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Previous research suggested that low doses of ethanol (ETOH) may have a protective effect against stress: We now report confirmation and extension of that preliminary study. Male Sprague-Dawley rats were injected with 0.50 g/kg ETOH (10% w/v) or an equivalent volume of saline and randomly assigned to one of four groups in Experiments I and II (saline-stress, saline-nonstress, ethanol-stress, ethanol-nonstress). In Experiment III, only two groups were tested (ethanol-stress, saline-stress). The stressors consisted of 30 trials (intertrial interval 60 s) of a 2-s duration 0.40 mA foot shock (Experiment I), 90 min restrain stress at 21 degrees C (Experiment II) or 10 min tail-pinch (Experiment III). In Experiments I and II, plasma nonesterified fatty acids (NEFA) were significantly increased in the saline-stress groups compared to the saline-nonstress or ethanol-nonstress groups. In contrast, subjects treated with ETOH and stress had significantly lower levels of plasma NEFA than saline-stress subjects in Experiments I and III. Plasma corticosterone was significantly elevated in response to stress. Subjects in the ethanol-stress groups had significantly lower levels of plasma corticosterone than subjects in the saline-stress group (Experiments I and II). These results suggest that ETOH has some protective effect against stress-induced increases in plasma corticosterone and NEFA. Furthermore, this finding may be generalized to several different types of stressors.

Rats were screened in an alcohol-water free-choice paradigm and divided into low-ethanol preferring (1.5–2.5 g/kg/day), medium-ethanol-preferring (2.5–4.5 g/kg/day) and high-ethanol-preferring (4.5–6.0 g/kg/day) groups. In addition, a non-ethanol-exposed group was included. Each of these groups was again subdivided with half the animals in a group being food deprived for 16 hr, and the other half having ad lib access to food. All rats were then subjected to restraint in the supine position in a cold (4–6°C) environment for 3 hr. Significant differences in ulcer incidence and severity (cumulative length of the ulcers expressed in millimeters) occurred, suggesting that higher intake of alcohol is associated with greater ulcer severity. This pattern occurred for both food-deprived and non-deprived animals.

Rats screened for voluntary ethanol intake (high, medium, and low ethanol-preferring rats and non-ethanol-exposed controls) were given acute immobilization stress either immediately following the ethanol screening procedure, or after a 20 day period without access to ethanol. Among animals examined for stress responses immediately after ethanol screening, it was observed that water-only control rats developed significantly less frequent and less severe gastric stress ulcers than rats in all ethanol-exposed groups. This result suggests that ethanol, stress and routine handling may have contributed to ulcer formation in these animals. In contrast, among rats tested for stress responses after 20 days without ethanol, it was observed that the high ethanol-preferring animals showed less severe stress ulcers. These results indicate that among high ethanol-consuming animals, the presence of ethanol enhances ulcer severity, while prior experience with ethanol consumption does not appear to predispose rats to exacerbated stress gastric pathology.

Several factors contribute to the development of gastric erosions, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and stress. These factors can cause or worsen gastrointestinal ulcers by activating inflammatory pathways or by altering gastric mucosal blood flow. Dapsone is an antimicrobial compound with anti-inflammatory properties. The aim of this study was to evaluate the protective effects of dapsone against gastric erosions induced by alcohol, stress, or indomethacin. Gastric damage was induced in male rats in three different experimental models: ethanol (5 ml/kg, p.o.)-, water-immersion stress-, and indomethacin (30 mg/kg, p.o.)- induced ulcer. Rats in each of these three experimental models were divided into five groups: Normal group, 2. Control group (gastric damage+vehicle), 3. Gastric damage+dapsone 1 mg/kg, 4. Gastric damage+dapsone 3 mg/kg, 5. Gastric damage+dapsone 10 mg/kg. In this study, the J- score ulcer index and histopathological assessment were performed. In addition, inflammatory cytokines levels, NF-κB expression, and MPO activity were determined. Dapsone reduced the tissue injuries and erosion area in all three experimental groups compared to the control group. In addition, serum levels of inflammatory cytokines, TNF-alpha, and IL-1β were reduced in the dapsone treatment groups. The expression of NF-κB and tissue concentration of myeloperoxidase (a marker of neutrophil activation) was also reduced in rats given dapsone. To conclude, dapsone exhibits significant protective effects against the development of experimental gastric erosions in rats, and these effects seem to be related to its anti-inflammatory and antioxidant properties.