Effects of smoking and Helicobacter pylori on prostaglandin concentrations in gastric and duodenal mucosa of patients with duodenal ulcer and duodenitis.

The aim of this study was to determine the level of endogenous prostaglandin E2 (PGE2), prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) in the gastric and duodenal mucosa of patients with duodenal ulcer and duodenitis. Besides, the investigation aimed at determining the effect of smoking and infection by Helicobater pylori on prostaglandin synthesis. The investigation comprised 62 patients with duodenal ulcer, 46 patients with duodenitis and 44 controls. The results of our investigation indicate that the decreased prostaglandin synthesis in gastric and duodenal mucosa determined in patients with duodenal ulcer may have a considerable role in development of duodenal ulcer. Furthermore, the harmful effects of smoking on the gastric and duodenal mucosa may be mediated by the decreased prostaglandin synthesis in the gastric and duodenal mucosa. However, Helicobacter pylori seems to affect the development of duodenal ulcer through other mechanisms.

Ketoconazole inhibits acetaminophen-induced hepatotoxicity in mice.

OBJECTIVE: To investigate the effect of ketoconazole on acetaminophen (AAP)-induced hepatotoxicity in mice. MATERIALS AND METHODS: Mice were given AAP intragastrically (300 mg/kg) and treated with ketoconazole (100 mg/kg intraperitoneally) or saline either 30 min before or 2-3 h after AAP administration. Mortality was recorded for 48 h, during which all mice given saline either died or recovered fully. Serum alanine and aspartate transaminase levels were determined 24 h after administration of AAP. Prostaglandin E2, thromboxane A2 and leukotriene C4 production was determined 6 h after AAP administration in the supernatants from the short-term culture of liver fragments by radioimmunoassay. RESULTS: Ketoconazole significantly decreased mortality and transaminase levels when given to mice either 30 min before or 2 h after AAP. Liver fragments from mice with AAP hepatitis produced greater quantities of prostaglandin E2, thromboxane A2 and leukotriene C4 than fragments from normal liver. Pretreatment of mice with ketoconazole or its addition to liver fragments ex vivo further increased the production of prostaglandin E2 and reduced the production of thromboxane A2. The effect of ketoconazole on leukotriene C4 synthesis was different in vivo (synthesis stimulation) from in vitro (synthesis inhibition). CONCLUSION: The protective effect of ketoconazole in AAP hepatitis is most probably mediated by modulation of eicosanoid synthesis by liver cells.

The effect of interleukin 1 alpha on acetaminophen-induced hepatotoxicity.

The protective effect of interleukin 1 alpha (IL-1 alpha) in mice with acetaminophen (AAP)-induced hepatitis was investigated. IL-1 alpha had a significant protective effect if given 2 or more hours (up to 24 hours) before AAP; it significantly reduced mortality of mice and decreased serum transaminase level. The maximal effect was obtained with the dose of 1000 U (166 ng/kg) IL-1 alpha. Pretreatment with IL-1 significantly increased the synthesis of prostaglandin E2 (PGE2) in samples of liver tissue from AAP-treated mice, but had no effect on the synthesis of leukotriene C4 (LTC4). Pretreatment with indomethacin (IMC) did not abrogate significantly the protective effect of IL-1. Thus, the hepatoprotective effect of IL-1 alpha can not be entirely explained by the stimulation of prostaglandin (PG) synthesis.