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Reactive oxygen species (ROS) have high chemical reactivity, due to the presence of an uncoupled electron in their molecules. Therefore, they cause tissue damages, especially by lipid peroxidation. Lipid peroxides are metabolized to malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). The increase of MDA and 4-HNE concentration indicates ROS-dependent tissue damage. Superoxide dismutase (SOD) is a main enzyme which neutralizes ROS into less noxious hydrogen peroxide. The decrease of SOD activity is related to impairment of protective mechanisms and leads to tissue injury. The hydrogen peroxide is further metabolized to water in the presence of reduced glutathione (GSH). The decrease of GSH level has detrimental consequences for cellular properties of antioxidative defence. Gastric mucosa, under stress conditions, exhibits intensification of lipid peroxidation (increase of MDA and 4-HNE), as well as the decrease of SOD activity and GSH concentration. This parameters appear to be useful for understanding of pathomechanisms of the origin of gastric mucosa damage in stress conditions. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) is a precancerous condition leading to the development of adenocarcinoma, associated with intestinal metaplasia. Nowadays, the rapid increase in the incidence of esophageal adenocarcinoma (EAC) has been observed worldwide. Despite the surgical treatment and the introduction of new chemotherapy forms, the 5-year period survival is still bad. In this paper, we provide an update on the pathogenesis of BE and EAC based on the interrelationship between prostaglandins (PG), growth factors (GF), GF receptors and peroxisome proliferator-activated receptors (PPARs) in chronic esophagitis, BE, and EAC. We also attempted to overview the involvement of cyclooxygenase (COX) products and pharmacological inhibitors of COX in the process of proliferation, angiogenesis and apoptosis resulting from their interactions with PPARs. Furthermore, the paper presents some experimental animal models of inducing an acute and chronic esophagitis and Barrett's esophagus, which are useful in understanding the pathogenesis of these diseases under clinical settings. Among the potential pathomechanisms, the cellular processes resulting from transactivation GF receptors by other factors such as PG and their biological activity in chronic inflammation and carcinogenesis are emphasized. Finally, we stressed the impact of the naturally occurring anti-oncogenic mechanisms and the recent advances in the innovative therapy against gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

In the present study on animal model of ulcerative colitis the influence of fungal colonization on the severity of inflammatory lesions in the colon and the course of their healing was evaluated. The results of our studies revealed, that significant fungal colonization (over 10(4) CFU/ml) delayed ulcer healing in the colon. It corresponded with the decrease of colonic blood flow (CBF) in the region of lesions and increase of interleukin (IL)-1beta, tumor necrosis factor(TNF)-alpha level in the serum. Introduction of antifungal therapy (fluconazole) or probiotic in rats inoculated with Candida accelerated the process of ulcer healing in the colon, expressed through the reduction of macro- and microscopic lesions in the colon and decrease of MPO, IL-beta TNF-alpha serum level.

Present-day methods of successful treatment of inflammatory bowel diseases (IBD) result from a better understanding of their pathophysiology due to advances in preclinical studies in this area of knowledge. Until recently microbiological studies have been focused on the bacterial aspects in pathogenesis of GI disorders, however in the last years an interest in the presence of fungi in the gastrointestinal tract has also increased. In this study using an animal model of ulcerative colitis, the impact of fungal colonization of the colon on the intensity of inflammatory changes in the colonic mucosa and the course of their healing was carried out. The macroscopic and microscopic criteria relating to the changes of weight of examined fragments of the colon were evaluated while assessing differences between groups tested. The intensity of intestinal inflammatory changes was determined by assessment of such parameters, as colonic blood flow (CBF), the level of MPO as a marker of colonic neutrophil infiltration intensity and the plasma levels of IL-1beta; and TNF-alpha concentrations. Results at the 3rd day after TNBS rectal administration revealed an increase of weight of isolated segments of inflammed colon, a decrease of CBF and the 4-5 fold increase of plasma MPO activity. Candida colonization of colon mucosa of rats delayed healing of colonic ulcers, induced by TNBS and this was associated with the increased expression of plasma IL-1beta and TNF-alpha levels. Administration of antifungal (fluconazole) or probiotic (Lacidofil) treatment to C. albicans infected rats exerted favorable effect on healing of inflammatory changes in the colon because the area of ulcerations in groups of rats treated with fluconazole or Lacidofil was significantly smaller in comparison with those inoculated with Candida solution only. Administration of fluconazole or Lacidofil significantly decreased the weight of colon segments, the MPO activity and the plasma IL-1beta and TNF-alpha levels, as compared with respective values in the group receiving Candida only. The results of our studies indicate the deteriorating influence of Candida on the healing process of inflamed colon in the animal model of ulcerative colitis. Concomitant therapy with probiotic or antifungal treatment improved healing of colonic lesions, decreased the weight of inflamed colonic tissue and also attenuated the MPO activity and plasma proinflammatory cytokines IL-1beta and TNF-alpha levels.