Carboplatin-induced oxidative injury in rat inferior colliculus.
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 [i.p.]) and (2) carboplatin (256 mg/kg, i.p.). 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-kHz 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.
Husain
Kazim
K
Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA. khusain@psm.edu
Whitworth
Craig
C
Hazelrigg
Stephen
S
Rybak
Leonard
L
D000161:Acoustic Stimulation; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D016190:Carboplatin / Q000633:toxicity*; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004566:Electrodes; D004797:Enzyme-Linked Immunosorbent Assay; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007245:Inferior Colliculi / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D008054:Lipid Peroxides; D009569:Nitric Oxide; D016190:Carboplatin; D005978:Glutathione; D019803:Glutathione Disulfide