leukotriene-c4 and Stomach-Ulcer

Fibroblasts (FIB) play an important role in the wound-healing process. It is not known whether human skin and gastric FIB show different responses to regulatory compounds. In this study, we have examined the collagen production by these FIB after different stimuli. In vitro release of collagen into the medium by steady-state confluent human FIB cultures was assessed over a 24-hour period by 3H-proline incorporation into collageneous protein. Serum and epidermal growth factor increased collagen secretion in both types of FIB, but gastric FIB produced less collagen than skin FIB. Prostaglandin E1 inhibited collagen production in both types of FIB, but nonsteroidal anti-inflammatory drugs and interleukin-1beta, a cytokine involved in the wound-healing process, had opposite effects on gastric and skin FIB. The effects of lipoxygenase metabolites on collagen secretion was small, but different in both types of FIB. We conclude that, when compared to skin FIB, human gastric FIB produce less collagen and show pronounced different responses to different agents, which might be relevant to explain (in part) their clinical effects on ulcer healing. These data provide new insights into the wound-healing process.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Collagen; Epidermal Growth Factor; Fibroblasts; Humans; Interleukin-1; Leukotriene C4; Prostaglandins; Stomach Ulcer; Wound Healing

Cigarette smoking has been associated with peptic ulceration. However, the ulcerogenic mechanisms are still undefined. The aim of this study was to investigate the effects and possible mechanisms of cigarette smoke on ethanol- or cold-restraint stress-induced gastric damage.. Rats were exposed to cigarette smoke followed by either an ethanol (70%) challenge or cold-restraint stress. The severity of mucosal damage, levels of prostaglandin E2 and leukotriene C4, determined by radioimmunoassay, and neutrophil infiltration in the stomach were assessed.. Smoke dose-dependently potentiated ethanol-but not stress-induced ulcer. It reduced mucosal prostaglandin E2 and increased myeloperoxidase activity. Filtered cigarette smoke did not have these effects. The acidic fraction from the filters produced similar potentiating effects and also delayed ulcer healing. Mucosal leukotriene C4 and serum nicotine levels did not correlate with the mucosal injury in the stomach. Neutropenia abolished the ulcerogenic action and the increase of myeloperoxidase activity produced by both cigarette smoke and acidic fraction.. Reduction of prostaglandin E2 and increase in neutrophil accumulation in the gastric mucosa are responsible for the potentiating action of acute smoke exposure on ethanol-induced gastric damage. Substances other than nicotine could contribute to these adverse reactions in the stomach.

Topics: Acetic Acid; Animals; Cold Temperature; Dinoprostone; Ethanol; Gastric Mucosa; Leukotriene C4; Male; Nicotine; Peroxidase; Rats; Rats, Sprague-Dawley; Restraint, Physical; Smoking; Stomach Ulcer; Stress, Psychological; Tobacco Smoke Pollution

Systemic administration of capsaicin aggravates ethanol-induced injury of rat gastric mucosa. We evaluated the effect of subcutaneous administration of capsaicin on the gastric mucosa and on inflammatory mediators in saline- and ethanol-treated rats. Functional ablation of primary afferent C-fibers by capsaicin (total 100 mg/kg subcutaneous) tripled ethanol-induced damage. Pretreatment with ketotifen, a mast cell stabilizer (1 mg/kg) protected rat gastric mucosa from the amplified injury induced by capsaicin and ethanol. Tempol, a selective nontoxic cell-permeable nitroxide, completely prevented the amplified gastric ulceration induced by capsaicin and ethanol. This was accompanied by a significant decrease in leukotriene B4 and C4 generation. It is therefore suggested that mast cells and free radicals contribute to the amplified injury observed in rats pretreated with capsaicin and ethanol and that the pharmacological modulation of mast cell release and scavenging of free radicals may be of therapeutic efficacy in the prevention of gastric injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capsaicin; Cyclic N-Oxides; Ethanol; Free Radical Scavengers; Free Radicals; Gastric Mucosa; Ketotifen; Leukotriene B4; Leukotriene C4; Male; Mast Cells; Nerve Fibers; Platelet Activating Factor; Premedication; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; Spin Labels; Stomach Ulcer

Studies in pigs and rats were undertaken to explore further the role of leukotrienes following administration of NSAIDs on the development of gastrointestinal damage. Increased leukotriene C4 production occurred in the gastric circulation in the early stages after administration of a single dose of indomethacin (10 mg/kg i.g.) to pigs. Gastric and intestinal mucosal lesions by NSAIDs were prevented by both prior (2-5 h)+ 0.25 or 0h oral dosing of the 5-lipoxygenase inhibitor, MK-886, but not when only one of these doses was given. These results show the importance of enhanced peptidoleukotriene production in relation to microvascular damage from cyclooxygenase inhibition by NSAIDs.

Topics: Administration, Oral; Animals; Arthritis; Aspirin; Female; Gastric Mucosa; Indoles; Indomethacin; Injections, Subcutaneous; Intestinal Mucosa; Leukotriene Antagonists; Leukotriene C4; Lipoxygenase Inhibitors; Rats; Rats, Inbred Lew; Stomach; Stomach Ulcer; Swine