Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes

1989 ◽  
Vol 76 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Antonio Zorzano ◽  
Luis Ruiz del Arbol ◽  
Emilio Herrera

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1. 2. 1. 3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 μmol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH. 6. In summary, our data demonstrate that (a) marked modifications in ADH activity, as found in patients with atypical ADH or in subjects with alcoholic liver disease, are not accompanied by parallel alterations in the kinetics of ethanol disappearance, suggesting that ADH activity per se does not limit ethanol metabolism in vivo, (b) hepatic high-Km ALDH activity is decreased in patients with liver disease independent of alcoholism, and therefore decreased ALDH activity cannot be considered as a primary defect in alcoholism but as a consequence of liver damage, and (c) erythrocyte ALDH does not reflect hepatic high-Km ALDH.

1986 ◽  
Vol 70 (3) ◽  
pp. 295-299 ◽  
Author(s):  
K. Matthewson ◽  
C. O. Record

1. Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects. 2. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P < 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not. 3. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P < 0.05) but not in the other study groups.


1985 ◽  
Vol 69 (5) ◽  
pp. 561-570 ◽  
Author(s):  
E. Barbara Mawer ◽  
H. J. Klass ◽  
T. W. Warnes ◽  
Jacqueline L. Berry

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P < 0.005 and P < 0.05, respectively) but no difference was seen in controls. 2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups. 3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P < 0.02) but concentrations in the two groups were not different. 4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P < 0.05). 5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P < 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005). 6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction. 7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.


2020 ◽  
pp. 182-188
Author(s):  
V. D. Lunkov ◽  
M. V. Maevskaya ◽  
V. T. Ivashkin

Objective of the study. prove the effectiveness of brief psychological intervention (BPI) conducted by an internist in achieving and maintaining abstinence in patients with alcoholic liver disease (ALD).Materials and methods. A total of 65 patients were included in the study: 29 patients in the BPI group and 36 in the historical control group. A comparative analysis of the frequency of achievement and maintenance of abstinence and analysis of factors associated with these parameters were conducted.Results of the study. The frequency of achieving abstinence was significantly higher in the BPI group compared with the control group after 6, 9, 12 and 24 months from the date of inclusion in the study (p <0.001, p = 0.002, p = 0.001, p = 0.017, respectively; criterion χ2). The frequency of failures to achieve abstinence in the CPC group was significantly lower than in the control group after 6 months and in general for the entire observation period (p = 0.004, p = 0.005, respectively; criterion χ2). Provision of BPIs for 12 months after alcohol-induced decompensation serves as a factor that is reliably associated with achieving total abstinence within 24 months (p = 0.001, criterion χ2). Decompensated cirrhosis of the liver serves as factors independently associated with failures to achieve abstinence within 24 months after alcohol-induced illness (OS: 10.72 [95% CI 2.17–52.81]; p = 0.004) and the absence of BPI after discharge from the hospital (OSH BPI: 0.80 [95% CI 0.14–0.479]; p = 0.006)Conclusion. BPIs provided by an internist to the patients with ABD for 12 months after alcohol-induced decompensation leads to a higher rate of achieving total abstinence and decrease in the frequency of failures to achieve abstinence within 24 months after discharge from the hospital.


2018 ◽  
Vol 356 (1) ◽  
pp. 10-14 ◽  
Author(s):  
Binxia Chang ◽  
Shuli Hao ◽  
Longyu Zhang ◽  
Miaomiao Gao ◽  
Ying Sun ◽  
...  

2018 ◽  
Vol 6 (6) ◽  
pp. 232596711877986 ◽  
Author(s):  
Daniel Jandacka ◽  
Jan Plesek ◽  
Jiri Skypala ◽  
Jaroslav Uchytil ◽  
Julia Freedman Silvernail ◽  
...  

Background: Despite the increasing incidence of Achilles tendon (AT) ruptures, there is a lack of information on the possible risks associated with regular running and walking for exercise after an injury. There are some known kinematic gait changes after an AT rupture, especially at the knee. However, it is not clear whether runners with AT ruptures may be at risk for secondary knee injuries during shod or barefoot running/walking. Purpose/Hypothesis: The purpose of this study was to compare the kinematics and kinetics of barefoot walking and barefoot and shod running between athletes with a history of AT ruptures and a healthy control group. We hypothesized that there would be increased knee joint loads in the affected limb of the AT rupture group, especially during shod running. Study Design: Controlled laboratory study. Methods: Ten patients who had undergone surgical treatment of a unilateral acute AT rupture (6.1 ± 3.7 years postoperatively ) and 10 control participants were matched according to age, sex, physical activity, weight, height, and footfall type. The kinematics and kinetics of barefoot walking and barefoot and shod running were recorded using a high-speed motion capture system synchronized with force platforms. Results: The main outcome measures were lower extremity joint angles and moments during the stance phase of walking and running. After AT repair, athletes had increased internal knee abduction moments during shod and barefoot running compared with the healthy control group ( P < .05, η2 > 0.14). There were no significant differences in kinematics and kinetics during walking between the AT rupture and healthy control groups ( P ≥ .05). Conclusion: After an AT rupture, athletes had increased internal knee abduction moments during running compared with the healthy control group. Clinical Relevance: The increased abduction loads on the knee in patients with an AT rupture could lead to further running-related injuries. However, barefoot walking may be used as a proprioceptive exercise without an increased risk of overuse injuries in these patients.


2019 ◽  
Vol 13 (1) ◽  
Author(s):  
Mohammed A. Assiri ◽  
Hadi R. Ali ◽  
John O. Marentette ◽  
Youngho Yun ◽  
Juan Liu ◽  
...  

Abstract Background Chronic alcohol consumption is a significant cause of liver disease worldwide. Several biochemical mechanisms have been linked to the initiation and progression of alcoholic liver disease (ALD) such as oxidative stress, inflammation, and metabolic dysregulation, including the disruption of NAD+/NADH. Indeed, an ethanol-mediated reduction in hepatic NAD+ levels is thought to be one factor underlying ethanol-induced steatosis, oxidative stress, steatohepatitis, insulin resistance, and inhibition of gluconeogenesis. Therefore, we applied a NAD+ boosting supplement to investigate alterations in the pathogenesis of early-stage ALD. Methods To examine the impact of NAD+ therapy on the early stages of ALD, we utilized nicotinamide mononucleotide (NMN) at 500 mg/kg intraperitoneal injection every other day, for the duration of a Lieber-DeCarli 6-week chronic ethanol model in mice. Numerous strategies were employed to characterize the effect of NMN therapy, including the integration of RNA-seq, immunoblotting, and metabolomics analysis. Results Our findings reveal that NMN therapy increased hepatic NAD+ levels, prevented an ethanol-induced increase in plasma ALT and AST, and changed the expression of 25% of the genes that were modulated by ethanol metabolism. These genes were associated with a number of pathways including the MAPK pathway. Interestingly, our analysis revealed that NMN treatment normalized Erk1/2 signaling and prevented an induction of Atf3 overexpression. Conclusions These findings reveal previously unreported mechanisms by which NMN supplementation alters hepatic gene expression and protein pathways to impact ethanol hepatotoxicity in an early-stage murine model of ALD. Overall, our data suggest further research is needed to fully characterize treatment paradigms and biochemical implications of NAD+-based interventions.


1993 ◽  
Vol 84 (1) ◽  
pp. 113-117 ◽  
Author(s):  
N. M. Lowe ◽  
A. Green ◽  
J. M. Rhodes ◽  
M. Lombard ◽  
R. Jalan ◽  
...  

1. The short-term (120 min) kinetics of Zn turnover has been studied in control subjects and patients with alcoholic liver disease after intravenous injection of 0.5 mg of 96.5% enriched 70ZnCl2. 2. The 70Zn enrichment of plasma was found closely to obey two-compartment kinetics and the derived two-component decay equation has been used to calculate the size and turnover of the initial two rapidly exchanging pools of body Zn. 3. In normal subjects isotopic Zn appears initially to equilibrate with the whole of the plasma Zn which comprises the first metabolic compartment, pool a. This has a size of 0.72 ± 0.1 μmol/kg. 70Zn equilibration then occurs with a second compartment, pool b, consistent with a rapidly exchanging liver Zn pool of size 3.60 ± 0.93 μmol/kg. The fractional turnover rate of pool b was found to be fivefold slower than that of pool a. 4. In the alcoholic group an expansion of pool a was observed (1.63 ± 0.39 μmol/kg), but the size of the second pool was not significantly different from that of control subjects (5.55 ± 1.0 μmol/kg), although its fractional turnover was significantly increased (Kab: control subjects, 0.018 ± 0.002 min−1, alcoholic patients, 0.031 ± 0.006 min−1). 5. These data therefore demonstrate that kinetic studies using stable isotopes of Zn can provide novel information on exchangeable Zn pools in man, but provide no support for the possibility of an underlying Zn depletion in patients with alcoholic liver disease.


2020 ◽  
Vol 9 (4) ◽  
pp. e107942900
Author(s):  
Alvaro Gustavo Ferreira da Silva ◽  
Franciscleudo Bezerra da Costa ◽  
Yasmin Lima Brasil ◽  
Brencarla de Medeiros Lima ◽  
Eder Pereira da Rocha Sousa ◽  
...  

Ziziphus joazeiro is endemic to the brazilian Caatinga and its fruits can be used as a food supplement by accelerating the ethanol metabolism in the body and reducing the alcohol harmful effects due to high alcohol dehydrogenase (ADH) activity. The objective was to determine the kinetics of ADH activity, in different incubation times, of Z. joazeiro mature fruits as a food supplement. Ziziphus joazeiro fruits, at the fourth maturation stage, were incubated for 0 (no incubation), 3, 6, 12, 24 and 48 hours at room temperature. The ADH activity was determined. ADH activity was higher in fruits incubated for 0 and 3 h. The ADH activity was higher in the early incubation times, probably due to the greater availability of NAD+, which after being reduced to NADH delayed regeneration. Without the cofactor in the oxidized form, the enzymatic activity decreases. Ziziphus joazeiro fruit has the potential to be used as a food supplement accelerating the alcohol metabolism and reducing the harmful effects.


Author(s):  
Ranjit S. Ambad ◽  
Suryakant Nagtilak ◽  
Gangaram Bhadarge ◽  
Meghali Kaple

Introduction: Alcohol abuse is a global health problem. The liver maintains high muscle damage by over drinking because it is a major source of ethanol metabolism. Among substance abusers, about 35 % develop advanced liver disease because the number of viral mutations increases, slows down, or inhibits the progression of liver disease. Glutathione-S-transferase is a family of Phase II enzyme-releasing toxins that cause the synthesis of glutathione in a variety of chronic and external electrophilic types. GSTs are divided into two very different family members: family members bound by microsomal membrane and cytosolic. Aim: To study the Glutathione S Transferase π and Malondialdehyde in Alcoholic Patients. Materials and Methods: Present study comprises 100 Subjects were included in the study and distributed in two groups. Patients from group one was alcoholic patients, enrolled from medicine ward and 50 non-alcoholic healthy individuals from group two were from non-alcoholic population as well as medicine ward. Results: Rise of GGT, AST and ALT in Alcoholic patients (54.54 ± 3.72, 19.21 ± 0.68 and 24.32 ± 1.27 respectively) as compare to healthy individuals (24.40 ± 3.16, 10.36±0.35 and 17.06±0.84 respectively). The level of GST-π was decreased in alcoholic patients (62.44±26.30) as compare to control group (83.26±32.71). Similarly, the level of MDA was raised in alcoholic patients (5.36 ± 0.51) as compare to healthy individuals (4.73 ± 0.21). Conclusion: Present study suggests that it would be vital to contain SGOT, SGPT, GGT, MDA and GST-π calculation in the prognostic assessment of alcoholic patients.


Sign in / Sign up

Export Citation Format

Share Document