Enhancement of cell proliferation and prostaglandin biosynthesis by 1,8-dihydroxyanthraquinone in the rat large intestine.
The effects of 1,8-dihydroxyanthraquinone (DHAQ), a stimulant laxative named danthron, on cell kinetics and prostaglandin (PG) biosynthesis in the gastrointestinal tract were investigated in male 8-week-old F344 rats divided into three groups, each consisting of 10 animals. The animals in groups one, two and three were respectively given diets supplemented with 0%, 0.1% and 0.2% DHAQ for 24 days. PGE2 levels in the colorectal mucosa were significantly (P < 0.05 and 0.001) elevated after DHAQ treatment and showed some evidence of a dependence of DHAQ dose, consistent with the plasma PGE2 levels. BrdU-labeling indices in the large intestinal epithelium were also significantly (P < 0.01) increased, although the other portions of the gut such as the stomach and small intestine were not significantly affected. Excretion of the main urinary metabolite of PGE (PGE-MUM) was significantly (P < 0.001 or 0.01) increased whereas the urinary PGE2 concentration and total PGE2 excretion were not changed. Thus the results of the present study clearly indicate enhancement of cell proliferation by DHAQ in the large intestine epithelia, correlated with increased PGE2 levels in the large intestinal mucosa as well as the plasma, and possible support for the conclusion that quantitative analysis of urinary PGE-MUM, but not PGE2 itself, offer a useful approach for biomonitoring exposure to such stimulant laxatives.
Nishikawa
A
A
Biological Safety Research Center, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Kase
Y
Y
Hayakawa
T
T
Yanagisawa
T
T
Kanno
J
J
Hayashi
Y
Y
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002400:Cathartics / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000096:biosynthesis* / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007420:Intestine, Large / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011466:Prostanoic Acids / Q000378:metabolism / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344
D000880:Anthraquinones; D002400:Cathartics; D011466:Prostanoic Acids; C037830:11 alpha-hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid; D015232:Dinoprostone; C004315:danthron