metabolism ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Thioctic Acid ; pharmacology