scholarly journals Effect of a novel thiazole derivative and its complex with polymeric carriers on the activity of antioxidant enzymes in murine lymphoma cells

2021 ◽  
Vol 15 (4) ◽  
pp. 37-48
Author(s):  
M. V. Popovych ◽  
◽  
Ya. R. Shalai ◽  
S. M. Mandzynets ◽  
N. E. Mitina ◽  
...  

Background. Previous studies have shown a pronounced cytotoxic effect of thiazole derivatives in combination with polymeric carriers on tumor cells. At the same time, the derivatives were not cytotoxic against non-cancerous cells in vitro. It was shown that thiazole derivatives at concentrations of 10 and 50 μM affected the prooxidant and antioxidant systems of lymphoma cells in vitro. The aim of this work was to study the effect of the complex of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) in combination with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th1), poly(PEGMA) (Th3) and poly(PEGMA-co-DMM) (Th5) on the antioxidant defense system of the NK/Ly cell in vitro. Materials and Methods. The experiments were performed on white wild-type male mice with grafted NK/Ly lymphoma. Tumor cells were inoculated into mice intraperitoneally. Ascites was drained from the abdominal cavity of anaesthetized mice with a sterile syringe on the 7th-10th day after inoculation. Investigated compounds BF1, BF1 + Th1 (Th2, Th12), BF1 + Th3 (Th4, Th14), BF1 + Th5 (Th6, Th16) at a final concentration of 10 μM were added to the lymphoma samples and incubated for 10 min; the activity of antioxidant enzymes was determined according to the techniques described previously. Results. It was found that all the studied complexes based on thiazole derivative BF1 and polymeric carriers poly (VEP-co-GMA)-graft-mPEG (Th2, Th12), poly (PEGMA) (Th4, Th14) and poly (PEGMA-co-DMM) (Th6, Th16) at a concentration of 10 μm increased the activity of SOD, while the activity of CAT and GPX were reduced compared to control. Complexes Th2, Th12 and Th4 increased the significance of the BF1 influence on lymphoma cells from P <0.05 to P <0.01. Pure polymeric carriers did not affect the level of the antioxidant defense system enzymes. Conclusions. Thus, it was found that the polymeric carriers in combination with thiazole derivative BF1 increased the significance of thiazole derivative BF1 influence on the activity of the antioxidant defense system of lymphoma cells, while pure polymeric carriers did not affect the activity of SOD, CAT or GPX. The results of this work can be used for further studies of complexes of thiazole derivative and PEG-containing polymeric carriers as potential antitumor drugs.

2021 ◽  
Vol 15 (2) ◽  
pp. 15-24
Author(s):  
M. V. Popovych ◽  
◽  
Ya. R. Shalai ◽  
V. P. Hreniukh ◽  
O. R. Kulachkovskyy ◽  
...  

Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect of thiazole derivative 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]- thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inocu­lation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.


2004 ◽  
Vol 23 (1) ◽  
pp. 9-13 ◽  
Author(s):  
Irfan Altuntas ◽  
Ibrahim Kilinc ◽  
Hikmet Orhan ◽  
Reha Demirel ◽  
Halis Koylu ◽  
...  

Diazinon is one of the most widely used organophosphate insecticides (OPI) in agriculture and public health programs. The aim of this study was to investigate how an OPI, diazinon, affects lipid peroxidation (LPO) and the antioxidant defense system in vitro. For this purpose, two experiments were carried out. In experiment 1, the effects of various concentrations of diazinon on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each diazinon concentration was incubated with a previously prepared erythrocyte samples at +4°C for 0, 60 and 180 min. After incubation, the malondialdehyde (MDA) levels and the activities of SOD, GSH-Px and CAT were determined. In experiment 2, in order to determine the direct effect of diazinon on the activities of SOD, GSH-Px and CAT, the erythrocytes were haemolysed and incubated with the various concentrations of diazinon at +4°C for 0, 60 and 180 min. In experiment 1, MDA levels and the activities of SOD and GSH-Px increased with increasing diazinon concentration and incubation period, but CAT activity remained unchanged. In experiment 2, SOD activity was significantly decreased, and GSH-Px activity was significantly increased. From these results, it can be concluded that in vitro administration of diazinon results in the induction of erythrocyte LPO and changes the activities of antioxidant enzymes, suggesting that reactive oxygen species may be involved in the toxic effects of diazinon.


2017 ◽  
Vol 67 (4) ◽  
pp. 540-550 ◽  
Author(s):  
Nataša Popović ◽  
B. Snežana Pajović ◽  
Vesna Stojiljković ◽  
Ana Todorović ◽  
Snežana Pejić ◽  
...  

AbstractThis study examined the effects of chronic restraint stress (CRS: 2 hours × 14 days) on gene expression of three antioxidant enzymes, copper, zinc superoxide dismutase (SOD 1), manganese superoxide dismutase (SOD 2) and catalase (CAT) in the rat hippocampus. Also, we examined changes in the activities of SOD 1, SOD 2 and CAT in the hippocampus of chronically stressed rats. Investigated parameters were quantifi ed by using real-time RT-PCR, Western blot analysis and assay of enzymatic activity. We found that CRS did not change mRNA and protein levels of SOD 1 and CAT, but increased mRNA and protein levels of SOD 2. However, CRS treatment increased the enzyme activities of SOD 1, SOD 2 and CAT. Our fi ndings indicate that the increased activity of antioxidant enzymes (SOD 1, SOD 2 and CAT) in the hippocampus may be an important adaptive phenomenon of the antioxidant defense system in chronically stressed rats.


2021 ◽  
pp. 72-86
Author(s):  
О. Deren ◽  
◽  
N. Syrovatka ◽  
M. Koryliak ◽  
О. Dobryanska ◽  
...  

Purpose. The aim of the work was to study certain morpho-physiological parameters of carp as a result of additional introduction of a mycotoxin sorbent to a feed with signs of spoilage. Methodology. During 2019–2020, two experiments were conducted in the laboratory. The first one included 7 groups-analogues of age-1+ Nyvky carp, 20 fish in each group, with an average weight of 22.5 g. The control group of fish was fed for 24 days with a compound feed with signs of spoilage, «Mykosorb» was additionally added to the diet of the experimental groups in the amounts of 0.05, 0.1; 0.15; 0.2; 0.25 and 0.4%, respectively. The second group included 4 groups of age-1+ fish, 12 fish in each group, with an average weight of 20.0 g. The diet of the control group was identical to that of the first experiment, and the experimental groups with the addition of 0.05, 0.075 and 0.1% of «Mycosorb», respectively. During the study, optimal conditions for keeping fish were provided. Fish after were measured and weighed at the end of the experiment and their weight gains were analyzed according to generally accepted methods in fish farming. The activity of antioxidant enzymes and the content of lipid peroxidation products depending on the composition of the diet were studied. Findings. The studies used compound feed with signs of spoilage as a result of violation of their storage technology, which identified three groups of toxins: Aflatoxin B1, Zearalenone and Deoxynivalenol. As a result of the first stage of the study, the rates of application of mycotoxin sorbent into the diet of carp at amounts of 0.05 - 0.2% were determined. At the same time, there was no clear proportional pattern of changes in the average weight of fish depending on the amount of introduction of «Mycosorb», the value increased in all experimental groups compared to the control by 0.4 – 15.2%. Muscles of age-1+ fish were found to have higher (p<0,001) catalase activity after application of 0.15% of the test drug by 1.4 times, 0.2% — by 46%, 0.25% — by 69 and 0.4% — by 79%. Superoxide dismutase activity also increased, except for the groups of 0.2, 0.25 and 0.4% of «Mycosorb». There was a tendency of 21.0 and 22.6% decrease in the content of diene conjugates as a result of feeding 0.05 and 0.1% sorbent and some increase as a result of feeding 0.15; 0.2; 0.25 and 0.4% additives. Studies of the next stage showed that addition of «Mykosorb» at the rate of 0.05, 0.075 and 0.1% to the feed, the average weight of age-1+ carp in the experimental groups increased by 45.4; 37.2 and 30.3%, the condition factor — by 41.9; 40.8 and 42.7%, the relative growth rate is 4.3; 5.9 and 4.6 times, respectively. The fish body height to length ratio was lower by 10.3, 7.0 and 7.4% relative to the control group. Addition of 0.05, 0.075 and 0.1% of «Mycosorb» increased resistance of fish due to an increase in the hepatopancreatic activity of antioxidant enzymes: superoxide dismutase by 28.3, 30.5 and 5.0% and catalase by 56.5 (p<0.001), 55.5 (p<0.001) and 46.3% (p<0.05). At the same time, addition of 0.05 and 0.1% of «Mykosorb» increased the content of diene conjugates by 11.3 (p<0.01) and 12.3% (p<0.01), TBC-active products by 19.7 (p<0.05) and 13.2%. Originality. For the first time, the feasibility of addition of the mycotoxin sorbent «Mykosorb» into the feed with signs of spoilage was studied. The effect of feeding age-1+ carp with diets of various compositions on some morpho-physiological parameters of carp in the conditions of model tests was carried out. Practical value. Additional weigh gains and improvements of the antioxidant defense system of the carp organism were observed. The use of «Mykosorb» in carp feeding allows reducing the negative impact of low quality feed on fish body. Key words: carp, feed, feed additives, mycotoxins, sorbent, morphological parameters, growth, antioxidant defense system


2021 ◽  
Author(s):  
Chao Huang ◽  
Xi Peng ◽  
De-Jiang Pang ◽  
Juan Li ◽  
Berit Smestad Paulsen ◽  
...  

A pectic polysaccharide NNLP-I-I from lotus leaves exhibited antioxidant property through regulating Nrf2-mediated intestinal antioxidant defense system, which will be valuable for its further applications on the treatments of intestinal diseases.


2016 ◽  
Vol 60 (1) ◽  
pp. 163-166
Author(s):  
Kamila Dmochowska-Ślęzak ◽  
Małgorzata Dmitryjuk ◽  
Ewa Zaobidna ◽  
Krystyna Żółtowska

Abstract Varroa destructor is a parasitic mite of the Western honey bee. The activity of five antioxidant enzymes of V. destructor were analysed. Glutathione content and total antioxidant status was also evaluated. Our results suggest that antioxidant enzymes constitute the main line of defense against ROS in V. destructor, whereas low-molecular-weight antioxidants play a limited role in the antioxidant system of mites.


2019 ◽  
Vol 234 (9) ◽  
pp. 16348-16356 ◽  
Author(s):  
Ke Wang ◽  
Sunli Hu ◽  
Ben Wang ◽  
Jianle Wang ◽  
Xiangyang Wang ◽  
...  

2019 ◽  
Vol 39 (5) ◽  
pp. 653-661 ◽  
Author(s):  
HR Momeni ◽  
N Eskandari

Background: Cadmium is an environmental pollutant which can induce the overproduction of free radicals while suppressing the antioxidant defense system. Curcumin is considered a free-radical scavenger and a potent antioxidant. This study was conducted to investigate the effect of curcumin on serum antioxidant enzymes and histopathological changes in mice treated with cadmium. Methods: In this experimental study, adult mice were divided into four groups, namely, control, cadmium chloride (5 mg kg−1), curcumin (100 mg kg−1), and curcumin+cadmium chloride. The animals received curcumin 24 h prior to cadmium chloride injection. After 24 h, blood samples were collected and used to assess the levels of malondialdehyde (MDA), antioxidant enzymes activity (catalase, superoxide dismutase, and glutathione peroxidase), total glutathione, total thiol, and hydrogen peroxide. Histopathological evaluation was also performed for testicular tissue. Results: Mice treated with cadmium showed a significant ( p < 0.001) decrease in the activity of antioxidant enzymes, serum amounts of total glutathione and total thiol, and the diameter of seminiferous tubules compared to the control group. This pollutant also significantly ( p < 0.001) increased serum levels of MDA and hydrogen peroxide and the lumen diameter of seminiferous tubules compared to the control group. In the curcumin+cadmium group, curcumin significantly ( p < 0.001) reversed the adverse effects of cadmium, compared to the cadmium group. In addition, curcumin alone significantly ( p < 0.001) increased serum glutathione peroxidase activity and thiol content compared to the control group. Conclusion: Curcumin, as a potent antioxidant, could compensate the adverse effects of cadmium on lipid and protein peroxidation, potentiated serum antioxidant defense system, and ameliorated some morphometrical parameters in the testis of cadmium-treated mice.


Sign in / Sign up

Export Citation Format

Share Document