Document Detail

Cisplatin ototoxicity and the possibly protective effect of alpha-melanocyte stimulating hormone.
MedLine Citation:
PMID:  10082280     Owner:  NLM     Status:  MEDLINE    
It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so-called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our group has found that cisplatin-induced ototoxicity can also be reduced or prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766 (Hamers et al., 1994; De Groot et al., 1997). The present study was designed to investigate the possibly ameliorating effects of the physiologically more relevant naturally occurring neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) upon cisplatin ototoxicity and to compare its protective effects to those of ORG 2766. For eight consecutive days guinea pigs were treated with cisplatin at a concentration of either 1.5 mg/kg/day or 2 mg/kg/day. Animals were co-treated with either alpha-MSH (75 microg/kg/day), ORG 2766 (75 microg/kg/day), or a sham injection containing physiological saline. Electrocochleography and hair cell counts were performed. Treatment with 1.5 mg/kg/day cisplatin resulted in a large variability of the morphological and electrophysiological data, a variability that might have masked possible effects of ORG 2766 and alpha-MSH. Treatment with 2 mg/kg/day cisplatin caused less variable, severe reductions in the compound action potentials and cochlear microphonics combined with basal and middle-turn outer hair cell loss in five out of six animals. However, in the alpha-MSH co-treated groups, two out of six animals could be classified as normal, two animals as moderately affected and two animals as severely affected. In the ORG 2766 co-treated group we found three animals that were not affected and three animals that were severely affected. We conclude that the protective effects of alpha-MSH and ORG 2766 co-treatment are comparable and that alpha-MSH might be clinically useful in protecting against cisplatin-induced ototoxicity.
P S Heijmen; S F Klis; J C De Groot; G F Smoorenburg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hearing research     Volume:  128     ISSN:  0378-5955     ISO Abbreviation:  Hear. Res.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-04-27     Completed Date:  1999-04-27     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7900445     Medline TA:  Hear Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  27-39     Citation Subset:  IM    
Department of Otorhinolaryngology, University Hospital Utrecht, The Netherlands.
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MeSH Terms
Action Potentials / drug effects
Adrenocorticotropic Hormone / analogs & derivatives,  pharmacology
Cell Survival / drug effects
Cisplatin / antagonists & inhibitors*,  poisoning*
Cochlear Microphonic Potentials / drug effects
Ear, Inner / drug effects*,  pathology,  physiopathology
Guinea Pigs
Hair Cells, Auditory, Inner / drug effects,  pathology
Hair Cells, Auditory, Outer / drug effects,  pathology
Peptide Fragments / pharmacology
alpha-MSH / pharmacology*
Reg. No./Substance:
0/Peptide Fragments; 15663-27-1/Cisplatin; 50913-82-1/Org 2766; 581-05-5/alpha-MSH; 9002-60-2/Adrenocorticotropic Hormone

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