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Titolo:
Round window membrane delivery of L-methionine provides protection from cisplatin ototoxicity without compromising chemotherapeutic efficacy
Autore:
Li, GM; Frenz, DA; Brahmblatt, S; Feghali, JG; Ruben, RJ; Berggren, D; Arezzo, J; Van de Water, TR;
Indirizzi:
Albert Einstein Coll Med, Dept Otolaryngol, Bronx, NY 10467 USA Albert Einstein Coll Med Bronx NY USA 10467 laryngol, Bronx, NY 10467 USA Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA Albert Einstein Coll Med Bronx NY USA 10467 uct Biol, Bronx, NY 10467 USA Albert Einstein Coll Med, Beth Israel Med Ctr, Dept Otolaryngol, Bronx, NY10467 USA Albert Einstein Coll Med Bronx NY USA 10467 olaryngol, Bronx, NY10467 USA Umea Univ, Dept Otolaryngol, Umea, Sweden Umea Univ Umea SwedenUmea Univ, Dept Otolaryngol, Umea, Sweden Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA Yeshiva Univ Albert Einstein Coll Med Bronx NY USA 10461 nx, NY 10461 USA
Titolo Testata:
NEUROTOXICOLOGY
fascicolo: 2, volume: 22, anno: 2001,
pagine: 163 - 176
SICI:
0161-813X(200104)22:2<163:RWMDOL>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CIS-PLATINUM NEPHROTOXICITY; AUDITORY HAIR-CELLS; OVARIAN-CANCER; INDUCED DAMAGE; INNER-EAR; IN-VITRO; DIAMMINEDICHLOROPLATINUM; NEURONS;
Keywords:
cisplatin ototoxicity; otoprotection; round window membrane delivery; chemotherapeutic efficacy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Van de Water, TR Albert Einstein Coll Med, Dept Otolaryngol, 1410 Pelham Pkwy S Kennedy Ctr,Room 302, Bronx, NY 10467 USA Albert Einstein Coll Med 1410 Pelham Pkwy S Kennedy Ctr,Room 302 Bronx NY USA 10467
Citazione:
G.M. Li et al., "Round window membrane delivery of L-methionine provides protection from cisplatin ototoxicity without compromising chemotherapeutic efficacy", NEUROTOXICO, 22(2), 2001, pp. 163-176

Abstract

Cisplatin (cis-diamminedichloroplatinum(II) (CDDP)) is a widely used highly effective, oncolytic agent that has serious ototoxic side-effects. To rest the effectiveness of local delivery of L-methionine (L-Met) as nit otoprotective agent against CDDP otoroxicity we used a rat model of a highly metastatic breast cancer tumor i.e. Fisher 344 mts implanted with MTLn3 breast cancer cells. Four experimental groups were evaluated - I: untreated; II: CDDP-treated (three dosages); III: systemically-delivered L-Met + CDDP-treated; IV: locally delivered L-Met + CDDP-treated. The integrity of the outer hair cells (OHCs) was determined using scanning electron microscopy (SEM); hearing was assessed by recording auditory brainstem responses (ABRs) at multiple frequencies. The chemotherapeutic effectiveness of CDDP was quantified by measuring changes in tumor mass and the presence of tumor metastasis. L-Met provided otoprotection of the OHCs against CDDP toxicity in the cochleae of rats following either systemic (III) or local (IV) administration. The ABRs were unchanged in each of the L-Met protection Groups (III and IV)and in the untreated animals of Group I. Treatment with CDDP only (II) induced significant hearing losses at both 16 and Ig kHz when compared to ABRsof untreated mls(lj. CDDP was effective in controlling the MTLn3 initiatedbreast cancer tumors iii the CDDP-treated (II) and the local L-Met protection, CDDP-treated (IV) Groups. In contrast, the tumors in the systemic L-Met protection, CDDP-treated Group (III) were not controlled by the CDDP treatment regime. This study demonstrates that local delivery of L-Met to the scala tympani of the cochlea via the round window membrane (Nj provides effective protection against CDDP ototoxicity without compromising its ability to control a highly metastatic form of cancer: (C) 2001 Elsevier Science Inc. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/05/20 alle ore 19:57:26