Cisplatin ototoxicity. An electrophysiological dose-effect study in albino guinea pigs. 1998

C H Stengs, and S F Klis, and E H Huizing, and G F Smoorenburg
Department of Otorhinolaryngology, University Hospital Utrecht, The Netherlands.

Recently, the effect of the ACTH(4-9) analog, ORG2766, on cisplatin ototoxicity was studied by Hamers et al. (1994). This study showed that the ACTH(4-9) analog partially prevents the ototoxicity of cisplatin. The authors suggested that the daily dose of 2.0 mg/kg/day for 8 days might have been too high to obtain full protection. Knowledge about dose-effect relations for cisplatin ototoxicity is rather meager. Therefore, we conducted a basic dose-effect study for cisplatin without any concomitant additives. A follow-up of the Hamers et al. (1994) study, based on dose-effect data from this paper, is presented in a companion paper. The effects of cisplatin on the compound action potential (CAP), cochlear microphonics (CM) and summating potential (SP) were determined in acute experiments, in different groups of albino guinea pigs, each group injected with a different dose of cisplatin. Daily doses ranged from 0.7 to 2.0 mg/kg/day cisplatin (i.p.) for 8 consecutive days. Electrocochleography was performed at day 10. The measurements were performed over a broad range of frequencies (0.5-16 kHz). The results showed clustering of the data in two groups, the first group concerning the treatments of 1.5 and 2.0 mg/kg/day with large frequency-dependent losses in the three cochlear potentials, the second group concerning the treatments with lower doses of cisplatin (0.7, 1.0 and 1.25 mg/kg/day) where almost no losses in the three cochlear potentials were found. The threshold curves regarding the lower doses (0.7-1.25 mg/kg/day) were almost indistinguishable from the control threshold curve except at the higher frequencies (12 and 16 kHz). Thus, a marked transition from almost no ototoxic effect to a large effect seems to occur between cisplatin doses of 1.25 and 1.5 mg/kg/day for 8 days. The small difference between the effects found for 1.5 mg/kg/day and 2 mg/kg/day suggests that a smaller dose than the one of 2 mg/kg/day for 8 days used previously (Hamers et al., 1994) might better suit research into protection against cisplatin ototoxicity.

UI MeSH Term Description Entries
D007758 Ear, Inner The essential part of the hearing organ consists of two labyrinthine compartments: the bony labyrinthine and the membranous labyrinth. The bony labyrinth is a complex of three interconnecting cavities or spaces (COCHLEA; VESTIBULAR LABYRINTH; and SEMICIRCULAR CANALS) in the TEMPORAL BONE. Within the bony labyrinth lies the membranous labyrinth which is a complex of sacs and tubules (COCHLEAR DUCT; SACCULE AND UTRICLE; and SEMICIRCULAR DUCTS) forming a continuous space enclosed by EPITHELIUM and connective tissue. These spaces are filled with LABYRINTHINE FLUIDS of various compositions. Labyrinth,Bony Labyrinth,Ear, Internal,Inner Ear,Membranous Labyrinth,Bony Labyrinths,Ears, Inner,Ears, Internal,Inner Ears,Internal Ear,Internal Ears,Labyrinth, Bony,Labyrinth, Membranous,Labyrinths,Labyrinths, Bony,Labyrinths, Membranous,Membranous Labyrinths
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
D003055 Cochlear Microphonic Potentials The electric response of the cochlear hair cells to acoustic stimulation. Cochlear Microphonic Potential,Potential, Cochlear Microphonic,Potentials, Cochlear Microphonic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D005260 Female Females
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
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
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy

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