Correlations of DNA, RNA and protein levels in duodenal mucosa with antiinflammatory potency and disposition to gut damage of non-steroidal agents. Comparative behaviour of glucametacine, indometacin, phenylbutazone and ibuprofen.
As far as molar ratio is concerned, glucametacine was half as potent as indometacin, twice as active as phenylbutazone and four times more effective than ibuprofen in preventing cotton granuloma. Both indometacin and phenylbutazone induced dose related gastrointestinal ulcerations and increase of 51Cr tagged erythrocytes in feces. The former drug displayed gut toxicity at anti-inflammatory doses, the latter at doses approximately four times larger. Glucametacine was still devoid of damaging effects at a dose ten times larger than the minimal one capable of inhibiting granuloma growth. Ibuprofen, too, failed to induce ulcers at all doses examined; however, it displayed a trend toward gut bleeding when doses that increased blood corticosterone were attained. Studies on duodenal mucosa showed that in rats on cotton granuloma, DNA, proteins and DNA:RNA ratio increase as compared to unimplanted rats. Glucametacine and phenylbutazone reversed the increase of DNA and proteins, respectively. Indometacin decreased all forementioned constituents of duodenal mucosa while inducing haemorrhages and ulcers on gut. Furthermore, in naive rats, unlike glucametacine and phenylbutazone, indometacin induced a decrease in protein content of duodenal mucosa. Differences in disposition of gut toxicity among glucametacine and other anti-inflammatory drugs are discussed.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004381:Duodenal Ulcer / Q000139:chemically induced; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000031:analogs & derivatives / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D012313:RNA / Q000378:metabolism*; D051381:Rats
D000893:Anti-Inflammatory Agents; D011506:Proteins; D012313:RNA; D004247:DNA; D010653:Phenylbutazone; D005944:Glucosamine; D007052:Ibuprofen; D007213:Indomethacin