Gastric lesions

Altanserin (100) is a representative of the thiaquinazolinones. This serotonin antagonist is said to prevent gastric lesions. One method for preparation of this compound involves first preparation of isothiocyanate derivative 99, by reacting 4-fluorobenzoylpiperidine with 2-bromoethylamine and then converting the intermediate to the isothiocyanate with thionyl chloride and base. Condensation of 99 with methyl anthranilate (98) probably proceeds initially to a thiourea. Cyclization by ester-amide interchange leads to altanserin (100) [28]. 

Fig. 8 Effects of bupleiiran 2IIb and 2IIc on HCl/ethanol induced gastric lesions in mice (Reproduced with permission from ref. 6. copyright 1994 Carbohydrate Polymer)...

Effect of GL-BIII on HCl/ethanol-induced gastric lesions in mice... 

Itoh, M. and Guth, P.H. (1985), Role of oxygen-derived ftee radicals in haemorrhagic shock-induced gastric lesions in the rat. Gastroenterology 88, 1162-1167. 

Itoh, Y., Takeyama, N, Kitazawa, Y. and Tanaka, T. (1992). Role of xanthine oxidase in endotoxin-induced gastric lesions. Gastroenterology 102, A89. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

The most potent activities (gastric antisecretory activity in the pylorus-ligated rat or anti-ulcer activity on stress-induced gastric lesion in rat) have been observed with compounds (30), (31) [106], (32) [107], (33) and (34) [108], which were shown neither to be histamine H2 receptor inhibitors nor to act as anticholinergic agents. Thus, the activity of compound (32), for example, has been reported to be superior to that of cimetidine [107],... 

Morini, G., Grandi, D., Bertaccini, G., 1995. (R)-alpha-methylhistamine inhibits ethanol-induced gastric lesions in the rat involvement of histamine H3 receptors Digestion 56, 145-152. 

A crude extract of Linderae umbellatae exhibited antipeptic and antiulcerogenic activity, and these effects were considered ascribable to the presence of tannins or related compounds. Nine condensed tannins (monomers, dimers, trimers, and tetramers) have been isolated and their antipeptic and antiulcer activity confirmed experimentally (pylorus ligated in rats and stress-induced gastric lesions in mice). 

Verschoyle RD, Little RA. 1981. The acute toxicity of some organolead and organotin compounds in the rat, with particular reference to a gastric lesion. J Appl Toxicol 1 247-255. 

Ratnasooriya, W.D., Premakumara, G.A.S. and Ananda, U.V.D.S. (1995) Protection by Murraya koenigii leaf extract against ethanol-induced gastric lesions in rats. Medical Science Research 23(1), 11-13. 

Non-Steroidal Anti-Inflammatory Agents (NASID), like indomethacin and acetyl-salicylic acid (aspirin), induce gastric lesions in man and in experimental animals by inhibition of gastric cyclooxygenase (COX) resulting in less formation of prostacyclin, the predominant prostanoid produced in the gastric mucosa. 

Instead of indomethacin, gastric lesions are induced by intravenous or oral doses of aspirin which can be prevented by exogenous PGE2 or PGI2 (Konturek et al. 1981). Furthermore, reserpine at a dose of 8 mg/kg i.p., or cysteamine hydrochloride at a dose of 400 mg/kg s.c. induce ulcers in rats (Tarutani et al. 1985). 

The number of animals with one or more lesions of the stomach is calculated as a percentage of the animals of the test group. Running various doses, an ED5q value can be calculated. Standard compounds which produce gastric lesions are Acetylsalicylic acid (10-100 mg/kg) naproxene (5-50 mg/kg) in-domethacin (1-10 mg/kg). 

Matsui et al. (2001) reported that the gastric mucosa in rats emits fluorescence of porphyrins at the onset of gastric lesions induced by diclofenac. HPLC analysis demonstrated that the fluorescent substances were mesoporphyrin and protoporphyrin. 

Pretreatment of rats v iihAronia melanocarpa fruit juice (5, 10, and 20mL/kg), which is rich in anthocyanins, decreased gastric lesions caused by indomethacin (Valcheva-Kuzmanova et ah, 2005). Indo-methacin-induced gastric mucosal damage in the rat was accompanied by the development of oxidative stress as evidenced by the accumulation of malondialdehyde. 

The Army s interim RfD of 1 x 10 " mg/kg per day for lewisite was based on two oral studies a two-generation reproductive study and a 90-day toxicity study in rats. In both studies, necrosis and hyperplasia of the forestomach were observed. After considering those studies and other potential studies, the subcommittee concludes that a 1987 teratogenicity study conducted in rabbits is more appropriate than the rat studies for deriving the RfD, because there is evidence that the rabbit might be more susceptible to lewisite than the rat. On the basis of the rabbit study, in which maternal mortality and gastric lesions were observed, the snbcommittee believes that the RfD for lewisite should be lowered from 1 x 10 mg/kg per day to 1 x 10 mg/kg per day. 

Hackett et al. (1987) and by ORNL), 46%, and 69%, respectively, were reported. In addition, gastric lesions (mucosal inflammation, edema, necrosis, and mucosal sloughing) were found at all doses, and teratogenic effects (fetal stunting and supernumerary ribs) were observed at the highest dose. On the basis of gastric lesions and mortality, the lowest-observed-adverse-effect level (LOAEL) for this study was 0.07 mg/kg per day. 

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