title: Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Southern Illinois University, School of Medicine, Springfield, IL 62794, USA. khusain@psm.edu
authors.forename: Kazim
authors.initials: K
authors.lastname: Husain
authors.forename: Craig
authors.initials: C
authors.lastname: Whitworth
authors.forename: Satu M
authors.initials: SM
authors.lastname: Somani
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Rybak
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001309:Auditory Threshold / Q000187:drug effects; D016190:Carboplatin; D002374:Catalase / Q000378:metabolism; D003051:Cochlea / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D008315:Malondialdehyde; D008063:Thioctic Acid; D016190:Carboplatin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione; D019803:Glutathione Disulfide