Volume 18 Issue 3
Jun.  2005
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KAZIM HUSAIN, CRAIG WHITWORTH, SATU M. SOMANI, LEONARD P. RYBAK. Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats[J]. Biomedical and Environmental Sciences, 2005, 18(3): 198-206.
Citation: KAZIM HUSAIN, CRAIG WHITWORTH, SATU M. SOMANI, LEONARD P. RYBAK. Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats[J]. Biomedical and Environmental Sciences, 2005, 18(3): 198-206.

Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats

Funds:  This work was supported in part by the Central Research Committee (CRC) Grant of SIU School of Medicine
  • 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.
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Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats

Funds:  This work was supported in part by the Central Research Committee (CRC) Grant of SIU School of Medicine

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.

KAZIM HUSAIN, CRAIG WHITWORTH, SATU M. SOMANI, LEONARD P. RYBAK. Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats[J]. Biomedical and Environmental Sciences, 2005, 18(3): 198-206.
Citation: KAZIM HUSAIN, CRAIG WHITWORTH, SATU M. SOMANI, LEONARD P. RYBAK. Partial Protection by Lipoic Acid Against Carboplantin-induced Ototoxicity in Rats[J]. Biomedical and Environmental Sciences, 2005, 18(3): 198-206.

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