Effect of bisacodyl and cascara on growth of aberrant crypt foci and malignant tumors in the rat colon.
Laxatives abuse has been associated with an increased risk for colon cancer. However, little is known about laxatives long-term carcinogenic potential in experimental studies. The present study was designed to investigate the effects of bisacodyl (4.3 and 43 mg/kg) and cascara (140 and 420 mg/kg) on azoxymethane (AOM)-induced aberrant crypt foci (ACF) and tumors. Animals, divided in 10 groups were treated with AOM and laxatives (alone or in combination) for 13 weeks. At the end of treatment animals were killed and the colon removed and analysed for the determination of ACF and tumors. Bisacodyl (4.3 and 43 mg/kg), given alone, did not induce the development of colonic ACF and tumors. Bisacodyl (4.3 mg/kg) coupled with AOM increased the number of crypt per focus, but not the number of tumors. Bisacodyl (43 mg/kg) significantly increased the number of crypt per focus and tumors. Cascara (140 and 420 mg/kg) did not induce the development of colonic ACF and tumors and did not modify the number of AOM-induced ACF and tumors. The results of the present study indicate a possible promoting effect of bisacodyl on rat colon carcinogenesis (especially at higher doses) and absence of any promoting or initiating activity of a laxative and diarrhoeal dose of cascara.
Borrelli
F
F
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Mereto
E
E
Capasso
F
F
Orsi
P
P
Sini
D
D
Izzo
A A
AA
Massa
B
B
Boggio
M
M
Mascolo
N
N
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D001726:Bisacodyl / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D031955:Rhamnus / Q000633:toxicity*
D002273:Carcinogens; D001726:Bisacodyl; D001397:Azoxymethane