Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats.

Article Details

Citation

Husain K, Whitworth C, Somani SM, Rybak LP

Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats.

Biomed Environ Sci. 2005 Jun;18(3):198-206.

PubMed ID
16131024 [ View in PubMed
]
Abstract

OBJECTIVE: To 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. METHODS: Male 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. RESULTS: Carboplatin 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. CONCLUSION: Carboplatin-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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
CarboplatinSuperoxide dismutase [Cu-Zn]ProteinHumans
Unknown
Inhibitor
Details