bjectives : It is known that the NSAID can cause the ulcerative lesion on the small intestine but the precise pathophysiology was not established yet. This study was done to observe whether the NSAID has toxic effect on the small intestinal cell
and if
it has cytotoxicity, to investigate its mechanism.
Method : To observe the toxic effect of five NSAIDs (indomethacin, sulindac, aspirin,
ketoprofen, ibuprofen) upon the IEC18 cells originated from the ileum of the rat, the MTT
method was used, and to investigate its mechanism, ATP ratio (ATP in each NSAID divided
by ATP of control) was meseared.
Results :
1) Among the five NSAIDs, the cytotoxicity of indomethacin was most conspicuous that
the IEC18 cell survival rate was 0% in 300 ug/ml of indomethacin. The survival rate for
sulindac and ketoprofen decreased in proportion to the concentration up to 600 ug/ml where
the survival rate was 5.7% and 15.8%, respectively. For ibuprofen, there was no change in
cell survival rate up to 200 ug/ml, while in 400 ug/ml the survival rate was reduced to 4.1%.
For aspirin, the survival rate was strikingly high (53.5%) even in 1000 ug/ml.
2) The addition of PGE2 to the NSAIDs resulted in no significant changes in the cell
survival rate.
3) The addition of prednisolone to NSAIDs resulted in the increase of the survival rate by
less than 6.2% for indomethacin, sulindac, and aspirin. On the other hand, the addition of the
prednisolone of 2.5 ug/ml increased the survival rate by 16.2% and 21% respectively for
ketoprofen of 400 ug/ml and ibuprofen of 300 ug/ml.
4) The ATP ratios measured 3 days after application of NSAID to IEC18 cells were found
to be 52%, 37%, 34% and 42%, respectively for indomethacin of 200 ug/ml, sulindac of 300
ug/ml, ketoprofen of 500 ug/ml and ibuprofen of 300 ug/ml, all of which showed the strong
toxicity. On the other hand, the ATP ratio was found to increase up to 163% after application
of aspirin of 600 ug/ml, which showed the relatively weak toxicity.
Conclusion : From these results, each of the 5 NSAIDs shows a different level of toxicity
from one another, and the impaiment of oxygen metabolism, which can be seen from the
reduced ATP ratios, may be suggested as an important mechanism of cytoxicity.
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