Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was carried out to examine the effect of single or consecutive administration of T-2588 on liver of male rat injured by the administration of D-galactosamine X HCl. The T-2588 was orally given to hepatic-injured rats at doses of 125 mg/kg and 1,000 mg/kg singly or for consecutive 5 days. A 10 ml/kg dose of the vehicle was orally given to control rats. The results obtained were summarized below. Single administration of T-2588. Twenty-four hours after a single administration of T-2588, the liver taken from control rats apparently indicated galactosamine-induced hepatitis. No drug-related alterations were observed in hepatic functional test, liver weight and histological examinations at either dose of T-2588. Galactosamine-induced hepatitis was not affected by a single administration of T-2588. Consecutive administration of T-2588. Twenty-four hours after a 5-consecutive-day administration of T-2588, galactosamine-induced hepatitis in control rats was restored to the normal state. The cure of galactosamine-induced hepatitis was not affected by a 5-consecutive-day administration of T-2588. The hepatic aldehyde dehydrogenase activity in hepatic-injured rats was not affected by a 5-consecutive-day administration of T-2588.
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PMID:[Effect of single or consecutive administration of T-2588 on hepatic-injured male rats]. 379 80

The Long-Evans Cinnamon (LEC) rat is a mutant strain established from Long-Evans rats that displays spontaneous hepatitis and liver cancer. We previously demonstrated that LEC rats died of acute ethanol intoxication after being fed a liquid diet containing 5% ethanol. Furthermore, we found that both alcohol dehydrogenase (ADH) and aldehyde dehydrogenase activities were remarkably suppressed in the liver of LEC rat, compared with Wistar rats. In the present study, we further investigated ethanol metabolism in the non-ADH pathway and what caused the decrease of liver ADH activity in LEC rats. Blood ethanol concentration 5 hr after intraperitoneal administration of ethanol in LEC rats was higher than in the Wistar rats, indicating that ethanol oxidation was impaired in LEC rats. The expression of liver cytochrome P-450IIE1 in the LEC rat was as much as that in Wistar rats. Regarding decreased ADH activity in the liver of LEC rats, we examined an alternating purine-pyrimidine (CA) repeat-length polymorphism in the first intron of a class I ADH gene that would play a role in altering ADH activity. A polymerase chain reaction method was used to amplify the CA repeat in the first intron of this class I ADH gene, a nine CA repeat insertion and a point mutation were detected in LEC rats. These results suggest that this alternating sequence would modify transcription of the class I ADH gene in LEC rats. Thus, LEC rats have abnormal ethanol metabolism in the ADH pathway.
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PMID:Analysis of CA repeats in first intron of class I ADH gene in Long-Evans Cinnamon rats developing fatal intoxication after ethanol intake. 865 85

Long-Evans Cinnamon (LEC) and Long-Evans Agouti (LEA) rats are mutant strains established from Long-Evans rats. LEC rats display hereditary hepatitis and spontaneous hepatocellular carcinoma, but LEA rats do not develop liver diseases. We previously demonstrated that LEC rats had an impairment of liver aldehyde dehydrogenase (ALDH) activities, and all LEC rats which were fed with a liquid diet containing 5% ethanol died within 2 weeks. In the present study, we also found that LEA rats could not metabolize ethanol and died after being fed the same diet. Remarkably, in the liver of LEA rats, low Km ALDH activities were suppressed as much as in LEC rats. These results suggested that both LEC and LEA rats have hereditary deficiencies in ALDH. Nucleotide sequence analysis of ALDH2 genes in both LEC and LEA rats demonstrated that the point mutation of the codon for residue 67 encoding Gln to Asp was observed; this was not so in either Long-Evans rats or Wistar rats. This mutation in ALDH2 genes may cause inactivation of ALDR activity in LEC and LEA rats.
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PMID:Point mutation of aldehyde dehydrogenase-2 gene in mutant strains of Long-Evans rats. 906 17

Groups of patients suffering alcoholism and narcomania were examined for the effect of intoxication on the blood serum enzymes of mainly liver origin: alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as on thymol test. It has been shown that in patients with the first stage of alcoholism one could observe only functional disturbances in the liver: the increase of ADH activity which evidences for the induction of its synthesis. In patients with the first stage of opium narcomania one can record total hyperenzymenia, decrease of de-Rimis coefficient at the expense of more considerable increase of ALT activity than that of AST, as well as the sharp increase of thymol test--these are the signs of destructive and metabolic disturbances in the liver. In patients with the second stage of alcoholism one can observe the decrease of ALDH activity under the increase of ADH, AST, ALT activity and high thymol test-these are the signs of toxical hepatitis. Destructive and metabolic changes increase in the liver in the patients with the second stage of narcomania.
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PMID:[Comparative analysis of the effects of alcoholism and opium addiction on liver function]. 1139 20

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)]. Multiple logistic regression analyses revealed that heavy drinkers consuming >or=3 "go"s/day of sake (69 g of ethanol/day) showed an increased risk of HCC based on comparison of HCC cases with hospital controls [adjusted odds ratio (OR) = 13.5; 95% confidence interval (CI) 3.3-54.3] or CLD patients (adjusted OR = 7.0; 95% CI 2.5-19.2), whereas the overall risk was not elevated among light to moderate drinkers consuming <3 "go"s/day. Interestingly, light to moderate drinking was associated with an increased risk among those with ALDH2*1/*2 (adjusted OR = 4.5 or 2.0), but not among those with ALDH2*1/*1 (adjusted OR = 0.8 or 1.0; p interaction = 0.03 or 0.13). However, this gene-alcohol interaction was not observed for heavy drinking. Among light to moderate drinkers, people with the combination of ALDH2*1/*2 and ADH2*2/*2 revealed the highest risk of HCC. These findings indicate that the ALDH2 polymorphism may modify HCC risk among light to moderate drinkers.
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PMID:Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population. 1618 78

From the biomedical point of view alcohol is a Janus-faced dietary component with a dose-dependent effect varying from cardiovascular protection to cytotoxicity. Alcohol is absorbed in the upper gastrointestinal tract by passive diffusion, is quickly distributed throughout body water and is mostly eliminated through oxidation. The enzymatically-catalyzed oxidative degradation to acetaldehyde and further to acetate is primarily localized in the liver. In case of a low blood alcohol concentration (<0.5 per thousand) alcohol is predominantely metabolized by the enzyme aldehyde dehydrogenase; higher blood concentrations (>0.5 per thousand) are increasingly oxidized by the microsomal ethanoloxidizing system (MEOS). Alcohol consumption induces several metabolic reactions as well as acute effects on the central nervous system. Chronic alcohol consumption to some extent irreparably damages nearly every organ with the liver being particularly concerned. There are three stages of alcohol-induced liver disease (fatty liver, alcohol hepatitis, liver cirrhosis) and the liver damages mainly result from reaction products of alcohol degradation (acetaldehyde, NADH and reactive oxygen species). An especially dreaded clinical complication of the alcohol-induced liver disease is the hepatic encephalopathy. Its pathogenesis is a multifactorial and self-perpetuating process with the swelling of astrocytes being a crucial point. Swollen astrocytes induce several reactions such as oxidative/nitrosative stress, impaired signal transduction, protein modifications and a modified gene expression profile. The swelling of astrocytes and the change in neuronal activity are attributed to several neurotoxins, especially ammonia and aromatic amino acids. In alcohol addicted subjects multiple micronutrient deficiencies are common. The status of folic acid, thiamine, pyridoxine and zinc is especially critical.
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PMID:[Alcohol intake--a two-edged sword. Part 1: metabolism and pathogenic effects of alcohol]. 2297 May 27