scholarly journals Glutathione-dependent system in the blood of gastric cancer patients with various tumor histotypes and prevalence of the disease

2021 ◽  
Vol 8 (4) ◽  
pp. 12-22
Author(s):  
I. A. Goroshinskaya ◽  
E. I. Surikova ◽  
E. M. Frantsiyants ◽  
L. A. Nemashkalova ◽  
P. S. Kachesova ◽  
...  

Purpose of the study. Exploring the erythrocyte glutathione system functioning in patients with gastric cancer in a comparative aspect, depending on tumor histotype and disease prevalence.Patients and methods. The study included 89 patients with gastric cancer, divided into 6 groups depending on the histotype of the tumor. Separately, the results of the study were analyzed in patients with T4 status according to TNM and in patients at stage 4. The content of reduced glutathione and the activity of glutathione-dependent enzymes in the erythrocytes of the patients' blood were studied by conventional spectrophotometric methods. Statistical processing of the results was carried out using the Statistika 6.0 software package according to the Student's t-test and the nonparametric Wilcoxon-Mann-Whitney test for two independent samples.Results. An increase in the content of glutathione was revealed in patients with gastric cancer compared with the group without oncopathology. The maximum increase was observed in patients with low-grade adenocarcinoma - by 42.5 %, while in signet ring cell carcinoma (SRCC) there was only a tendency to increase by 17.8 %. Glutathione reductase activity was decreased in adenocarcinoma by 23.4-26.2 % and did not change in SRCC. The activity of the antioxidant enzymes glutathione peroxidase and glutathione transferase was increased in all groups, and especially in SRCC - by 76 % and 23-29 %, respectively. In patients with the T4 status and at stage IV of the process, a lower activity of the studied glutathione-dependent enzymes was revealed in comparison with all other groups of patients.Conclusions. The data obtained indicate a greater functional potential of the glutathione system in SRCC. A significant increase in glutathione transferase activity at a sufficiently high level of reduced glutathione can contribute to the development of treatment resistance in SRCC patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16534-e16534
Author(s):  
Irina A. Goroshinskaya ◽  
Ekaterina I. Surikova ◽  
Elena M. Frantsiyants ◽  
Ludmila A. Nemashkalova ◽  
Polina S. Kachesova ◽  
...  

e16534 Background: The role of oxidative stress in tumor growth and the multifaceted functional significance of glutathione have led to an interest in studying the components of the glutathione-dependent system in gastric cancer (GC), which occupies a leading position in cancer incidence and mortality. The aim of this work was to study the functioning of the glutathione system in the red blood cells of patients with gastric cancer in a comparative aspect depending on the histotype of the tumor and the prevalence of the disease. Methods: The study included 89 patients with GC divided into 6 groups depending on the histotype of the tumor. Separately, the results of the study were analyzed in patients with T4 status according to TNM and in patients with stage IV cancer. The content of reduced glutathione and the activity of glutathione-dependent enzymes were studied by conventional spectrophotometric methods in the red blood cells of patients. Statistical processing of the results was performed using the Statistika 6.0 program with Student’s t-test for two independent groups. Results: An increase in the content of glutathione in patients with GC compared with the group without oncopathology was revealed. The maximum increase was observed in patients with low-grade adenocarcinoma - by 42.5%, while in signet ring cell cancer (SRCC) there was only a tendency to increase by 17.8%. Glutathione reductase activity was reduced in adenocarcinoma by 23.4-26.2% and did not change in SRCC. The activity of the antioxidant enzymes glutathione peroxidase and glutathione transferase was increased in all groups and especially in SRCC - by 76% and 23-29%, respectively. In patients with T4 status and at stage 4 of the process, lower activity of the studied glutathione-dependent enzymes was revealed compared with all other groups of patients. Conclusions: The data indicate a greater functional potential of the glutathione system in SRCC. A significant increase in the activity of glutathione transferase with a sufficiently high level of reduced glutathione contributes to the development of treatment resistance in patients with SRCC.


Author(s):  
O. Taburets ◽  
K. Dvorshenko ◽  
M. Tymoshenko ◽  
V. Vereschaka ◽  
T. Beregova ◽  
...  

The activity of enzymes of the glutathione link of the antioxidant system in rats with experimental full-thickness wound has been studied. It is established that in the serum of rats under the experimental model of the cut wound the level of recovered glutathione and glutathione reductase activity decreased, glutathione peroxidase and glutathione transferase activity increased. All investigated parameters normalized in dynamics after treatment with melanin.


2013 ◽  
Vol 68 (10) ◽  
pp. 26-30
Author(s):  
L. V. Korkotashvili ◽  
S. V. Romanova ◽  
S. A. Kolesov

Aim. To detect changes in the concentration of nitric oxide and its metabolites – nitrites and nitrates in conjunction with the  indices of the glutathione system in  the children with chronic hepatitis В and С.    Patients and methods. In the research took a part 76 patients (boys or girls) with chronic hepatitis В and С aged  from 7 up to 16 years. Nitric oxide and its metabolites  determined by method of V.A. Metel’skaya and N.G. Gumanova; level of  reduced glutathione – the titrimetric analysis; activity of glutathione transferase – the method of spectrophotometry.  Results. The content of nitric oxide and its metabolites– nitrites and nitrates – in serum and urine of children with chronic viral hepatitis В and С have increased. Correlations were revealed between nitric oxide and its metabolites  in serum and urine, as well as between these indices and glutathione system parameters – reduced glutathione concentration and activity of enzymes of glutathione transferase of erythrocytes and plasma. Conclusions. In the children with chronic viral hepatitis В and С the increase of the concentration of  nitric oxide and its metabolites in serum and urine is accompanied by decrease of reduced glutathione concentration and increase of glutathione transferase activity in erythrocytes and plasma. These findings suggest the presence of oxidative stress due to which the therapy should be strengthened by antioxidant effect.


Author(s):  
K. Dvorshchenko ◽  
M. Ashpin ◽  
E. Torgalo ◽  
M. Tymoshenko ◽  
L. Ostapchenko

Increase of content of oxidized glutathione (GSSG) is fixed in blood serum at carrageenan-induced rat paw inflammation, as well as increase of the glutathione transferase activity. Upon the same experimental conditions, the level of reduced glutathione (GSH) and activity of glutathione peroxidase and glutathione reductase were decreased. All above mentioned indices was closer to control values in animals treated simultaneously with сarrageenan and drug on the basis of chondroitin sulfate.


Author(s):  
K. Dvorshchenko ◽  
O. Korotkiy ◽  
D. Grebinyk ◽  
Ye. Torgalo

The goal of this work was the research of chondroitin sulfate prophylactic action on the glutathione system state in rat blood serum during acute joint inflammation. The research was performed on white non-linear pubertal rat males weighting 160-240 grams in compliance to all general ethical principles of animal research. All animals were divided to four experimental groups. The first group – the control: the animals were injected with 0,1 ml of 0,9 % NaCl solution in a right hind leg. The second group – rats were subjected to daily intramuscular injections of 3 mg/kg of chondroitin sulfate in the theurapeutic dose during 28 days. The third group – the animals were subjected to daily doses of 0,1 ml of 0,9 % NaCl solution injected in right hind extremities and starting from 29th day the acute joint inflammation was modelled (the animals were subjected to 0,1 ml of 1% of сarrageenan intramuscular injection in right hind extremities. The fourth group – rats were receiving intramuscular injections of therapeutic dose of 3 mg/kg of chondroitin sulfate for 28 days, and after that the acute joint inflammation was modelled starting from 29th day. 40 animals in all were taking part in the experimental research. The glutathione peroxidase activity was assessed judging from the decrease in GSH amount in the reaction with Ellman reagent. The glutathione peroxidase activity was estimated by the decrease in probe optical density owing to NADPH oxidation. Glutathione transferase activity was estimated by the speed of the conjugate formation between GSH and 1-chloro-2,4-dinitrobemzene. The amount of reduced glutathione was estimated spectrophotometrically using orthophthalic aldehyde. It was established that during the carrageenan-induced inflammation the glutathione peroxidase, glutathione reductase and glutathione reductase activity were reduced, a well as the amount of reduced glutathione, whereas the glutathione transferase activity was increased in comparison to the control. It was shown that under the prophylactic injection of the chondroitin sulfate based preparate to animals with acute joint inflammation the aforementioned parameters were partially stabilized.


Author(s):  
A.V. Demchenko

The purpose of the work is to study a glutathione system (level of reduced glutathione and activity of glutathione-dependent enzymes) in a hemolysate of erythrocytes among the patients with chronic cerebral ischemia (CCI). It was examined 287 patients with CCI and 50 healthy people without any signs of cerebrovascular disease using clinical and neuropsychological, laboratory and instrumental methods of investigation. It was established a significant decrease of the reduced glutathione concentration, the decrease of glutathione reductase and glutathione peroxidase and the increase of glutathione transferase activity in a hemolysate of erythrocytes among the patients with chronic cerebral ischemia in comparison with these rates among healthy people. It was established a negative correlated connection between the level of the reduced glutathione, the age of the patients (r=-0,34, р<0,0001), the stage of discirculatory encephalopathy (DE) (r=-0,50, р<0,0001), intima media complex thickness of carotid arteries (r=-0,29, р=0,009), the level of homocysteine (r=-0,81, р<0,0001) and also the level of glutathione peroxidase, the stage of DE (r=-0,39, р<0,0001) and homocysteine level (r=-0,60, р<0,0001).


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15098-e15098
Author(s):  
Ji Soo Park ◽  
Minkyu Jung ◽  
Hye Ryun Kim ◽  
Sun Young Rha ◽  
Hyun Cheol Chung ◽  
...  

e15098 Background: HER2-based therapy was found to improve survival outcome of patients with HER2-positive advanced gastric cancer. In gastric cancer, HER2 overexpression is commonly defined as IHC 3+ or IHC 2+/FISH amplification. Because positivity of HER2 overexpression is reported in below 20%, identifying the predictive clinical factors for the HER2 overexpression before the pathologic analysis may be helpful and cost-effective. Methods: From JAN 2005 to DEC 2010, 517 gastric cancer patients performed with HER2 IHC and/or FISH tests at Yonsei University College of Medicine were enrolled. Results: Among the 517 patients, 61 patients (11.8%) were confirmed as HER2 overexpression. Forty three out of stage IV, 258 patients (16.7%) and 18 out of 259 (6.9%) localized gastric cancer patients had HER2 overexpression (p <0.001). HER2 overexpression was more common in male (14.2% vs. 7.5% in female, p-value 0.024), moderately differentiated (26.4% vs. 11.1%, 8.9%, 4.9% and 5.9% in well differentiated, poorly differentiated, signet ring cell, and mucinous, retrospectively, p <0.001). Patients with elevated CEA (> 5.0 ng/mL vs. ≤ 5.0 ng/mL: 24.3% vs. 8.4%, p <0.001), metastasis to distant lymph node (with vs. without: 28.6% vs. 14.8%, p-value 0.042), without carcinomatosis (without vs. with: 21.2% vs. 11.6%, p-value 0.039) and pulmonary metastasis (with vs. without: 47.4% vs. 14.2%, p <0.001) also frequently had HER2-positive disease. In addition, high risk patients with 4 or more of the 7 features (metastatic disease, male, moderate differentiated adenocarcinoma, elevated CEA level, metastasis to distant lymph node, pulmonary metastasis, and without carcinomatosis) had 32.9% of HER2 positivity. (p <0.001). Conclusions: Those clinicopathologic factors may be helpful to predict the high likelihood of HER2 positive cases prior to pathologic confirmation in gastric cancer. Further molecular study for the HER2 overexpression is needed to clarify and explain this clinical phenomenon.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15512-e15512
Author(s):  
Elena V. Shalashnaya ◽  
Irina A. Goroshinskaya ◽  
Ekaterina Igorevna Surikova ◽  
Dar'ja E. Medvedeva ◽  
Polina S. Kachesova ◽  
...  

e15512 Background: The aim was a comparative study of glutathione system of tumor and its peritumoral tissues at gastric signet ring cell carcinoma (SRCC) and gastric adenocarcinoma (AC) to identify pathogenetic features of malignancy. Methods: Content of reduced glutathione (GSH) and the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione transferase (GST) were determined in the samples of tumor and peritumoral tissues, obtained during the surgery in 21 primary patients: 13 patients with SRCC, 8 patients with AC (G2-G3) without preoperative therapy. Tissue of intact stomach was studied in 12 randomly bereaved. Results: In the AC tumor tissue the GSH level was decreased by 43% and the activity of GPx and the GST was increased by 121.7% and 44.3% (p < 0.05–p < 0.001) compared with intact stomach. In peritumoral tissue both the level of GSH and GPX activity were less than in the tumor tissue at 40-45% (p < 0.05–p < 0.01). In SRCC both the GSH level and the activity of GPx and GST were increased in tumor tissue by 78%, 93.6% and 49.5% (p < 0.05–p < 0.001) compared with the intact stomach. In peritumoral tissue the GSH level was lower than in the tumor tissue by 60.2% (p < 0.01), the enzymes activity was unchanged remaining higher than in the intact stomach. The GSH level both in tumor and in peritumoral tissues was 2-3 folds higher in gastric SRCC than in AC. No significant differences in the activity of glutathione-dependent enzymes in tumors of different histotype were revealed. Conclusions: The results show the differences in the functioning of the glutathione system, depending on the histological type of gastric tumors. It is possible that greater activity of glutathione-dependent system in tissue of SRCC is needed to maintain its increased proliferative activity and determines the features of the biological behavior of this tumor histotype.


2021 ◽  
Vol 102 (2) ◽  
pp. 199-205
Author(s):  
G R Kuramshina ◽  
F Kh Kamilov

Aim. To study changes in the glutathione system in bone tissue during chronic intoxication with elements contained in copper-zinc pyrite ore and antioxidant vitamin administration. Methods. 36 mature male white rats were divided into three groups (control, comparison, experimental). The rats of the experimental and comparison groups received intragastrically copper-zinc pyrite ore powder in a 2% starch solution as a suspension at a dosage of 60 mg/100 g bodyweight daily for three months. During the last month, the experimental group received an antioxidant vitamin preparation (the complex of vitamins with a trace element) containing -tocopherol, -carotene, ascorbic acid and selenium. The content of reduced glutathione, free thiol groups in proteins, the activity of glutathione peroxidase, glutathione transferase, glutathione reductase, gamma-glutamyl transferase, and glucose-6-phosphate dehydrogenase were determined in homogenates derived from femoral epiphysis. The statistical analysis of the results was performed using Statistica 6.0 software. The median (Me) and percentiles (Q1 and Q2) were calculated, a non-parametric MannWhitney U test was carried out to compare study groups. Results. Chronic intoxication with elements contained in copper-zinc pyrite ore causes impairment of the glutathione system in bone tissue. Intoxicated rats showed a decrease in the reduced glutathione content to 71.9% (р=0.014) and free sulfhydryl groups of proteins to 77.8% (р=0.0143), inhibition of glutathione-dependent antioxidant enzymes activities, and disruption of the glutathione reduction system in tissues, compared to the control group. Antioxidant vitamin administration increased the levels of reduced glutathione and free thiol groups of proteins, activated the enzymes involved in the glutathione system: the reduced glutathione content increased to 94.8% (p=0.2132), glutathione peroxidase activity to 85.7% (p=0.0432), glutathione transferase up to 94.3% (p=0.5251), glutathione reductase up to 86.1% (p=0.0442) compared to the control group. Conclusion. Chronic intoxication with metals contained in copper-zinc pyrite ore leads to decreasing the content of reduced glutathione and free thiol groups of proteins in bones along with reducing glutathione reductase and glucose-6-phosphate dehydrogenase activities, inhibition of glutathione peroxidase and glutathione transferase; an antioxidant vitamin administration increases the activity of glutathione reduction enzymes in bone tissue, the content of reduced glutathione and free sulfhydryl groups of proteins, the activities of glutathione peroxidase and glutathione transferase.


1990 ◽  
Vol 45 (1-2) ◽  
pp. 96-106 ◽  
Author(s):  
Samuel P. Yenne ◽  
Kriton K. Hatzios

The influence of the oxime ether safeners, oxabetrinil and CGA-133205, on glutathione content, glutathione reductase (EC 1.6.4.2), and glutathione-S-transferase (EC 2.5.1.18) activity in seeds and seedlings of grain sorghum (Sorghum bicolor (L.) Moench. var. Funk G-522-DR) was investigated. Plant material for these experiments was derived from seed that was either untreated, or treated with 1.25 or 0.4g ai/kg seed of oxabetrinil or CGA-133205, respectively. Measurements were conducted at 0, 1, 2, 4, 8 , 12, 24, 36, and 72 h after the initiation of germination. In safener-treated sorghum seeds, the levels of total and reduced glutathione decreased gradually after the initiation of germination reaching a low at 8 to 12 h and then increased continuously reaching a maximum at 48 h. The greatest increases in glutathione levels were observed in oxabetrinil-treated sorghum seedlings. Glutathione reductase activity was consistently higher in untreated seeds of grain sorghum for the first 24 h of imbibition, but at 36 to 72 h glutathione reductase activity increased in the safener-treated tissues. CGA-133205 appeared to have a greater stimulatory influence on the activity of glutathione reductase than did oxabetrinil. For the first 8 h after germination was initiated, glutathione-S-transferase activity in oxabetrinil- and CGA-133205-treated seeds remained enhanced compared to that of untreated seeds, but was at or below the levels of the activity of glutathione-S-transferase extracted from untreated seeds for the remainder of the experiment. Non-enzymatic conjugation of metolachlor with reduced glutathione increased as the pH of the reaction solution increased from 6.0 to 8.0. Oxabetrinil at 1 to 40 μM and CGA-133205 at 1 to 160 μm enhanced nonenzymatic conjugation of m etolachlor with glutathione. At 80 and 160 |j.m , oxabetrinil reduced the am oun t of non-enzym atic conjugation of metolachlor. Oxabetrinil conjugated with reduced glutathione at low rates either enzymatically or non-enzymatically at pH 8.0 while CGA-133205 did not at any pH. In the presence of metolachlor, the amount of non-enzymatic conjugation of oxabetrinil was decreased, indicating that metolachlor is more reactive towards glutathione than is oxabetrinil. Overall, these data suggest that during the early stages of seed germination and seedling development of grain sorghum , oxim e ether safeners can enhance the detoxication of the herbicide, metolachlor, through enzymatic or non-enzymatic conjugation to reduced glutathione by enhancing either the level of reduced glutathione and/or the activity of glutathione-related enzymes.


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