scholarly journals The Prognostic Role of Glutathione and Its Related Antioxidant Enzymes in the Recurrence of Hepatocellular Carcinoma

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4071
Author(s):  
Yung-Fang Hsiao ◽  
Shao-Bin Cheng ◽  
Chia-Yu Lai ◽  
Hsiao-Tien Liu ◽  
Shih-Chien Huang ◽  
...  

The imbalance of high oxidative stress and low antioxidant capacities is thought to be a significant cause of the development and progression of hepatocellular carcinoma (HCC). However, the impact of oxidative stress, glutathione (GSH), and its related antioxidant enzymes on the recurrence of HCC has not been investigated. The purpose of this study was to compare the changes to oxidative stress and GSH-related antioxidant capacities before and after tumor resection in patients with HCC recurrence and non-recurrence. We also evaluated the prognostic significance of GSH and its related enzymes in HCC recurrence. This was a cross-sectional and follow-up study. Ninety-two HCC patients who were going to receive tumor resection were recruited. We followed patients’ recurrence and survival status until the end of the study, and then assigned patients into the recurrent or the non-recurrent group. The tumor recurrence rate was 52.2% during the median follow-up period of 3.0 years. Patients had significantly lower plasma malondialdehyde level, but significantly or slightly higher levels of GSH, glutathione disulfide, trolox equivalent antioxidant capacity, glutathione peroxidase (GPx), and glutathione reductase (GR) activities after tumor resection compared to the respective levels before tumor resection in both recurrent and non-recurrent groups. GSH level in HCC tissue was significantly higher than that in adjacent normal tissue in both recurrent and non-recurrent patients. Decreased plasma GPx (HR = 0.995, p = 0.01) and GR (HR = 0.98, p = 0.04) activities before tumor resection, and the increased change of GPx (post—pre-resection) (HR = 1.004, p = 0.03) activity were significantly associated with the recurrence of HCC. These findings suggest there might be a possible application of GPx or GR as therapeutic targets for reducing HCC recurrence.

2021 ◽  
Vol 11 (8) ◽  
pp. 684
Author(s):  
Yen-Po Lin ◽  
Shu-Hsien Lin ◽  
Chih-Chi Wang ◽  
Chih-Che Lin ◽  
Ding-Wei Chen ◽  
...  

Backgrounds and Aim: Metabolic-associated fatty liver dis-ease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited. Here, we aimed to evaluate the impact of MAFLD on hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. Methods: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed. Results: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719–1.131, p = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518–1.006, p = 0.107) were observed between patients with and without MAFLD in multivariate analysis, the patients with MAFLD tended to achieve better recurrent-free survival compared to patients without MAFLD. Notably, lean MAFLD (BMI < 23 kg/m2) was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117–3.690, p = 0.020) among patients with MAFLD. Conclusions: The overall prognosis in HBV-related early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence. Further studies are warranted to validate these results.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1128-1128
Author(s):  
Yi-Chia Huang ◽  
Chia-Yu Lai ◽  
Shao-Bin Cheng ◽  
Hsiao-Tien Liu ◽  
Shih-Chien Huang

Abstract Objectives Liver cirrhosis is often associated with increased oxidative stress and decreased antioxidant capacities. Vitamin B-6 and glutathione (GSH) are antioxidant nutrients. Inadequate vitamin B-6 status may indirectly limit GSH synthesis and further affect the antioxidant capacities. The purpose of this study was to assess whether individual or the combination of vitamin B-6 and GSH supplementation had effects on antioxidant capacities and clinical outcomes in patients with liver cirrhosis. Methods This was a double-blind randomized clinical trial and a follow-up study. 61 liver cirrhotic patients were randomly assigned to placebo, vitamin B-6 (50 mg pyridoxine/d), GSH (500 mg/d) or B-6 + GSH groups for 12 weeks. After the end of supplementation, 61 patients were followed until the end of the study. Baseline and 12 weeks of fasting blood samples were drawn to measure levels of plasma GSH, oxidized GSH (GSSG), trolox equivalent antioxidant capacity (TEAC), activities of glutathione S-transferase (GSH-St), glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), superoxide dismutase (SOD) and catalase. The severity of liver dysfunction (Child-Turcotte-Pugh score) was evaluated at baseline, 12 weeks after baseline, and the end of the follow-up time. Results The median follow-up time was 984 d, 21 patients were lost of follow-up during follow-up period. After 12 weeks of supplementation, neither vitamin B-6 nor GSH supplementation had effects on indicators of oxidative stress and antioxidant capacities. However, high levels of GSH, GSH/GSSG ratio, and GSH-St activity at baseline (week 0) but not at week 12 had significant effect on low Child-Turcotte-Pugh scores at week 0, week12 and the end of follow-up in all patients after adjusting for potential confounders. Conclusions Although GSH supplementation had no significant effect on reducing oxidative stress and increase antioxidant capacities, the decreased glutathione and its related enzyme activity should be considered by clinicians in the treatment of liver cirrhotic patients. Funding Sources This study was funded by a grant from the Ministry of Science and Technology, Taiwan (MOST 104–2320-B-040–009-MY3) and Taichung Veterans General Hospital, Taiwan (TCVGH-1084601C).


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Shao-Bin Cheng ◽  
Ping-Ting Lin ◽  
Hsiao-Tien Liu ◽  
Yi-Shan Peng ◽  
Shih-Chien Huang ◽  
...  

Vitamin B-6 has a strong antioxidative effect. It would be useful to determine whether vitamin B-6 supplementation had effects on antioxidant capacities in patients with hepatocellular carcinoma (HCC) who had recently undergone tumor resection. Thirty-three HCC patients were randomly assigned to either the placebo(n=16)group or the vitamin B-6 50 mg/d(n=17)group for 12 weeks. Plasma pyridoxal 5′-phosphate, homocysteine, indicators of oxidative stress, and antioxidant capacities were measured. Plasma homocysteine in the vitamin B-6 group was significantly decreased at week 12, while the level of trolox equivalent antioxidant capacity (TEAC) was significantly increased at the end of the intervention period. Vitamin B-6 supplementation had a significant reducing effect on the change of plasma homocysteine (β=-2.4,p=0.02) but not on the change of TEAC level after adjusting for potential confounders. The change of plasma homocysteine was significantly associated with the change of TEAC after adjusting for potential confounders (β=-162.0,p=0.03). Vitamin B-6 supplementation seemed to mediate antioxidant capacity via reducing plasma homocysteine rather than having a direct antioxidative effect in HCC patients who had recently undergone tumor resection. The clinical trial number isNCT01964001, ClinicalTrials.gov.


2017 ◽  
Vol 68 (6) ◽  
pp. 1381-1383
Author(s):  
Allia Sindilar ◽  
Carmen Lacramioara Zamfir ◽  
Eusebiu Viorel Sindilar ◽  
Alin Constantin Pinzariu ◽  
Eduard Crauciuc ◽  
...  

Endometriosis is described as a gynecological disorder characterized by the presence of endometrial tissue outside the uterus; extensively explored because of its increasing incidency, with an indubitable diagnostic only after invasive surgery, with no efficient treatment, it has still many aspects to be elucidated. A growing body of facts sustain oxidative stress as a crucial factor between the numerous incriminated factors implicated in endometriosis ethiopathogeny. Reactive oxygen species(ROS) act to decline reproductive function. Our study intends to determine if an experimental model of endometriosis may be useful to assess the impact of oxidative stress on endometrial cells; we have used a murine model of 18 adult Wistar female rats. A fragment from their left uterine horn was implanted in the abdominal wall. After 4 weeks, a laparatomy was performed, 5 endometrial implants were removed, followed by biochemical tissue assay of superoxide dismutase(SOD) and catalase(CAT). At the end of the experiment, the rats were sacrificed, the implants were removed for histopathological exam and biochemical assay of antioxidant enzymes. The results revealed decreased levels of antioxidant enzymes, pointing on significant oxidative stress involvement.


1993 ◽  
Vol 34 (1) ◽  
pp. 26-29 ◽  
Author(s):  
S. Savastano ◽  
G. P. Feltrin ◽  
D. Neri ◽  
P. da Pian ◽  
M. Chiesura-Corona ◽  
...  

Thirty-three consecutive patients with previously untreated hepatocellular carcinoma (HCC) and 6 patients with recurrent HCC were treated with transcatheter arterial embolization (TAE). The patients were not eligible for surgical resection or percutaneous ethanol injection. TAE was performed with Lipiodol Ultra-Fluid, epidoxorubicin and Gelfoam, with a mean of 1.7 treatments per patient. CT was performed 15 days after TAE. The mean cumulative survival was 14.2 months in patients with previously untreated HCC. The survival of patients stages Okuda I and II did not differ significantly (p > 0.05); tumor size did not affect survival (p > 0.05). Two patients with recurrent HCC died 7.0 and 9.3 months after the diagnosis of tumor recurrence; the remaining 4 patients are still alive with a maximum follow-up of 22.5 months from the diagnosis of HCC recurrence. Ten complications occurred in 8 patients, and were controlled by medical therapy. Eleven patients died during the study; no death was related to TAE. The series was not randomized, but comparison with the natural history of HCC suggests that TAE is effective as palliative treatment of advanced or recurrent HCC.


Poljoprivreda ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 15-24
Author(s):  
Magdalena Matić ◽  
◽  
Rosemary Vuković ◽  
Karolina Vrandečić ◽  
Ivna Štolfa Čamagajevac ◽  
...  

During cultivation, wheat is exposed to several abiotic and/or biotic stress conditions that may adversely impact the wheat yield and quality. The impact of abiotic stress caused by nitrogen deficiency and biotic stress caused by phytopathogenic fungus Fusarium culmorum on biomarkers of oxidative stress in the flag leaf of nine winter wheat varieties (Ficko, U-1, Galloper, BC Mandica, BC Opsesija, Ingenio, Isengrain, Felix, and Bezostaya-1) was analyzed in this study. Hydrogen peroxide concentration and lipid peroxidation level were measured as indicators of oxidative stress, while the antioxidant response was determined by measuring the concentration of phenolic compounds and activities of antioxidant enzymes. Wheat variety and nitrogen treatment had a significant effect on all examined biomarkers of oxidative stress in the flag leaf, while the impact of Fusarium treatment was less pronounced. The most significant impact on the measured stress biomarkers had a low nitrogen level, which mainly increased hydrogen peroxide concentration and lipid peroxidation level and decreased activities of antioxidant enzymes in most varieties. The obtained results were discussed and compared with the previous study in which biochemical analyzes were performed on the wheat spike. There was no significant strong correlation between flag leaf and spike response in the measured parameters, which, in addition to the variety-specific response, also indicates a tissue-specific antioxidant response.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Martina Horvathova ◽  
Zuzana Orszaghova ◽  
Lucia Laubertova ◽  
Magdalena Vavakova ◽  
Peter Sabaka ◽  
...  

We examinedin vitroantioxidant capacity of polyphenolic extract obtained from the wood of oakQuercus robur(QR), Robuvit, using TEAC (Trolox equivalent antioxidant capacity) method and the effect of its intake on markers of oxidative stress, activity of antioxidant enzymes, and total antioxidant capacity in plasma of 20 healthy volunteers. Markers of oxidative damage to proteins, DNA, and lipids and activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were determined in the erythrocytes. We have found anin vitroantioxidant capacity of Robuvit of 6.37 micromole Trolox equivalent/mg of Robuvit. One month intake of Robuvit in daily dose of 300 mg has significantly decreased the serum level of advanced oxidation protein products (AOPP) and lipid peroxides (LP). Significantly increased activities of SOD and CAT as well as total antioxidant capacity of plasma after one month intake of Robuvit have been shown. In conclusion, we have demonstrated for the first time that the intake of Robuvit is associated with decrease of markers of oxidative stress and increase of activity of antioxidant enzymes and total antioxidant capacity of plasmain vivo.


BMC Neurology ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Mansoureh Togha ◽  
Soodeh Razeghi Jahromi ◽  
Zeinab Ghorbani ◽  
Amir Ghaemi ◽  
Pegah Rafiee

Abstract Background In recent years, the role of neuroinflammation and oxidative stress in migraine pathogenesis has achieved considerable interest; however, to date findings are equivocal. Thus, the objective of this study was to investigate biomarkers of oxidative stress in episodic and chronic migraineurs (EM and CM patients) and controls. Methods Forty-four patients with EM, 27 individuals with CM and 19 age-sex-matched controls were enrolled. After collecting data on demographic and headache characteristics, blood samples were collected and analyzed to detect serum levels of oxidative stress biomarkers (malondialdehyde (MDA) and nitric oxide (NO)); total antioxidant capacity using Trolox equivalent antioxidant capacity (TEAC) assay; and antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase-1 (GPx-1)). Results Serum levels of CAT and SOD were significantly lower in the CM group than the EM group and controls. However, serum GPx-1 levels of the CM patients were slightly higher than the EM patients and controls (P-value≤0.001). CM patients had lower mean TEAC values than EM patients and controls. In addition, serum levels of NO and MDA were significantly elevated among subjects with CM compared to EM and control individuals (P-value≤0.001). Pearson correlation analysis revealed negative correlations between the number of days of having headaches per month and serum concentrations of the two antioxidant enzymes CAT (r = − 0.60, P-value< 0.001) and SOD (r = − 0.50, P-value< 0.001) as well as TEAC values (r = − 0.61, P-value< 0.001); however, there were positive correlations between headache days and serum GPx-1 levels (r = 0.46, P-value< 0.001), NO (r = 0.62, P-value< 0.001), and MDA (r = 0.64, P-value< 0.001). Conclusion Present findings highlighted that chronic migraineurs had lower total non-enzymatic antioxidant capacity and higher oxidative stress than episodic migraineurs and control individuals. Although more studies are needed to confirm these data, applying novel prophylactic medications or dietary supplements with antioxidant properties could be promising in migraine therapy.


Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1978
Author(s):  
Chia-Yu Lai ◽  
Shao-Bin Cheng ◽  
Teng-Yu Lee ◽  
Yung-Fang Hsiao ◽  
Hsiao-Tien Liu ◽  
...  

Vitamin B-6 and glutathione (GSH) are antioxidant nutrients, and inadequate vitamin B-6 may indirectly limit glutathione synthesis and further affect the antioxidant capacities. Since liver cirrhosis is often associated with increased oxidative stress and decreased antioxidant capacities, we conducted a double-blind randomized controlled trial to assess the antioxidative effect of vitamin B-6, GSH, or vitamin B-6/GSH combined supplementation in cirrhotic patients. We followed patients after the end of supplementation to evaluate the association of vitamin B-6 and GSH with disease severity. In total, 61 liver cirrhosis patients were randomly assigned to placebo, vitamin B-6 (50 mg pyridoxine/d), GSH (500 mg/d), or B-6 + GSH groups for 12 weeks. After the end of supplementation, the condition of patient’s disease severity was followed until the end of the study. Neither vitamin B-6 nor GSH supplementation had significant effects on indicators of oxidative stress and antioxidant capacities. The median follow-up time was 984 d, and 21 patients were lost to follow-up. High levels of GSH, a high GSH/oxidized GSH ratio, and high GSH-St activity at baseline (Week 0) had a significant effect on low Child–Turcotte–Pugh scores at Week 0, the end of supplementation (Week 12), and the end of follow-up in all patients after adjusting for potential confounders. Although the decreased GSH and its related enzyme activity were associated with the severity of liver cirrhosis, vitamin B-6 and GSH supplementation had no significant effect on reducing oxidative stress and increasing antioxidant capacities.


2019 ◽  
Vol 20 (3) ◽  
pp. 605 ◽  
Author(s):  
Kenji Imai ◽  
Koji Takai ◽  
Tatsunori Hanai ◽  
Atsushi Suetsugu ◽  
Makoto Shiraki ◽  
...  

Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.


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