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Titolo:
Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: Antioxidant defense system
Autore:
Rybak, LP; Husain, K; Whitworth, C; Somani, SM;
Indirizzi:
So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA So Illinois Univ Springfield IL USA 62794 acol, Springfield, IL 62794 USA So Illinois Univ, Sch Med, Dept Surg, Springfield, IL 62794 USA So Illinois Univ Springfield IL USA 62794 Surg, Springfield, IL 62794 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 2, volume: 47, anno: 1999,
pagine: 195 - 202
SICI:
1096-6080(199902)47:2<195:DDPBLA>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
RENAL CORTICAL SLICES; OUTER HAIR CELL; 4-METHYLTHIOBENZOIC ACID; SODIUM THIOSULFATE; GLUTATHIONE-PEROXIDASE; INDUCED NEPHROTOXICITY; SUPEROXIDE-DISMUTASE; REDUCED GLUTATHIONE; ANTITUMOR-ACTIVITY; FREE-RADICALS;
Keywords:
cisplatin; ototoxicity; antioxidant enzyme; glutathione; lipoate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Somani, SM So Illinois Univ, Sch Med, Dept Pharmacol, POB 19230, Springfield, IL 62794 USA So Illinois Univ POB 19230 Springfield IL USA 62794 L 62794 USA
Citazione:
L.P. Rybak et al., "Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: Antioxidant defense system", TOXICOL SCI, 47(2), 1999, pp. 195-202

Abstract

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 incisplatin-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, ip); (3) lipoate (100 mg/kg, ip) plus saline; (4) cisplatin pluslipoate (25 mg/kg); (5) cisplatin plus lipoate (50 mg/kg), and (6) cisplatin plus lipoate (100 mg/kg). Post-treatment ABRs were evaluated after threedays, 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 cochlearantioxidant defense system.

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Documento generato il 05/07/20 alle ore 01:01:18