Enteric neuropathy evoked by repeated cisplatin in the rat
Article first published online: 7 FEB 2011
© 2011 Blackwell Publishing Ltd
Neurogastroenterology & Motility
Volume 23, Issue 4, pages 370–e163, April 2011
How to Cite
Vera, G., Castillo, M., Cabezos, P. A., Chiarlone, A., Martín, M. I., Gori, A., Pasquinelli, G., Barbara, G., Stanghellini, V., Corinaldesi, R., De Giorgio, R. and Abalo, R. (2011), Enteric neuropathy evoked by repeated cisplatin in the rat. Neurogastroenterology & Motility, 23: 370–e163. doi: 10.1111/j.1365-2982.2011.01674.x
- Issue published online: 11 MAR 2011
- Article first published online: 7 FEB 2011
- Received: 9 July 2010 Accepted for publication: 23 December 2010
- enteric neuropathy;
- gastrointestinal motility;
- nitrergic neurons
Background Acute administration of the antitumoral drug cisplatin can induce nausea/emesis and diarrhea. The long-term effects of cisplatin on gastrointestinal motility, particularly after repeated administration, are not well known. Because cisplatin is highly neurotoxic, myenteric neurons can be affected. Our aim was to study the prolonged effects of repeated cisplatin administration in a rat model, focusing on gastrointestinal motor function and myenteric neurons.
Methods Rats received saline or cisplatin (1 or 3 mg kg−1, i.p.) once weekly for 5 weeks. One week after treatment, both upper gastrointestinal transit and colonic activity were evaluated, and tissue samples from ileum, colon and rectum were processed for histological analysis. Intestinal transit was measured invasively (charcoal method). Colonic activity was determined electromyographically. The gut wall structure was evaluated in sections using conventional histology and immunohistochemistry. Whole-mount preparations from the distal colon were labeled for different markers, including nitric oxide synthase (NOS) and calcitonin-gene related peptide (CGRP) to determine relative proportions of myenteric neurons vs the total neuronal population labeled with HuC/D.
Key Results One week after repeated cisplatin exposure, the upper gastrointestinal transit rate and colonic activity were dose-dependently reduced. The number of NSE- or HuC/D-immunoreactive myenteric neurons per ganglion was decreased; the proportion of CGRP-immunoreactive neurons was decreased, whereas that of NOS-immunoreactive cells was increased.
Conclusions & Inferences Chronic cisplatin may induce an enteric neuropathy characterized by changes in myenteric neurons associated with marked gastrointestinal motor dysfunction.