Cisplatin-induced gastrointestinal dysmotility is aggravated after chronic administration in the rat. Comparison with pica.
BACKGROUND
Chemotherapy induces nausea/emesis and gastrointestinal dysmotility. Pica, the ingestion of non-nutritive substances, is considered as an indirect marker of nausea/emesis in non-vomiting species, like the rat. Cisplatin is the most emetogenic antitumoral drug. In the rat, acute cisplatin induces pica and gastric dysmotility in a temporally related manner, but the effects of chronic cisplatin are not well known. This study analyzed the effects of chronic cisplatin on pica and on gastrointestinal motor function in the rat, using radiographic, non-invasive methods.


METHODS
Rats received saline or cisplatin (1-3 mg kg(-1), i.p.) once a week for four consecutive weeks. Serial X-rays were taken 0-8 h after administration of barium sulfate, which was given intragastrically immediately after the first and last cisplatin administrations and 1 week after treatment finalization. Pica (i.e., kaolin intake) was measured in isolated rats.


RESULTS
Cisplatin delayed gastric emptying and induced acute (during the 24 h following each administration) pica. Upon chronic administration, these effects were exacerbated. In addition, basal kaolin intake was enhanced (facilitated) and gastric distension induced. Delayed gastric emptying and gastric distension were not apparent 1 week after treatment, but basal kaolin intake was still elevated.


CONCLUSIONS
Whereas gastric dysmotility induced by cisplatin is parallel to the development of acute pica and might underlie facilitation of pica throughout chronic treatment, it does not explain its long-term maintenance. These findings should be taken into account in the search for new antiemetic strategies.
Departamento de Farmacología y Nutrición, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Madrid, Spain.
P A
PA
Cabezos
G
G
Vera
M I
MI
Martín-Fontelles
R
R
Fernández-Pujol
R
R
Abalo
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001831:Body Temperature / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D017615:Enteric Nervous System / Q000187:drug effects; D005247:Feeding Behavior; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D007616:Kaolin / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D010842:Pica / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D007616:Kaolin; D002945:Cisplatin