Toxicological Sciences, Vol 47, 195-202, Copyright © 1999 by Society of Toxicology
LP Rybak, K Husain, C Whitworth and SM Somani
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.
ARTICLES
Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794, USA.
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