The effect of nerve growth factor, ciliary neurotrophic factor, and ACTH analogs on cisplatin neurotoxicity in vitro.

Abstract:

:Cisplatin, used to treat ovarian, bladder, and testicular cancers, causes a sensory dose-limiting neuropathy. Preliminary observations in humans and animals suggest that nerve damage may be prevented by ACTH analogs, particularly those belonging to the melanocortin class, and by nerve growth factor (NGF). We established a rat embryo dorsal root ganglion model to study cisplatin neurotoxicity. The drug reproducibly inhibited axonal growth at concentrations similar to that known to produce toxicity in neurons. The inhibition was prevented in a dose-dependent fashion by simultaneous exposure to alpha-melanocyte stimulating hormone (alpha-MSH) or ACTH but not by excess NGF or ciliary neurotrophic factor (CNTF). The ACTH peptides were not effective in preventing suramin-induced neurotoxicity in the same model. Drug interaction and dose-response studies showed that ACTH and alpha-MSH do not act by potentiation of NGF action. ACTH analogs appear to protect against cisplatin-induced neurotoxicity directly at the cellular level.

journal_name

Neurology

journal_title

Neurology

authors

Windebank AJ,Smith AG,Russell JW

doi

10.1212/wnl.44.3_part_1.488

subject

Has Abstract

pub_date

1994-03-01 00:00:00

pages

488-94

issue

3 Pt 1

eissn

0028-3878

issn

1526-632X

journal_volume

44

pub_type

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