scholarly journals Sulforaphane Suppresses Sepsis-Mediated Renal Functions in Cecal Ligation and Puncture Mouse Model

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
In-Chul Lee ◽  
Jong-Sup Bae

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. This study was initiated to determine whether SFN could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of SFN treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with SFN resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. SFN treatment also reduced the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α),▢increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggested that SFN protects mice against sepsis-triggered renal injury.

2016 ◽  
Vol 18 (2(66)) ◽  
pp. 52-59
Author(s):  
B.V. Gutyj ◽  
Y. Lavryshyn ◽  
V. Binkevych ◽  
O. Binkevych ◽  
О. Paladischuk ◽  
...  

The article contains the research results of the effect of cadmium chloride on the indexes of enzyme and nonenzyme systems of  antioxidant defense system in young cattle, such as the activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione levels of vitamins A and E. It is established that feeding calves at a dose of toxicant 0.04 mg / kg activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione levels of vitamins A and E in the blood of experimental animals decreased throughout the experiment. The lowest indicators of antioxidant in the blood of young cattle is set on the twenty -fourth day of the experiment, which is associated with increased activation of lipid peroxidation and the balance between antioxidant system and lipid peroxidation intensity. Given the cadmium load of young cattle it is used a new integrated drug with antioxidant action «Metisevit», which includes metifen, sodium selenite and vitamin E wich is founded as stimulating effects on the activity of antioxidant protection. In particular,it is established probable increase in activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione levels, vitamin A and vitamin E in the blood of young cattle, which has performed cadmium stress. These changes occur through comprehensive action components of the drug «Metisevit» that leads to the normalization of metabolic processes and free radical in the body of the bull. The results of the research indicate antioxidant drug «Metisevit» in the application of its young cattle and the validity of his administration to improve the body's antioxidant status of chronic cadmium toxicosis.


2022 ◽  
Vol 20 (4) ◽  
pp. 63-70
Author(s):  
O. V. Smirnova ◽  
V. V. Tsukanov ◽  
A. A. Sinyakov ◽  
O. L. Moskalenko ◽  
N. G. Elmanova ◽  
...  

Background. The problem of gastric cancer remains unresolved throughout the world, while chronic atrophic gastritis (CAG) increases the likelihood of its development by 15 times. In the Russian Federation, the incidence of gastric cancer (GC) is among the highest, with it prevailing among males. One of the leading mechanisms in molecular pathology of membranes is lipid peroxidation (LPO). The severity of oxidative membrane damage depends on concomitant diseases, contributing to emergence and progression of pathological processes and development of cancer. Currently, the problem of LPO is unsolved in biological systems.The aim of this study was to investigate the state of LPO and antioxidant defense system in CAG and GC. Materials and methods. The parameters were studied in 45 patients with CAG and 50 patients with GC. The control group included 50 practically healthy volunteers without gastrointestinal complaints, who did not have changes in the gastric mucosa according to the fibroesophagogastroduodenoscopy (FEGDS) findings.Results. In patients with CAG, an increase in malondialdehyde, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase was found in the blood plasma compared with the control group. In patients with CAG, lipid peroxidation was activated, and the malondialdehyde level increased by 3.5 times relative to normal values. At the same time, the body fought against oxidative stress by increasing the activity of antioxidant enzymes, such as superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase. All patients with GC showed pronounced oxidative stress in the blood plasma in the form of a 45-fold increase in malondialdehyde. The activity of the main antioxidant enzyme superoxide dismutase was reduced in GC. Catalase was activated, which indicated pronounced oxidative stress, significant damage to blood vessels, and massive cell death. Glutathione-related enzymes (glutathione S-transferase and glutathione peroxidase) and the antioxidant protein ceruloplasmin were activated, which also indicated significant oxidative stress and severe intoxication in patients with GC.Conclusion. Depending on the stage and type of cancer, an in-depth study of lipid peroxidation and factors of the antioxidant defense system can be used to correct therapy and prevent cancer and can serve as markers of progression and prognosis in gastric cancer. 


2016 ◽  
Vol 24 (1) ◽  
pp. 96-102 ◽  
Author(s):  
B. V. Gutyj ◽  
S. D. Mursjka ◽  
D. F. Hufrij ◽  
I. I. Hariv ◽  
N. D. Levkivska ◽  
...  

This article presents the results of research on the influence of cadmium loading on the state level of enzymatic and non-enzymatic antioxidant links of the antioxidant defense system of the organisms of young cattle, such as the activity of catalase, superoxide dismutase, glutathione peroxidase, glutathione levels, selenium, vitamins A and E. It was found that feeding bull calves with cadmium chloride at doses of 0.03 and 0.05 mg/kg of body weight helped to reduce both the enzymatic and non-enzymatic link of antioxidant protection (superoxide dismutase 31%, catalase 13%, glutathione peroxidase 23%, reduced glutathione 10%, vitamin A 28%, vitamin E 31%, selenium 20%). Toxic effects of cadmium promotes change in steady-state concentrations of radical metabolites О2–,ОН˙, НО2˙, which, in turn, trigger the process of lipid peroxidation. The lowest level of indicators of antioxidant defense system in the blood of young cattle was registered on the sixteenth and twenty-fourth days of the experiment, which is associated with increased activation of lipid peroxidation and the disturbaance of the balance between the antioxidant system and lipid peroxidation intensity. The activity of the antioxidant defense system in the blood was different for calves fed with cadmium chloride at doses of 0.03 and 0.05 mg/kg of animal mass. The more cadmium chloride in the feed, the lower the activity of the antioxidant defense system of the calves’ organisms was registered. Thus cadmium chloride depresses the antioxidant defense system, which specifically involves lowering the activity of enzymatic links (catalase, superoxide dismutase, glutathione peroxidase) and non-enzymatic links (reduced glutathione, selenium, vitamins A and E).


2020 ◽  
Vol 3 (2) ◽  
pp. 53-59
Author(s):  
K. Y. Leskiv ◽  
B. V. Gutyj ◽  
D. F. Gufriy ◽  
V. I. Khalak ◽  
O. G. Demchuk

The article presents the results of research on the state of the antioxidant defense system of piglets under nitrate-nitrite toxicosis and the action of corrective factors (methionine, phenarone and methyphene). Nitrate-nitrite load in piglets caused inhibition of the activity of enzymes of the antioxidant defense system, that indicates a decrease in the activity of superoxide dismutase, catalase and glutathione peroxidase in the serum of testing animals. The lowest activity of antioxidant enzymes under chronic nitrate-nitrite toxicosis was on the 60th day of the experiment in the serum of piglets of the control group, where accordingly the activity of superoxide dismutase decreased by 14 %, catalase activity – by 18 %, glutathione peroxidase activity – by 12 %. Lipid peroxidation processes are activated in the blood of animals, namely the level of lipid hydroperoxides and diene conjugates increases under the conditions of experimental nitrate-nitrite load. It should be noted that the highest level of lipid peroxidation products in the serum of piglets with chronic nitrate-nitrite toxicosis was on the 60 th day of the testing, and accordingly the content of lipid hydroperoxides increased by 67 % and diene conjugates – by 33 %. Administration of methionine, phenarone and methyphene under nitrate load contributed to the activation of the antioxidant defense system compared to animals in the control group. The use of antioxidant drugs in sick piglets also contributed to the inhibition of lipid peroxidation, as indicated by a decrease in the content of lipid hydroperoxides and diene conjugates in the serum of experimental group. More pronounced antioxidant effect was shown by administrating methyphene. The mechanism of action of phenarone and methyphene is associated with the direct effect of its components on the inhibition of the absorption of metabolites that have a toxic effect on cell membranes of animals. As a result of the adsorbing action of zeolite, which is part of the drugs, in the digestive tract there is a decrease in the concentration of substances that can be substrates for lipid peroxidation, as well as removal of toxic metabolites in the blood, which are prooxidants. This process occurs by osmosis and diffusion of these substances through the capillaries of the microvilli of the small intestine and their subsequent fixation on the sorbent granules.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2773-2773
Author(s):  
Shogo Kasuda ◽  
Hideto Matsui ◽  
Shiro Ono ◽  
Yasunori Matsunari ◽  
Kenji Nishio ◽  
...  

Abstract Sepsis is a serious inflammatory response syndrome, in which systemic activation of both inflammatory and coagulation pathways are provoked by severe microbial infection. In addition to the known hemostatic functions, von Willebrand factor (VWF) is recently assumed to participate in a cross-talk between inflammation and thrombosis. Indeed, recent mouse model studies demonstrated that proper functional regulation of VWF-dependent inflammatory responses by ADAMTS13 considerably improved the disease progression of brain stroke or myocardial infarction. However, little is known about the detailed mechanisms or relevant role of VWF functions in inflammation. We therefore studied the physiologic relevance of VWF-dependent inflammatory responses in a mouse model of experimental sepsis by cecal ligation and puncture (CLP). The mouse CLP was performed according to the established standard protocol (Rittirsch D, et al., Nat Protoc, 2009). Briefly, mouse cecum was ligated distal to the ileocecal valve under laparotomy, punctured with 18 gauge needle and gently pressed until a small drop of stool appeared. The cecum was returned to the peritoneal cavity and 200 μL of saline was injected into the cavity to avoid dehydration before body wall and skin incision were closed with a 4-0 Sofsilk. We compared 17 wild-type (WT) and 17 VWF-gene deleted (knock-out; KO) mice (from The Jackson Laboratory, Bar Harbor, ME), all of which were 10-12 weeks of age, healthy and fertile. Excess blood loss was not observed in all (WT or KO) mice during the CLP operation. Kaplan-Meier analysis revealed the significantly (p < 0.05) lower survival rate of KO mice than that of WT (KO; 23.5% vs. WT; 58.8% at the Day 7 of CLP). The impaired survival rate of KO mice was restored by the bolus administration of human VWF (n=21, 2.5 U/mouse) to an extent comparable to that of WT. Peripheral blood analysis of KO mice at 24 hours after CLP showed the severe leukocytopenia with sharp decrease of neutrophils in blood, as compared to WT. In addition, formation of walled-off abscess was confirmed at the peri-cecal space in all the WT and KO mice alive even at the Day 7 of CLP, while such focal abscess formation was not found in mice died before the Day 3 of CLP. Thus, our results altogether indicate that VWF could play a role on the recruitment or accumulation of neutrophils for microbial killing at the local inflammatory focus. VWF-mediated platelet aggregate formation in peripheral capillary vessels then could shut down the local microcirculation, thereby blocking systemic microbial expansion as a crucial biological defense mechanism. Disclosures Shima: Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Alejandra Zúñiga-Muñoz ◽  
Rodrigo Velázquez Espejel ◽  
Alfredo Cabrera-Orefice ◽  
...  

We report the effect of cross-sex hormonal replacement on antioxidant enzymes from rat retroperitoneal fat adipocytes. Eight rats of each gender were assigned to each of the following groups: control groups were intact female or male (F and M, resp.). Experimental groups were ovariectomized F (OvxF), castrated M (CasM), OvxF plus testosterone (OvxF + T), and CasM plus estradiol (CasM + E2) groups. After sacrifice, retroperitoneal fat was dissected and processed for histology. Adipocytes were isolated and the following enzymatic activities were determined: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). Also, glutathione (GSH) and lipid peroxidation (LPO) were measured. In OvxF, retroperitoneal fat increased and adipocytes were enlarged, while in CasM rats a decrease in retroperitoneal fat and small adipocytes are observed. The cross-sex hormonal replacement in F rats was associated with larger adipocytes and a further decreased activity of Cu-Zn SOD, CAT, GPx, GST, GR, and GSH, in addition to an increase in LPO. CasM + E2exhibited the opposite effects showing further activation antioxidant enzymes and decreases in LPO. In conclusion, E2deficiency favors an increase in retroperitoneal fat and large adipocytes. Cross-sex hormonal replacement in F rats aggravates the condition by inhibiting antioxidant enzymes.


2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Susanne Drechsler ◽  
Katrin M. Weixelbaumer ◽  
Heinz Redl ◽  
Martijn van Griensven ◽  
Soheyl Bahrami ◽  
...  

To simulate and monitor the evolution of posttraumatic sepsis in mice, we combined a two-hit model of trauma/hemorrhage (TH) followed by polymicrobial sepsis with repetitive blood sampling. Anesthetized mice underwent femur fracture/sublethal hemorrhage and cecal ligation and puncture (CLP) 48 h later. To monitor outcome-dependent changes in circulating cells/biomarkers, mice were sampled daily (facial vein) for 7 days and retrospectively divided into either dead (DIE) or surviving (SUR) by post-CLP day 7. Prior to CLP, AST was 3-fold higher in DIE, while all other post-TH changes were similar between groups. There was a significant post-CLP intergroup separation. In SUR, RBC and Hb were lower, platelets and neutrophils higher, and lymphocytes mixed compared to DIE. In DIE, all organ function markers except glucose (decrease) were few folds higher compared to SUR. In summary, the combination of daily monitoring with an adequate two-hit model simulates the ICU setting, allows insight into outcome-based responses, and can identify biomarkers indicative of death in the acute posttraumatic sepsis in mice.


2003 ◽  
Vol 22 (6) ◽  
pp. 423-427 ◽  
Author(s):  
Mary Otsyula ◽  
Matthew S. King ◽  
Tonya G. Ketcham ◽  
Ruth A. Sanders ◽  
John B. Watkins

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosy-lated hemoglobin A1c concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.


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