Content of Hepatic Reduced Glutathione in Chronic Alcoholic Patients: Influence of the Length of Abstinence and Liver Necrosis (original) (raw)
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Decreased production of glutathione in patients with cirrhosis
European Journal of Clinical Investigation, 1987
Studies in animals have demonstrated the central role of the liver in regulating the circulating pool of glutathione (GSH). Most of the hepatic GSH production is released into blood and most of the circulating GSH originates in the liver. We have estimated the production of GSH in eight healthy volunteers and eight patients with cirrhosis by an analysis of the kinetics of plasma GSH. The basal plasma concentrations of free GSH were 9.3 2.4 pM in healthy volunteers and 3.6f 1.1 ,UM in cirrhotics (P<O.OOl), and the concentrations of total GSH 16.6 f 6.2 PM in control subjects and 7.1 f 2.6 C(M in cirrhotics (P< 0.002). The concentration of GSH in the circulating pool depends on the input of GSH into this compartment and is inversely proportional to the volume of distribution of GSH (Vd) and to the fractional rate of elimination of GSH from plasma (ke1). Assuming that the kinetics of endogenously produced and exogenously administered GSH are identical, Vd and k,l can be calculated from the plasma concentration-time curve of a single i.v. injection of GSH. Both Vd (0.100f0.044 1 kg-' in controls and 0-1 3 1 k 0.043 1 kg-' in cirrhotics) and k,, (0.2718f0.0555 min-' in controls and 0.2912 kO.0781 min-' in cirrhotics) were identical in the two groups. The estimated input of GSH into the circulation calculated as the product of the basal concentration of GSH, k ,~ and Vd amounted to 392 f 100 nmol min-'kg-' in control subjects and 242 f 68 nmol min-l kg-' in cirrhotics (P < 0.01). We conclude that the lower plasma concentrations of GSH in patients with cirrhosis are due to a decreased input of GSH into the circulation rather than an increased peripheral consumption of GSH. Most likely the defect reflects a decreased hepatic production of GSH and may increase the susceptibility of patients with cirrhosis to toxic insults.
Effect of ethanol on glutathione concentration in isolated hepatocytes
The Biochemical journal, 1980
1. Ethanol induces a decrease in GSH (reduced glutathione) concentration is isolated hepatocytes. Maximal effects appear at 20 mM-ethanol. The concentration-dependence of this decrease is paralleled by the concentration-dependence of the activity of alcohol dehydrogenase. 2. Pyrazole, a specific inhibitor of alcohol dehydrogenase, prevents the ethanol-induced GSH depletion. 3. Acetaldehyde, above 0.05 mM, also promotes a decrease in GSH concentration in hepatocytes. 4. Disulfiram (0.05 mM), an inhibitor of aldehyde dehydrogenase, potentiates the fall in GSH concentration caused by acetaldehyde. 5. The findings support the hypothesis that acetaldehyde is responsible for the depletion of GSH induced by ethanol. 6. Methionine prevents the effect of alcohol or acetaldehyde on GSH concentration in hepatocytes.
Biochemical Evaluation of Patients of Alcoholic Liver Disease and Non-alcoholic Liver Disease
Indian Journal of Clinical Biochemistry, 2013
Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls n = 50. Selection criteria-history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired 't' test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) ([2), ALP and GGT compared to controls (P \ 0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (P \ 0.05). This study suggests that De Ritis ratio [2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratio \1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD.
Plasma glutathione S-transferase alpha1-1 levels in patients with chronic liver disorders
Clinica Chimica Acta, 1997
Recent data suggest that plasma levels of the phase II detoxification enzyme glutathione S-transferase alpha may be a sensitive indicator of hepatocellular integrity in acute liver disorders but little information is available in chronic hepatic disorders. Using a newly developed enzyme linked immunosorbent assay, glutathione S-transferase AI-1 (GSTAI-1) levels were measured in 279 plasma samples from patients with chronic liver disorders. Results were categorized as normal or elevated plasma GSTAI-1 and normal or elevated plasma aspartate aminotransferase (AST) levels. In 24 patients with alcoholic liver cirrhosis, plasma GSTAI-1 levels were not significantly different from a group of 350 healthy controls and only one patient (4%) had an elevated GSTAI-1 level while 10 (42%) patients had elevated AST activities. In samples from patients with primary biliary cirrhosis (n = 150), primary sclerosing cholangitis (n = 26) or chronic hepatitis B (n = 79) significantly (P < 0.0001) elevated plasma GSTAI-1 concentrations were detected in 25 (17%), 7 (27%) and 17 (22%) of the samples, respectively. AST activities were increased in a higher percentage of samples in all three disorders: 89%, 88%, and 57%, respectively. Plasma GSTAI-1 and AST levels were significantly correlated (P < 0.005) in the above mentioned disorders but not in alcoholic liver cirrhosis. It is concluded that plasma GSTAI-1 is not a sensitive parameter for the detection of hepatocellular damage in chronic liver disorders.
Abnormal Hepatic Methionine and Glutathione Metabolism in Patients With Alcoholic Hepatitis
Alcoholism: Clinical & Experimental Research, 2004
Background: Abnormal methionine metabolism occurs in animals fed ethanol and in end-stage cirrhotic patients. Expected consequences of these abnormalities include reduced hepatic S-adenosylmethionine and glutathione (GSH) levels, impaired transmethylation, and reduced homocysteine catabolism, resulting in the often-observed hyperhomocystinemia in cirrhotic patients. These parameters have not been examined simultaneously in patients with less advanced alcoholic liver disease. Methods: Six patients hospitalized for alcoholic hepatitis were studied. Plasma was analyzed for homocysteine, methionine, and GSH levels. Liver biopsies diagnosed acute alcoholic hepatitis and underlying fibrosis. Liver specimens were processed for messenger RNA (mRNA) levels and various metabolites and were compared with those of six normal controls. Results: Three patients had cirrhosis, and three had only portal fibrosis. Plasma levels of homocysteine and methionine were increased in two of the three patients with cirrhosis but not in the patients with fibrosis. All patients had markedly lower plasma GSH levels (mean Ϯ SD: 0.27 Ϯ 0.19 M, which is at least 10-fold lower than the normal range). Hepatic S-adenosylmethionine levels were reduced by 50%, whereas methionine, GSH, and cysteine levels were reduced by 70-80%. The mRNA levels of most enzymes involved in methionine metabolism and GSH synthesis were decreased, whereas albumin expression was unchanged. Despite the well known induction of cytochrome P450 2E1 in chronic alcoholics, its mRNA levels were nearly 70% lower in these patients. Conclusions: In alcoholic hepatitis, abnormal hepatic gene expression in methionine and GSH metabolism occurs and often contributes to decreased hepatic methionine, S-adenosylmethionine, cysteine, and GSH levels. It may be important to replenish these thiols in patients hospitalized with alcoholic hepatitis.
PubMed, 2023
Oxidative stress involvement in liver diseases has been extensively studied. A direct assessment of the reactive species incriminated is avoided due to their short lifespan and high cost. For these reasons an inexpensive and easy to perform test for whole body oxidative stress is highly desired. This pilot study was conducted to assess the relationship between γ-glutamyl transferase (GGT) activity and markers of oxidative stress: reduced glutathione (GSH), glutathione peroxidase (GPx) activity and lipid peroxidation in patients with liver cirrhosis due to chronic ethanol consumption and viral hepatitis. Forty-eight patients with alcoholic liver cirrhosis and cirrhosis developed after HBV and HCV infection were included in this study.Blood GSH andGPxand serum GGT and MDAwere assayed and the results were statistically analyzed. The activity of serum GGT was significantly higher in the alcoholic group. The relationship between GGT activity, GSH and MDA levels was different between groups.A strong significant positive correlation between GGT and GSH was noticed for the patients from GGT Q3 and Q4 quartiles in the group of viral liver cirrhosis, while for alcoholics the relationship between GGT and GSH showed the trend for a negative correlation.The values of serum MDA differ significantly between groups (p<0.015); a very significant variation was observed at low levels of GGT activity (p<0.006). Our study demonstrates that the GSH antioxidant defense system is more compromisedin alcoholic cirrhosisand tends to correlate negatively with GGT. Even in its normal range GGT might be an early and sensitive marker of oxidative stress.
Oxidative Stress in Alcoholic Liver Disease
https://www.ijrrjournal.com/IJRR\_Vol.6\_Issue.12\_Dec2019/Abstract\_IJRR005.html, 2019
Background: Alcoholic Liver disease is mainly of three types:-Alcoholic fatly liver; Alcoholic hepatitis; and alcoholic cirrhosis. During the metabolism of alcohol in the liver, produces highly reactive molecules that can destroy vital cell components through a chemical process called oxidation. Oxidative stress increases the rate of production of free radicals hence induces lipid peroxidation. Antioxidants are natural defence mechanism. Existing in our system and these are capable of scavenging the deleterious free radicals. Aims: To study the activity of serum GGT Serum, MDA and GSH in whole blood in the patients with alcoholic liver disease and its comparison with controls and to study the correlation of serum MDA with serum GGT and blood GSH in the patients with alcoholic liver disease. Material And Method: The study was conducted on 50 diagnosed cases of alcoholic liver disease visiting Rajindra Hospital, Patiala and 50 healthy subjects of matched age & sex served as controls and Biochemical Investigations of Serum GGT, Serum MDA and GSH in whole blood were conducted in the department of Biochemistry Govt. Medical College Patiala and the results were statistically analysed. Results: The mean values of serum GGT in study group and control group were 20.80±6.38 and 234.44±204.31(IU/L) respectively (Normal value of GGT 0-50 (IU/L), mean values of serum MDA in study group and control group were 22.00±5.03 and 53.90±11.43(µmol/L) respectively and mean values of blood glutathione in control group and study group were 41.6±4.51 and 18.40±2.39(mg%) respectively the decrease mean blood Glutathione level in study group as compared to mean blood Glutathione level in control group shows statistically significant association (p value < 0.001). Conclusion: Our study shows that there was increased levels of Serum MDA, Serum GGT and decreased levels of blood glutathione in the study group and there was a positive correlation between Serum MDA levels and Serum GGT levels in the study group and there was a negative correlation between serum MDA levels blood glutathione levels in the study group. This correlation predicts that during increased oxidative stress, the GSH was utilized to counter the oxidative stress due to alcoholic liver disease.
Study of Biochemical Markers in Alcoholic Liver Disease: Hospital-Based Case Control Study
Alcoholism is a chronic, progressive and potential cause of liver disease in the western world and it is most common in Nepal. Numerous data are available regarding alcoholic liver disease (ALD) with biochemical and hematologic indicators but very few works have been made in the Nepalese context. Hence, an effort has been made to evaluate the status of biochemical markers in ALD among the Nepalese subjects.166 ALD cases were enrolled in our OPD. Out of total ALD patients, 110 (66.27 %) patients were male and 56 (33.73%) patients were female. ALD patients had significantly low body weight (p<0.05) and low BMI (p<0.05) compared to control. Hyperbilirubinemia and hypoalbuminemia correlate with alcohol intake. Albumin / globulin ratio significantly decreased in ALD. The elevated levels of AST (p<0.001), ALT (p<0.01), ALP (p<0.001), GGT (p<0.001) and AST/ALT ratio > 1 were found with ALD patients respectively. The percentage of hemoglobin and total number of RBC were found to be significantly decreased, whereas mean corpuscular volume (MCV) significantly increased in ALD. The findings of the present study are consistent with previous studies, suggesting that hepatocytes damage causes leak of these enzymes into the circulation. This study concludes that biochemical and hematological parameters is dependable marker of ALD.
BACKGROUND: All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder.Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and A:G ratio. AIM: To study the pattern of Hepatic enzymes after abstinence among alcohol dependent patients MATERIALS AND METHODS: : A prospective study on all patients with alcohol dependence attending de addiction centre.A total of 118 patients have been enrolled in the study. Serum biomarkers SGOT {AST} and SGPT (ALT) were analysed at 0,15,30, 60 90 and 180 days RESULTS: Mean age in years of the study population is 38.5 years. Mean age of alcohol intake is 21.3 years. Mean duration of alcohol intake is 17.2 years The mean value of AST/ALT ratio was found to be 1.09 with a range of 0.59 to 1.62. In the present study the mean AST levels come down with the increase in the duration of abstinence. CONCLUSIONS: Majority of the subjects reached normal range of AST levels after 30 days of abstinence. Nearly 60% of them reached normal ALT levels after 60 days of abstinence. The AST levels will reach earlier to normal levels when compared to ALT levels in abstinence of Alcohol.