Biomedical subjects

H K Seitz

Publications and source records attributed to H K Seitz.

111 records · Page 7Linked to original sources

PubMedDate not supplied

The role of gastrointestinal factors in alcohol metabolism.

Although the liver is the major organ responsible for ethanol metabolism, such metabolism also occurs in the gastrointestinal (GI) tract. However, compared to the liver, GI metabolism of ethanol is quantitatively much lower. Various enzyme systems have been characterized in GI mucosal cells including various isozymes of alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP 2E1) and catalase. Gastric ADH activity is one factor by which first pass metabolism (FPM) is influenced and its activity is modulated by genetics, gender, age, drugs and gastric morphology. Another important factor in FPM of ethanol is the speed of gastric emptying. In addition to mucosal ethanol metabolism, ethanol can also be oxidized by many bacterial species in the upper GI tract including oropharynx and stomach as well as in the large intestine. GI metabolism of ethanol may influence systemic bioavailability of ethanol and may lead to local toxicity most likely mediated by acetaldehyde. Such toxicity could be of importance in ethanol-associated carcinogenesis.

Acetaldehyde↗

PubMedDate not supplied

Helicobacter pylori infection decreases gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol in man.

BACKGROUND/AIMS: Ethanol is metabolized by alcohol dehydrogenase in the human stomach. This metabolism contributes to the so-called first-pass metabolism of ethanol which is affected by gender, medication, and morphological alterations of the gastric mucosa. Recently, it has been shown that Helicobacter pylori is capable to oxidize ethanol to acetaldehyde in vitro. Since H. pylori also injures gastric mucosa, the present study examines the effect of this bacterium on gastric alcohol dehydrogenase activity and systemic availability of ethanol in vivo. METHODS: Thirteen volunteers (7 men and 6 women, aged 18-52 years) with gastric H. pylori infection diagnosed by a positive CLO test and positive gastric histology received ethanol (0.225 g/kg) either orally or intravenously before and after H. pylori elimination to determine systemic availability of ethanol. In addition, gastric biopsy specimens were taken from all subjects before and after H. pylori elimination for histological assessment of mucosal alterations and determinations of gastric alcohol dehydrogenase activity and phenotype of the enzyme. RESULTS: In the presence of H. pylori the first-pass metabolism of ethanol was found to be significantly reduced (625 +/- 234 vs. 1,155 +/- 114 mg/dl/min, p = 0.046). This reduction of first-pass metabolism of ethanol was associated with a significant decrease in alcohol dehydrogenase activity (4.8 +/- 1.5 vs. 12.1 +/- 2.3 nmol/mg protein x min, p < 0.05) and an increase in the severity of mucosal damage as determined by a histological score (p < 0.05). CONCLUSIONS: H. pylori infection leads to gastric mucosal injury which is associated with a decrease in gastric alcohol dehydrogenase activity and first-pass metabolism of ethanol. Ethanol metabolism by H. pylori does not play an important role in vivo. However, gastric morphology is one important factor determining systemic availability of ethanol in man.

Adolescent↗

PubMedDate not supplied

Antifibrotic properties of botanicals in chronic liver disease.

Cirrhosis of the liver is a major complication of various chronic liver diseases and results from excess production and decreased degradation of extracellular matrix. Proinflammatory cytokines, toxic metabolites and certain drugs can trigger enhanced fibrogenesis in hepatic stellate cells and myofibroblasts, the major matrix-producing cells. Since treatment of established cirrhosis is limited, therapeutic interventions that inhibit or mitigate fibrogenesis are needed. Numerous drugs have been investigated for their antifibrotic potential and botanicals constitute a significant fraction of them. Colchicine has been used to treat various chronic liver diseases with controversial results. To date, there is a lack of studies in appropriate animal models and well-controlled human trials to demonstrate its antifibrotic properties. Silymarin has so far failed to clearly show an antifibrotic effect in human studies, whereas animal experiments suggest that this mixture of flavolignanes may be beneficial in patients which have not yet developed cirrhosis. Animal studies indicate an antifibrotic potential of Shosaiko-to, a herbal combination frequently used in China and Japan for the treatment of chronic viral hepatitis, but mechanisms of action need to be further explored. Other botanicals include trans-resveratrol, a flavonoid extracted from grapevine, and Salvia miltiorrhiza which were shown to interfere with the process of hepatic stellate cell activation. Herbal combinations, such as compound 861 and LIV.52 were advocated as antifibrotics or hepatoprotectives, but studies in humans have either been of questionable design or resulted in cessation of the trial due to adverse outcomes.

Animals↗