Duodenal ulcerogens

Szabo S, Silver EH, Gallagher GT, et al. 1983. Potentiation of duodenal ulcerogenic action of acrylonitrile by PCB or phenobarbital in the rat. Toxicol Appl Pharmacol 71 451-454. 

Recent data in our laboratories indicated the possible involvement of central and peripheral dopamine binding sites in the pathogenesis of duodenal ulceration. Structure activity studies with duodenal ulcerogens implicated dopamine as a putative mediator and/or modulator in duodenal ulceration. Using the cysteamine- or propionitrile-induced duodenal ulcer model in rats, we found that dopamine agonists (e.g., bromocriptine, lergotrile,... 

Figure 2. Duodenal ulcerogenic and adrenocorticolytic activities of terminal nitriles, amino and thiol alkanes. (Reproduced with permission from Ref. 34. Copyright 1980, International Institute of Stress.)...

The duodenal ulcerogenic action of propionitrile and cysteamine was confirmed and extended by several authors (J, 8, 25-32). The model, especially the rapidly developing cysteamine-induced duodenal ulcer, was actually introduced in several laboratories to routinely test drugs for anti-ulcer activity (7.8,27.33). The cysteamine model, a simple, fast, and inexpensive procedure, became especially useful after a chronic form of duodenal ulcer was developed ( ) and similarities between the model and human duodenal ulceration were noted (7-10). 

The groups consisted of 3-4 Sprague-Dawley female rats (160-180g). Each experiment was repeated at least twice and the results of those groups were pooled. The dopamine agonists MDO-NPA and NPA were injected sc once daily for seven days prior to the administration of cysteamine HC1 (Aldrich) 28 mg/100 g po three times with 3 h intervals. The dopamine antagonists NCA and (+)butaclamol were injected sc three times, 30 min before each dose of cysteamine. The animals were killed 48 h after the duodenal ulcerogen. The intensity of duodenal ulcer was evaluated on a scale of 0-3, where 0 = no ulcer, 1 = superficial mucosal erosion, 2 = transmural necrosis, deep ulcer, 3 = perforated or penetrated duodenal ulcer. 

Szabo, S. and Cho, C.H. (1988a) From cysteamine to MPTP stmcture-activity studies with duodenal ulcerogens. Toxicol. Pathol. 16, 205-212. 

Acrylonitrile alone has little tendency to produce duodenal ulcers in animals, but pretreatment with phenobarbital or Aroclor results in a marked increase in the incidence of such ulcers (Szabo et al. 1983, 1984). Although the mechanism of the ulcerogenic effect is not obvious, these data indicate that agents which enhanced mixed-function oxidase activity may also increase the toxicity of acrylonitrile. 

Documented effects Fruits are a rich source of polyvitamins. Oil from the fruits is used as an analgesic and to treat bums, frostbite, eczema, persistent wounds, as well as stomach and duodenal ulcers. The oil is used during radiation treatment for esophageal cancer (Tolmachev 1976). A study of the radioprotective action of a preparation of this species resulted in an 82 % survival rate in mice that received the treatment compared to no survival in irradiated control (Goel et al. 2002). Alcoholic extracts of leaves and fruits of sea buckthorn were found to inhibit chromium-induced free radical production, apoptosis, and DNA fragmentation, and restored the anti-oxidant stams to that of control cells. These extracts also were able to arrest the chromium-induced inhibition of lymphocyte proliferation (Geetha et al. 2002). Flavonoids isolated from the plant are reported to have antioxidant, anti-ulcerogenic, and hepato-protective properties (Yue et al. 2004). 

Myers CP, Hogan D, Yao B, et al. Inhibition of rabbit duodenal bicarbonate secretion by ulcerogenic agents histamine-dependent and -independent effects. Gastroenterology 1998 114 527-535. 

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