Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats.
- Author:
Kazim HUSAIN
1
;
Craig WHITWORTH
;
Satu M SOMANI
;
Leonard P RYBAK
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Biomedical and Environmental Sciences 2005;18(3):198-206
- CountryChina
- Language:English
-
Abstract:
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.
