This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Husain, K. Articles by Rybak, L. Search for Related Content PubMed PubMed Citation Articles by Husain, K. Articles by Rybak, L. Social Bookmarking                         What's this?

Carboplatin-Induced Oxidative Injury in Rat Inferior Colliculus

Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA

Craig Whitworth

Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA

Stephen Hazelrigg

Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA

Leonard Rybak

Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in ototoxicity in cancer patients. Carboplatin-induced ototoxicity was related to oxidative stress to the cochlea and inner hair cell loss in animals. It is likely that initial oxidative injury spreads throughout the neuroaxis of the auditory system later. The study aim was to evaluate carboplatin-induced hearing loss and oxidative injury to the central auditory system (inferior colliculus) of the rat. Male Wistar rats were divided into two groups of seven animals each and treated as follows: (1) control (normal saline, intraperitoneal [IP]) and (2) carboplatin (256 mg/kg, IP). Auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the 4th day and inferior colliculus from brain stem and cerebellum were isolated and analyzed. Carboplatin significantly elevated the hearing threshold shifts at clicks, 2-, 4-, 8-, 16-, and 32-k Hz tone burst stimuli. Carboplatin significantly increased nitric oxide and lipid peroxidation, xanthine oxidase, and manganese superoxide dismutase activities in the inferior colliculus, but not in the cerebellum, indicating an enhanced flux of free radicals in the central auditory system. Carboplatin significantly depressed the reduced to oxidized glutathione ratio, antioxidant enzyme activities, such as copper-zinc superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and enzyme protein expressions in the inferior colliculus, but not in the cerebellum, 4 days after treatment. The data suggest that carboplatin induced oxidative injury specifically in the inferior colliculus of the rat leading to hearing loss.

Key Words: Antioxidants • Carboplatin • Inferior Colliculus • Lipid Peroxidation • Oxidative Injury

International Journal of Toxicology, Vol. 22, No. 5, 335-342 (2003)
DOI: 10.1177/109158180302200502


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. P. Carey, T. Cooper, G. I. Jallo, B. S. Carson Sr., and M. Guarnieri Ototoxicity of Carboplatin Delivered Locally in a Monkey Brainstem International Journal of Toxicology, November 1, 2005; 24(6): 443 - 449. [Abstract] [Full Text] [PDF]

				B. J. May, M. Guarnieri, B. S. Carson Sr, A. Bachani, and G. I. Jallo Long-term Effects of Carboplatin Brainstem Infusions on Hearing Thresholds in Monkeys Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1411 - 1415. [Abstract] [Full Text] [PDF]