Effect of chemical ablation of myenteric neurones on intestinal cell proliferation.
The duodenum or descending colon of male Wistar rats (average weight 60 g) was treated by a serosal application of a 0.2% solution of benzalkonium chloride (BAC) for 30 min. Control animals were treated with 0.9% (physiological) saline. The rats were allocated to four groups: Group DC (N = 8) in which the duodenum was treated with physiological saline; Group DB (N = 8) in which the duodenum was treated with BAC; Group CC (N = 7) in which the descending colon was treated with physiological saline and Group CB (N = 7) in which the descending colon was treated with BAC. After treatment, the animals were followed up for 5 months. At the end of the experiment, the animals were injected intraperitoneally with vincristine sulphate before sacrifice. Three segments were removed from the duodenum and descending colon for neuronal counting, catecholamine and serotonin measurements and morphokinetic studies of the epithelium. The following results were obtained: (1) there was a significant reduction in neurone number in the myenteric plexus of segments treated with BAC; (2) in the denervated intestinal segments, catecholamine levels were unchanged whereas serotonin levels were increased; (3) epithelial hyperplasia was observed in the denervated duodenum and descending colon; and (4) crypt cell production rate in the duodenum was similar in groups DC and DB but was significantly increased in the descending colon in group CB as compared with controls (CC). The present findings indicate that selective myenteric neuronal denervation caused by benzalkonium chloride plays a causative role in the hyperplasia and crypt cell production rate of the intestinal epithelium (duodenum and descending colon). These changes are probably induced by functional imbalance by the surviving neuronal elements in the gut, implicating neurotransmitters such as acetylcholine, noradrenaline, serotonin, somatostatin and vasoactive intestinal peptide.
Zucoloto
S
S
Department of Pathology, University of São Paulo, Ribeirão Preto, Brazil.
Diaz
J A
JA
Oliveira
J S
JS
Muccilo
G
G
Sales Neto
V N
VN
Kajiwara
J K
JK
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology; D002395:Catecholamines / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000032:analysis / Q000166:cytology / Q000294:innervation; D003714:Denervation; D004386:Duodenum / Q000032:analysis / Q000166:cytology / Q000294:innervation; D004847:Epithelial Cells; D007422:Intestines / Q000032:analysis / Q000166:cytology* / Q000294:innervation; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis
D001548:Benzalkonium Compounds; D002395:Catecholamines; D012701:Serotonin