engleski

A now insight into cytoprotection, the role of pentadecapeptide ABP 157 and other anti-ulcer drugs.

Since definition of cytoprotection as an important phenomenon independent from gastric acid by A. Robert in Gastroenterology 1979, a direct evidence about the definitive role of gastric acid is not provided. In the first experiments (Sikiric et al., Dig.Dis.Sci, 1997) along with a widely proclaimed independency between Robert's cytoprotection and gastric acid secretion, a total gastrectomy was performed to further define this pentadecapeptide cytoprotective capacity, as a "direct" cytoprotective effect. Both theoretically and practically, gastrectomy could be taken as a new experimental improvement to create an acid-free environmental logically needed for cytoprotective studies. In this, a clear evidence about suggested non-acid (cytoprotective) phenomenology was based on at least two convincing experimental demonstrations. Firstly, like in the intact rats, cysteamine-duodenal lesions could be induced also in gastrectomized rats, with esophagoduodenal terminoterminal anastomosis (as emphasised, cysteamine in otherwise used commonly as a duodenal ulcerogen duo to its supposed effect on gastric acid hypersecretion). Secondly, the pentadecapeptide BPC 157 would antagonize the duodenal cysteamine lesions also in gastrectomized animals, an effect shared with standar antiulcer drugs (cimetidine, ranitidine, omeprazole, bromcriptine, atropine). Thus, a "direct cytoprotection" was evidenced for pentadecapeptide BPC 157 and standard antiulcer agents in totally gastrectomized rats' duodenum challanged with cysteamin (shown to have a damaging effect essentially independent from gastric acid). In the second experiments (Sikiric et al., Gastroenterology 1997), considering gastrectomized acid free rats as an ideal model for long-term cytoprotective studies, and expending these findings, pentadecapeptide BPC 157 qwas shown to markedly attenuate terminolateral esophagojejunal anastomosis-reflux esophagitis also over a quite prolonged period (1, 2, 4 weeks), having an effect (medication, per kg b.w., given in drinking water since 24 hours after surgery till sacrifice) superior then other reference agents. Relative to the control values, less damaged mucosa was noted in the rats drinking (12, 5 ml/rat daily) ranitidine (125 mg), sucralfate (725 mg) (dose per kg b.w.) after one week esophagitis, but not further oserved in later invervals (microscopical assessment). Compared with these results, pentadecapeptide BPC 157 (125 ug or 125 ng) attenuation of esophagitis were apparently more pronounced, and clearly appeared in all tested intervals, assessed either macroscopically or microscopically. Thus, despite limitation, a generalization supporting a direct importance of a common cytoprotective approach, and particularly the importance of the pentadecapeptide BPC, could be clearly provided. A useful, long-lasting cytoprotective activity (apparently more prominent in BPC 157-rats, than in referece agents) could be likely exemplified as a suitable therapy in various, otherwise resistant conditions, such as reflux esophagitis as well.

cytoprotection; BPC-157; antiulcer drugs

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