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.

Effects of cimetidine on broiler fattening and on stress-induced gizzard erosion in chicken.

The work describes the effects of cimetidine on stress-induced gizzard erosions (Experiment A) and the influence of the long-term application (42 days) of the same drug on weight gain and feed consumption during broiler fattening (Experiment B). For Experiment A, 60 male, three-day-old chicks were divided into two groups: C (n = 30)--control chicks treated with 0.5 ml saline; CIM (n = 30)--chicks treated with cimetidine in a dose of 5 mg/kg body weight (b. w.) intragastrically. All chicks were stressed using a modified water-immersion stress method according to which the chicks, after 24 h of feed deprivation, were immersed in tap water (17 degrees C) for a few seconds. Under chloroform anaesthesia ten chicks from each group were killed 1, 2 and 3 h after the stressing. The morphometric analysis of gizzard erosion (GE) and histopathological examinations of gizzards were performed for each chick. In Experiment B, 32 one-day-old broilers of both sexes were used. The control group was untreated (n = 16) while the CIM group (n = 16) was fed the same diet supplemented with 10 mg of cimetidine per kilogram of feed throughout the fattening period (42 days). The results of Experiment A showed decreased mean length of the GE in the cimetidine-treated birds as compared with the GE lesions of the controls. In Experiment B, the treated chicks had reduced liveweight (1835.1 g), carcass weight (1474.6 g) and increased feed consumption (2115 g of feed per kilogram of weight gain) compared to the controls in which the same parameters were 1898.5 g, 1574.2 g and 1797 g, respectively. The results show that while stress-induced GE of chicks can be medicated pharmacologically, long-term application of the same substance impairs the results of fattening.

Gizzerosine-induced histopathological lesions in broiler chicks.

1. The aim of this study was to investigate pathomorphological changes in broiler chicks fed with different doses of gizzerosine, a substance produced during the heat treatments of fish meal. 2. The experiment was carried out in Ross broiler chicks which were divided into three groups: group A received 100% of non-medicated commercial mash for broiler chicks. During an experimental 5-d period, 50% of commercial mash was replaced with unheated fish meal (0.65 ppm gizzerosine) in group B and in group C with heated fish meal (1.15 ppm gizzerosine). Fourteen chicks from each group were killed every day. Samples of gastrointestinal and lymphoid organs, lung, pancreas, liver, brain and kidney tissue were sampled for histopathological analysis. Organs were embedded in paraffin and stained with hematoxylin-eosin stain and using periodic acid-Schiff reagent (PAS) and Sudan III (frozen sections). 3. Necropsy did not reveal notable differences between treated groups. There were no significant histopathological changes in immunocompetent organs nor in the lungs, the pancreas, the kidney or the brain. Sharply demarcated multiple vacuoles were observed in the myocardium in group C toward the end of the experiment. In group C, the prevalent changes in the gizzard and the proventriculus were slight to severe cuticle erosions and oedema of the lamina propria with or without multiple vacuoles, respectively, towards the end of the experiment. The most prominent changes toward the end of the experiment were dispersed cell vacuolisation in duodenal, jejunual, ileal and caecal lamina propria in group C. 4. In conclusion, it should be emphasised that extra-gizzard gizzerosine-induced lesions are probably not mediated by H2-receptor stimulation, but could be a consequence of cellular hypoxia.