Characterization of mitomycin C-induced gastrointestinal damage. II. In vitro everted sac experiment.
The everted gut sac technique was employed to clarify the effects of preadministration of mitomycin C (MMC) on intestinal transport of various drugs. Loss of intestinal tissue weight and increase in mucosal-to-serosal fluxes of passively absorbed drugs were noted in the case of MMC pretreatment, although the extent of the latter effect varied according to the inherent absorbability of each drug. The maximal effect of MMC on intestinal tissue weight and transport of sulfanilamide, a model of a passively absorbed drug, was observed 48 hr after pretreatment. The increase in the transfer of sulfanilamide correlated well with the MMC-induced decrease in intestinal tissue weight. These phenomena may result from the shortened transfer distance from mucosal to serosal fluid and impaired barrier function of the intestinal mucosa. On the other hand, transport of actively absorbed 3-O-methyl-D-glucose was not influenced by MMC pretreatment, which could be explained by an increment in the passive permeation counterbalancing the decrement in the active permeation. The present study also suggested that the measurement of transport of drugs through everted gut sacs might be useful as a simple and qualitative index of gastrointestinal mucosal damage.
Hamaura
T
T
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Mizuno
M
M
Nakane
S
S
Hashida
M
M
Sezaki
H
H
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008757:Methylglucosides / Q000493:pharmacokinetics; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D008757:Methylglucosides; D008937:Mitomycins; D019325:3-O-Methylglucose; D016685:Mitomycin