RGD Reference Report - Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system. - Rat Genome Database

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Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system.

Authors: Rybak, LP  Husain, K  Whitworth, C  Somani, SM 
Citation: Rybak LP, etal., Toxicol Sci. 1999 Feb;47(2):195-202.
RGD ID: 9197256
Pubmed: PMID:10220857   (View Abstract at PubMed)

This study investigated the alterations that occur in auditory brainstem-evoked responses (ABRs) concurrent with changes in cochlear concentrations of glutathione (GSH), lipid peroxidation, and antioxidant enzyme activity in cisplatin-induced ototoxicity and in dose-dependent otoprotection by an antioxidant lipoate. Male Wistar rats were divided into different groups and were treated as follows, with: (1) vehicle (saline) control; (2) cisplatin (16 mg/kg, i.p.); (3) lipoate (100 mg/kg, i.p.) plus saline; (4) cisplatin plus lipoate (25 mg/kg); (5) cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus lipoate (100 mg/kg). Post-treatment ABRs were evaluated after three days, the rats were sacrificed, and cochleae were harvested and analyzed. The cisplatin-injected rats showed ABR threshold elevations above the pre-treatment thresholds. Rats treated with lipoate plus cisplatin did not show significant elevation of hearing thresholds. Cisplatin administration resulted in a depletion of cochlear GSH concentration (69% of control), whereas, cisplatin-plus-lipoate treatment increased GSH concentration close to control value. Cisplatin-treated rats showed a decrease in cochlear superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities (57, 78, 59, and 58% of control, respectively), and an increase in malondialdehyde (MDA) concentration (196% of control). Cochlear SOD, CAT, GSH-Px, and GR activities and MDA concentrations were restored in the rats injected with cisplatin plus graded doses of lipoate than those with cisplatin alone. It is concluded that cisplatin-induced ototoxicity is related to impairment of the cochlear antioxidant defense system, and the dose-dependent otoprotection conferred by an antioxidant lipoate against cisplatin ototoxicity is associated with sparing of the cochlear antioxidant defense system.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CATHumanHearing Loss, Cisplatin-Induced  ISOCat (Rattus norvegicus)protein:decreased expression:cochlear:RGD 
CatRatHearing Loss, Cisplatin-Induced  IEP protein:decreased expression:cochlear:RGD 
CatMouseHearing Loss, Cisplatin-Induced  ISOCat (Rattus norvegicus)protein:decreased expression:cochlear:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cat  (catalase)

Genes (Mus musculus)
Cat  (catalase)

Genes (Homo sapiens)
CAT  (catalase)


Additional Information