Co-administration of the neurotrophic ACTH(4-9) analogue, ORG 2766, may reduce the cochleotoxic effects of cisplatin. 1997

J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
Department of Otorhinolaryngology, University Hospital Utrecht, The Netherlands. j.c.m.j.degroot@kmb.azu.nl

In this study the effect of the neurotrophic ACTH(4-9) analogue, ORG 2766, on cisplatin cochleotoxicity was investigated with both light- and transmission electron microscopy. Guinea pigs were treated with either cisplatin+ORG 2766 (n = 11) or cisplatin + physiological saline (n = 9). All animals treated with cisplatin + physiological saline showed complete loss of outer hair cells (OHC) and degeneration of the organ of Corti in the basal cochlear turns, while partial OHC loss was found in the middle and apical turns. The inner hair cells (IHC) and other cochlear tissues were not affected. Eight animals from the group treated with cisplatin + ORG 2766 demonstrated similar pathological changes, but to a lesser degree, especially in the middle turns. The three remaining animals demonstrated no cochlear alterations at all, light-microscopically, and only minor subcellular changes in the OHCs at the ultrastructural level. Electrophysiologically, these three animals showed normals compound action potential (CAP) amplitudes at stimulus frequencies from 0.5 to 16 kHz and normal cochlear microphonics (CM) in the frequency range from 0.5 to 8 kHz. The other animals treated with cisplatin + ORG 2766 showed a severe loss in their CAPs and CM, except for one showing intermediate loss. All animals from the group treated with cisplatin alone showed a severe loss in their CAPs and CM. Endolymphatic hydrops was present in all animals from the cisplatin- and the cisplatin + ORG 2766-treated groups. These data indicate that daily, concomitant administration of ORG 2766 may reduce OHC loss and subsequent degeneration of the organ of Corti in cisplatin-treated guinea pig cochleas.

UI MeSH Term Description Entries
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D002452 Cell Count The number of CELLS of a specific kind, usually measured per unit volume or area of sample. Cell Density,Cell Number,Cell Counts,Cell Densities,Cell Numbers,Count, Cell,Counts, Cell,Densities, Cell,Density, Cell,Number, Cell,Numbers, Cell
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
D003689 Vestibular Nucleus, Lateral Vestibular nucleus lying immediately superior to the inferior vestibular nucleus and composed of large multipolar nerve cells. Its upper end becomes continuous with the superior vestibular nucleus. Deiter Nucleus,Lateral Vestibular Nucleus,Deiter's Nucleus,Nucleus Vestibularis Lateralis,Nucleus Vestibularis Magnocellularis,Nucleus of Deiters,Deiters Nucleus,Nucleus Vestibularis Laterali,Nucleus Vestibularis Magnocellulari,Nucleus, Deiter,Nucleus, Deiter's,Nucleus, Lateral Vestibular,Vestibularis Laterali, Nucleus,Vestibularis Lateralis, Nucleus,Vestibularis Magnocellulari, Nucleus,Vestibularis Magnocellularis, Nucleus
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
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
D006056 Golgi Apparatus A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990) Golgi Complex,Apparatus, Golgi,Complex, Golgi
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

Related Publications

J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
June 2000, Hearing research,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
October 1993, Brain : a journal of neurology,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
May 1993, Annals of the New York Academy of Sciences,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
September 1990, European journal of pharmacology,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
September 1993, Hormones and behavior,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
October 1985, Acta psychiatrica Scandinavica,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
July 1979, Physiology & behavior,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
October 1985, Acta psychiatrica Scandinavica,
J C de Groot, and F P Hamers, and W H Gispen, and G F Smoorenburg
January 1985, Neuropsychobiology,
Copied contents to your clipboard!