Journal of neuroscience research
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Sensory neuropathy is a serious side effect of anti-tumour drugs such as cisplatin and taxol. There are indications that an analogue of the adrenocorticotrophic hormone 4-9 fragment (ACTH4-9: Met(O2)-Glu-His-Phe-D-Lys-Phe) can prevent these neurotoxic effects. We studied the potential protective effects of this analogue in cultures of chick dorsal root ganglia and rat Schwann cells treated with cisplatin or taxol to gain insight into the mode of action and characteristics of this neuroprotection. ⋯ In addition, cisplatin was more toxic to Schwann cells than taxol; 3-10 micrograms/ml cisplatin significantly reduced their laminin content, total protein, 2',3'-cyclic nucleotide 3'-phosphodiesterase activity, and cell division. The ACTH4-9 analogue (0.01 nM-100 nM) had no effect on the migration of cells out of the DRGs and could not prevent the toxic effect on the Schwann cells. These data support our hypothesis that the neuroprotective effect of ACTH4-9 analogue is brought about by a direct action on neurons, possibly by replacing a Schwann-/satellite-cell derived trophic factor.