The effect of 1,25 dihydroxyvitamin D3 on HCl/Ethanol-induced gastric injury in rats.

This study evaluated ulceroprotective and antioxidant effect of 1,25 dihydroxyvitamin D3 against gastric damage in rats. Rats were treated intraperitoneally with either 1,25 dihydroxyvitamin D3 (0.25 µg/kg) or saline for 14 days. On day-15, the non-selective cyclooxygenase inhibitor indomethacin (10 mg/kg; subcutaneously), the inhibitor of sulfhydryl groups N-ethylmaleimide (10 mg/kg; intraperitoneally) or ATP-sensitive K+ channel blocker glibenclamide (10 mg/kg; orally) was given prior to 1,25 dihydroxyvitamin D3. Animals were euthanized at 60 min post ulcerogenic challenge (0.3 M HCl and 60% ethanol (0.2 mL; orally). Stomach and blood were collected for biochemical and histological evaluations. HCl/Ethanol group revealed severely damaged mucous and glandular epithelium with diffuse hemorrhage and inflammatory cell infiltration (microscopic score: 10.67 ±â€¯0.67 and ulcer index: 33.13 ±â€¯5.09). 1,25 dihydroxyvitamin D3 decreased the extent of damage (microscopic score: 6.80 ±â€¯0.02 and ulcer index: 19.00 ±â€¯4.34; p < 0.05), and the elevations in gastric malondialdehyde level (p < 0.001), myeloperoxidase activity (p < 0.001), nuclear factor-κB expression (p < 0.05), and apoptotic index (p < 0.05) following HCl/Ethanol challenge. Decreased gastric glutathione following HCl/Ethanol administration was restored by 1,25 dihydroxyvitamin D3 (p < 0.01). These findings demonstrated protection of the gastric mucosa against HCl/Ethanol-induced injury by 1,25 dihydroxyvitamin D3 via attenuation of inflammatory reaction, oxidative stress and apoptosis.

Treatment with milk thistle extract (Silybum marianum), ursodeoxycholic acid, or their combination attenuates cholestatic liver injury in rats: Role of the hepatic stem cells.

BACKGROUND/AIMS: Cholestasis, which results in hepatic cell death, fibrosis, cirrhosis, and eventually liver failure, is associated with oxidative stress. The aim of this study was to evaluate the effects of milk thistle (MT, Silybum marianum) and ursodeoxycholic acid (UDCA) or their combination on the activation of hepatic stem cells and on the severity of cholestasis liver injury in rats. MATERIALS AND METHODS: Under anesthesia, bile ducts of female Sprague Dawley rats were ligated (BDL) or had sham operation. BDL rats were administered saline, UDCA (15 mg/kg/d), MT (600 mg/kg/d), or UDCA+MT by gavage for 10 days. On the 11th day, rats were sacrificed and blood and liver samples were obtained. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic malondialdehyde (MDA) levels, and myeloperoxidase (MPO) activity were measured. Hepatic injury, a-smooth muscle actin expression, and stem cell markers c-kit, c-Myc, Oct3/4, and SSEA-1 were histologically determined. RESULTS: Histological scores, serum ALT, and hepatic MDA levels were higher in BDL group than in the sham rats, while all treatments significantly reduced these levels. The reduction in ALT was significantly greater in UCDA+MT-treated group than in other treatment groups. c-Kit, c-Myc, Oct3/4, and SSEA-1 were increased in saline-treated BDL group with respect to sham-operated control group, and these markers were significantly reduced in all treatment groups. CONCLUSION: In addition to a modulatory effect on the stem cell-induced regenerative response of the liver, UDCA, MT, and their combination demonstrated similar anti-inflammatory and antiproliferative effects on cholestasis-induced hepatic injury.

Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats.

Epidemiological and experimental studies have demonstrated that cigarette smoking intensifies gastric ulceration. Although nicotine can act as an anxiolytic and antidepressant, its withdrawal may also lead to increased anxiety and depression. In order to associate the toxic actions of nicotine on gastric mucosa with alterations of anxiety level and to evaluate the impact of nicotine withdrawal on the anxiety level and the severity of ulcer, an acetic acid-induced ulcer model was used. Male Sprague-Dawley rats were given either tap water or nicotine bitartarate (50µg/ml in drinking water) for 15 days, while another group of rats had 5 days of withdrawal following 10 days of nicotine treatment. Ulcer was induced by acetic acid on the 15th day of the treatments, and the rats were followed for 3 days until they were decapitated and the gastric tissues were obtained. Using the hole-board test, basal anxiety levels measured on the first day of the treatments were compared with the measurements made at the early and late phases of ulcer induction. Chronic administration of nicotine did not have a potentiating effect on acetic acid-induced gastric ulcer, since the gastric injury, as assessed by both macroscopic and microscopic evaluation and increased gastric myeloperoxidase activity indicating neutrophil recruitment, was not exaggerated or attenuated by nicotine intake. On the other hand, nicotine withdrawal attenuated gastric mucosal injury, despite an increased level of anxiety. Smoking cessation, which triggers the onset of depressive symptoms with nicotine withdrawal, still has a worthwhile positive effect on the gastric mucosa.