Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1

2018 ◽  
Vol 63 (1) ◽  
pp. 198-209 ◽  
Author(s):  
Elsayed I. Salim ◽  
Samar F. Harras ◽  
Aisha G. Abdalla ◽  
Mohmmed H. Mona

Abstract Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S. muris infection combined with DMH has significantly increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1 after infection has significantly reduced the ACF numbers particularly larger ones. This inhibition was concomitant with significant inhibition in the immunohistochemical levels of the ki67, Caspase-3 and IgM levels in colorectal epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers levels of superoxide dismutase and catalase as well as the non-enzymatic antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis has significantly modulated the oxidative stress markers in the colorectum, while treatment with Bryostatin-1 has exerted significant curative potential. A mechanism could be explained that Bryostatin-1 treatment has reduced oxidative stress markers activities along with affecting host to parasite immunity possibly leading to changes in the COX-2 and APC expression, retarding cellular proliferation and subsequently reducing the colorectal carcinogenesis events.

2015 ◽  
Vol 309 (8) ◽  
pp. R814-R823 ◽  
Author(s):  
Vladimir V. Matchkov ◽  
Violetta V. Kravtsova ◽  
Ove Wiborg ◽  
Christian Aalkjaer ◽  
Elena V. Bouzinova

Major depression is known to be associated with cardiovascular abnormalities, and oxidative stress has been suggested to play a role. We tested the hypothesis that antidepressant treatment reduces oxidative stress and endothelial dysfunctions in the chronic mild stress (CMS) model of depression in rats. Rats with >30% reduction in sucrose intake after 4 wk of CMS were defined in the study as CMS-susceptible and compared with unstressed controls. Sixteen CMS-susceptible and eight unstressed rats were treated during weeks 5 to 8 of the CMS protocol with escitalopram. Escitalopram-treated rats with >20% recovery in the sucrose consumption during the last 2 wk of treatment were defined as escitalopram responders. Rats that did not reach these criteria were defined as escitalopram nonresponders. In the open field test, escitalopram responders demonstrated anxiolytic effect of treatment. In mesenteric small arteries, escitalopram affected neither NO nor cyclooxygenase-1 (COX-1)-mediated vasodilation. Escitalopram potentiated endothelium-dependent hyperpolarization-like response, which was suppressed in the vehicle-treated CMS-susceptible rats and reduced COX-2-dependent relaxation, which was elevated in the vehicle-treated CMS-susceptible rats. Escitalopram did not affect blood pressure and heart rate, which were elevated in the vehicle-treated CMS-susceptible rats. Oxidative stress markers were changed in association with CMS in liver, heart, and brain. Escitalopram normalized oxidative stress markers in the majority of tissues. This study demonstrates that the antidepressant effect of escitalopram is associated with partial improvement of endothelial function in small arteries affecting COX-2 and endothelium-dependent hyperpolarization-like pathways.


2015 ◽  
Vol 309 (12) ◽  
pp. F1035-F1048 ◽  
Author(s):  
Line Nilsson ◽  
Kirsten Madsen ◽  
Søren Krag ◽  
Jørgen Frøkiær ◽  
Boye L. Jensen ◽  
...  

Renal oxidative stress is increased in response to ureteral obstruction. In vitro, cyclooxygenase (COX)-2 activity contributes to protection against oxidants. In the present study, we tested the hypothesis that COX-2 activity counters oxidative stress and apoptosis in an in vivo model of obstructive nephropathy. Renal oxidative stress markers, antioxidant enzymes, and markers of tubular injury, tubular dilation, and apoptosis were investigated in COX-2 knockout (COX-2−/−) and wild-type (WT) mice subjected to 3 or 7 days of unilateral ureteral obstruction (UUO). In a separate series, WT sham-operated and UUO mice were treated with a selective COX-2 inhibitor, parecoxib. COX-2 increased in response to UUO; the oxidative stress markers 4-hydroxynonenal and nitrotyrosine protein residues increased in kidney tissue with no genotype difference after UUO, whereas the antioxidant enzymes heme oxygenase-1 and SOD2 displayed higher levels in COX-2−/− mice. Tubular injury was aggravated by COX-2 deletion, as measured by tubular dilatation, an increase in kidney injury molecule-1, cortical caspase-3 content, and apoptosis index. In conclusion, COX-2 is necessary to protect against tubular injury and apoptosis after UUO but not necessary to protect against oxidative stress. COX-2 is not likely to directly regulate antioxidant enzymes heme oxygenase-1 and SOD in the kidney.


Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  

Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Shima Fathi ◽  
Mohammad Taghi Goodarzi ◽  
Shiva Borzouei ◽  
Jalal Poorolajal ◽  
...  

Background: One of the most common complications of pregnant women is gestational diabetes mellitus (GDM). Oxidative stress can play an important role in GDM. Objective: The aim of this study was to evaluate salivary antioxidants and oxidative stress markers in GDM. Method: Twenty pregnant women with GDM and 20 healthy pregnant women with normal blood glucose test participated in this study. Five mL of unstimulated saliva samples were collected. Spectrophotometric assay was carried out for sialochemical analysis. Stata software was used for data analysis. Results: The GDM group exhibited no significant difference in salivary total antioxidant capacity and malondialdehyde compared to the healthy control group. All of antioxidants markers, the uric acid, total antioxidant, peroxidase and catalase, decreased in GDM group that the difference of peroxidase and catalase was statistically significant. All of oxidative stress markers, the salivary malondyaldehid, total oxidative stress and total thiol, increased in GDM group. GDM group exhibited significantly higher salivary total oxidative stress levels. Conclusion: Catalase level was significantly lower and total oxidative stress was significantly higher. These two markers might have significant importance and might exhibit early changes compared to other factors in GDM. . Some of salivary antioxidants might have diagnostic, prognostic or therapeutic implications in GDM. Other studies with large sample size on salivary and blood samples need to be done to confirm this properties and salivary samples using instead of blood samples in GDM biomarkers changes.


2020 ◽  
Vol 20 (4) ◽  
pp. 584-590 ◽  
Author(s):  
Shima Fathi ◽  
Shiva Borzouei ◽  
Mohammad Taghi Goodarzi ◽  
Jalal Poorolajal ◽  
Fatemeh Ahmadi-Motamayel

Background: Diabetes Mellitus (DM) is a progressive metabolic disorder. Objective: The aim of this study was to investigate the relationship between antioxidant and oxidative stress markers in the saliva of patients with type 2 DM and a healthy control group. Methods: In this study, 20 patients with diabetes and 20 healthy individuals were evaluated. Salivary antioxidants markers consisted of total antioxidant capacity (TAC), uric acid (UA), peroxidase and catalase. Oxidative stress markers included total oxidant status (TOS), malondealdehyde (MDA) and total thiol (SH). Sialochemical analysis was performed with spectrophotometric assay. All the statistical analyses were conducted using STATA software. Results: TAC decreased significantly in patients with diabetes. Although salivary UA and peroxidase were lower in patients with diabetes compared to the control group, the difference was not significant. Salivary catalase in patients with diabetes was significantly lower than that in the control group. MDA and TOS exhibited significantly higher levels in type 2 DM. SH levels were slightly higher in DM. Conclusions: According to the results of the present study, there were some changes in the salivary levels of some antioxidants and oxidative stress markers in patients with type 2 DM and could be measured as an indicator of serum changes..


2021 ◽  
Vol 65 ◽  
pp. 126711
Author(s):  
Barbara Witt ◽  
Michael Stiboller ◽  
Stefanie Raschke ◽  
Sharleen Friese ◽  
Franziska Ebert ◽  
...  

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