Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution.
OBJECTIVE
To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis.


METHODS
Wistar rats received 5-FU (150 mg kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro.


RESULTS
On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day.


CONCLUSIONS
5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.
Soares
Pedro M G
PM
Centro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará, Rodolfo Teófilo, Fortaleza, Brazil.
Mota
José Maurício S C
JM
Gomes
Antoniella S
AS
Oliveira
Ricardo B
RB
Assreuy
Ana Maria S
AM
Brito
Gerly Anne C
GA
Santos
Armênio A
AA
Ribeiro
Ronaldo A
RA
Souza
Marcellus H L P
MH
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D005472:Fluorouracil / Q000633:toxicity*; D005746:Gastric Emptying / Q000187:drug effects; D005748:Gastric Fundus / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis; D007410:Intestinal Diseases / Q000139:chemically induced / Q000503:physiopathology*; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D008940:Mitotic Index; D052016:Mucositis / Q000139:chemically induced / Q000503:physiopathology*; D009195:Peroxidase / Q000032:analysis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D002217:Carbachol; D009195:Peroxidase; D005978:Glutathione; D005472:Fluorouracil