Cysteamine-colon and cysteamine-duodenum lesions in rats. Attenuation by gastric pentadecapeptide BPC 157, cimetidine, ranitidine, atropine, omeprazole, sulphasalazine and methylprednisolone.
Recently, we showed cysteamine-duodenal lesions without gastric acid, since they were induced also in gastrectomized rats, as in naive rats, and they were inhibited by the novel stomach pentadecapeptide BPC 157 as well as standard antiulcer drugs (i.e. cimetidine, ranitidine, omeprazole, bromocriptine, atropine). Therefore, as an advantage of considering cysteamine as a directly acting cytotoxic agent and mentioned agents as direct cytoprotective agents, the present focus was on the ulcerogenic effect of cysteamine and protective effect of gastroduodenal antiulcer agents outside upper gastrointestinal tract (i.e. in colon). Intrarectal administration of the cysteamine (200 or 400 mg/kg b.w) produced severe colon lesions (i.e. transmural inflammation with serosal involvement) in rats (30 min-72 h-experimental period), apparently distinctive from smaller lesions after non-specific irritant enema [diluted HCl solution, pH 3.8 (adjusted to pH of cysteamine solution (pH 3.8)]. All of the tested antiulcer agents were applied simultaneously with cysteamine enema (8 cm from the anus, in a volume of the 1.0 ml/rat) intraperitoneally (i.p.), intragastrically (i.g.) or intrarectally (i.r.). Pentadecapeptide BPC 157 (10 microg or 10 ng/kg b.w.), given in either regimen, previously shown to have, besides others, a particular beneficial activity just in the intestinal mucosa, inhibited these cysteamine colon lesions (assessed after 30 min, 60 min, 180 min, 24 h, 48 h, 72 h following cysteamine in a dose of either 200 or 400 mg/kg i.r.). Cysteamine-colon lesions were also attenuated by standard antiulcer agents (mg/kg b.w.), given i.p., i.g., or i.r., such as ranitidine (10), cimetidine (50), omeprazole (10), atropine (10), together with methylprednisolone (1), and sulphasalazine (50, i.r.), assessed 30 min following application of 200 mg of cysteamine. Finally, standard cysteamine duodenal lesions (assessed 24 h after a subcutaneous application of 400 mg/kg of cysteamine) were also attenuated by these agents application (given in the same doses, i.p., 1 h before cysteamine), with only exception to sulphasalazine. Thus, the extended cysteamine specific ulcerogenic effect, cysteamine colon/duodenum lesion-link and an extenuation of agents protection from upper to lower part of gastrointestinal tract (i.e. stomach pentadecapeptide BPC 157, standard antiulcer agents, cimetidine, ranitidine, atropine, omeprazole) and vice versa (remedies for inflammatory bowel disease) evidenced in the present study may be potentially important for both further experimental and clinical research.
Sikiric
P
P
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, POB 916 Zagreb, Croatia. sikiric@mef.hr
Seiwerth
S
S
Grabarevic
Z
Z
Balen
I
I
Aralica
G
G
Gjurasin
M
M
Komericki
L
L
Perovic
D
D
Ziger
T
T
Anic
T
T
Prkacin
I
I
Separovic
J
J
Stancic-Rokotov
D
D
Lovric-Bencic
M
M
Mikus
D
D
Staresinic
M
M
Aralica
J
J
DiBiaggio
N
N
Simec
Z
Z
Turkovic
B
B
Rotkvic
I
I
Mise
S
S
Rucman
R
R
Petek
M
M
Sebecic
B
B
Ivasovic
Z
Z
Boban-Blagaic
A
A
Sjekavica
I
I
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003543:Cysteamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008775:Methylprednisolone / Q000494:pharmacology*; D009336:Necrosis; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012460:Sulfasalazine / Q000494:pharmacology*
D000897:Anti-Ulcer Agents; D005765:Gastrointestinal Agents; D005938:Glucocorticoids; D010446:Peptide Fragments; D011506:Proteins; D012460:Sulfasalazine; D003543:Cysteamine; C083833:BPC 157; D008775:Methylprednisolone