Biomaterial Database

Mechanism of protection by diethyldithiocarbamate against cisplatin ototoxicity: antioxidant system. 1995

L P Rybak, and R Ravi, and S M Somani

Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794-9230, USA.

This investigation was undertaken to explain the possible, mechanism(s) of protection by diethyldithiocarbamate (DDTC) against cisplatin ototoxicity. Male Wistar rats (250-275 g) underwent pretreatment auditory brain stem-evoked responses (ABRs). The different groups of rats were injected as follows: (1) cisplatin (16 mg/kg i.p.), (2) cisplatin plus DDTC (16 mg/kg i.p. + 600 mg/kg, s.c.), and (3) control rats. Post-treatment ABRs were performed after 3 days and the rats were euthanized and cochleae were harvested. The cochleae were analyzed for glutathione (GSH) and oxidized glutathione, by HPLC, and for the activities of the antioxidant enzymes, and malondialdehyde levels, by spectrophotometry. The cisplatin-injected rats showed a threshold elevation of 36 +/- 3.05 dB above the pretreatment thresholds using click stimulus. Rats treated with cisplatin and then DDTC did not show a significant elevation of hearing threshold. DDTC-mediated protection was associated with higher levels of GSH (0.81 +/- 0.11 nmol/mg tissue), compared to 0.45 +/- 0.02 nmol/mg tissue following administration of cisplatin alone. Administration of cisplatin + DDTC restored the cochlear GSH-Px activity to control level. Cisplatin-treated rats were found to have decreased GSH-Px activity (75% of control). Cochlear SOD and CAT activities and MDA levels showed a decreasing trend in the animals injected with cisplatin + DDTC, compared to cisplatin-alone-treated rats. These data suggest that the protection conferred by DDTC against cisplatin ototoxicity is associated with sparing of the cochlear GSH/GSH-Px.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D002945	Cisplatin	An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.	Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D003051	Cochlea	The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH.	Cochleas
D004050	Ditiocarb	A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.	Diethyldithiocarbamate,Diethylcarbamodithioic Acid,Diethyldithiocarbamic Acid,Dithiocarb,Ditiocarb Sodium,Ditiocarb, Ammonium Salt,Ditiocarb, Bismuth Salt,Ditiocarb, Lead Salt,Ditiocarb, Potassium Salt,Ditiocarb, Sodium Salt,Ditiocarb, Sodium Salt, Trihydrate,Ditiocarb, Tin(4+) Salt,Ditiocarb, Zinc Salt,Imuthiol,Sodium Diethyldithiocarbamate,Thiocarb,Zinc Diethyldithiocarbamate,Ammonium Salt Ditiocarb,Bismuth Salt Ditiocarb,Diethyldithiocarbamate, Sodium,Diethyldithiocarbamate, Zinc,Lead Salt Ditiocarb,Potassium Salt Ditiocarb,Sodium Salt Ditiocarb,Sodium, Ditiocarb,Zinc Salt Ditiocarb
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D005979	Glutathione Peroxidase	An enzyme catalyzing the oxidation of 2 moles of GLUTATHIONE in the presence of HYDROGEN PEROXIDE to yield oxidized glutathione and water.	Cytosolic Glutathione Peroxidase,Glutathione Lipoperoxidase,Selenoglutathione Peroxidase,Glutathione Peroxidase, Cytosolic,Lipoperoxidase, Glutathione,Peroxidase, Glutathione,Peroxidase, Selenoglutathione
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000975	Antioxidants	Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.	Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D016057	Evoked Potentials, Auditory, Brain Stem	Electrical waves in the CEREBRAL CORTEX generated by BRAIN STEM structures in response to auditory click stimuli. These are found to be abnormal in many patients with CEREBELLOPONTINE ANGLE lesions, MULTIPLE SCLEROSIS, or other DEMYELINATING DISEASES.	Acoustic Evoked Brain Stem Potentials,Auditory Brain Stem Evoked Responses,Brain Stem Auditory Evoked Potentials,Evoked Responses, Auditory, Brain Stem,Acoustic Evoked Brain Stem Potential,Acoustic Evoked Brainstem Potential,Acoustic Evoked Brainstem Potentials,Auditory Brain Stem Evoked Response,Auditory Brain Stem Response,Auditory Brain Stem Responses,Auditory Brainstem Evoked Response,Auditory Brainstem Evoked Responses,Auditory Brainstem Responses,Brain Stem Auditory Evoked Potential,Brainstem Auditory Evoked Potential,Brainstem Auditory Evoked Potentials,Evoked Potential, Auditory, Brainstem,Evoked Potentials, Auditory, Brainstem,Evoked Response, Auditory, Brain Stem,Evoked Response, Auditory, Brainstem,Evoked Responses, Auditory, Brainstem,Auditory Brainstem Response,Brainstem Response, Auditory,Brainstem Responses, Auditory,Response, Auditory Brainstem,Responses, Auditory Brainstem
D017208	Rats, Wistar	A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.	Wistar Rat,Rat, Wistar,Wistar Rats