Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression

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.

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A Natural Phenolic Compound Quercetin Showed the Usefulness by Targeting Inflammatory, Oxidative Stress Markers and Augment 5-HT Levels in One of the Animal Models of Depression in Mice

Drug Research ◽

10.1055/a-0748-5518 ◽

2018 ◽

Vol 69 (07) ◽

pp. 392-400 ◽

Cited By ~ 2

Author(s):

Khadeeja Khan ◽

Abul Kalam Najmi ◽

Mohd Akhtar

Keyword(s):

Oxidative Stress ◽

Phenolic Compound ◽

Open Field ◽

Antidepressant Drugs ◽

Field Tests ◽

Mild Stress ◽

Oxidative Stress Markers ◽

Behavioral Tests ◽

Stress Markers ◽

Immobility Time

Abstract Aim In the present study quercetin was studied for its role in inflammation, oxidative stress markers and 5-HT levels in unpredictable chronic mild stress (UCMS) animal model of depression. Materials and Methods The mice were randomized into different groups trained for UCMS protocol followed by different drug treatments. Treatments were started after 2 weeks from the start of UCMS protocol and continued up to 6 weeks. The behavioral tests such as modified forced swimming (MFST), tail suspension (TST) and open field tests were performed on week 6, at least 24 h after the last drug treatment. Behavioral tests were preceded following animal sacrifice for biochemical estimations. Results A significant decrease in swimming, climbing times and increase in immobility time in MFST and TST was observed in UCMS group. Administration of quercetin (25 mg/kg per orally (p.o) reversed these times in MFST and TST. A decrease in no. of field crossing, time spent in centre and no. of rearing were observed in UCMS group. Quercetin reduced these observations in open field test. There was a decrease in superoxide dismutase (SOD), glutathione (GSH), catalase and 5 HT levels in the brain tissue. Quercetin treatment significantly augmented SOD, GSH, catalase and 5 HT levels. Glutamate, TNF-α and IL-6 levels were increased in UCMS group while quercetin decreased these cytokines. Conclusion Quercetin resulted antidepressant-like effect by its antioxidant, anti-inflammatory activities, reduced excitotoxicity and augmented 5 HT levels. This pointed out the usefulness of this phenolic compound as adjuvent drug along with other antidepressant drugs.

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Effect of sitagliptin on depression in male wistar rats

International Journal of Basic & Clinical Pharmacology ◽

10.18203/2319-2003.ijbcp20195787 ◽

2019 ◽

Vol 9 (1) ◽

pp. 200

Author(s):

Vidya M. Mahalmani ◽

Anil P. Hogade ◽

Sanjay K. Mishra

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Wistar Rats ◽

Cytokine Gene Expression ◽

Antidepressant Effect ◽

Oxidative Stress Markers ◽

Cytokine Gene ◽

Stress Markers ◽

Group I ◽

Male Wistar Rats

Background: Growing evidence supports relationship between depression and inflammation. The hypothesis of involvement of inflammatory pathways in depression is supported by the findings of increased levels of proinflammatory cytokines. So, we decided to evaluate the effect of sitagliptin on depression using forced swim test (FST) and possible effects of sitagliptin on serum oxidative stress markers and cytokine gene expression in rat hippocampus.Methods: FST model was used to evaluate antidepressant effect in male wistar rats. Rats in group I (control group) were given normal saline, group II (standard group) were given fluoxetine, group III and IV (test groups) were given sitagliptin 5 mg/kg and sitagliptin 9 mg/kg respectively. All the drugs in all groups were given per orally. At the end, animals were sacrificed and blood was collected. Hippocampus of rat brain was dissected out. Serum oxidative stress markers and hippocampal pro inflammatory cytokine gene expression analysis was carried out.Results: Sitagliptin 5 mg/kg and 9 mg/kg showed reduction in depressive symptoms and hippocampal cytokine gene expression in comparison to control. In case of serum oxidative stress markers, there was statistically significant reduction in nitric oxide levels with stagliptin 9 mg/kg. Although there was a decrease in the levels of catalase and increase in the levels of glutathione with standard and test groups, the results were not statistically significant.Conclusions: The present study showed significant antidepressant effect activity of standard and test groups. Hence, further research should be carried out to substantiate above results.

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Curcumin Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behaviors via Restoring Changes in Oxidative Stress and the Activation of Nrf2 Signaling Pathway in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/9268083 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Dehua Liao ◽

Chuanfeng Lv ◽

Lizhi Cao ◽

Dunwu Yao ◽

Yi Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathway ◽

Antidepressant Effect ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Spine Density ◽

Related Protein ◽

Stress Markers ◽

Dendritic Length ◽

Nrf2 Signaling Pathway

Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.

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S-allyl Cysteine, a Garlic Compound, Produces an Antidepressant-Like Effect and Exhibits Antioxidant Properties in Mice

Brain Sciences ◽

10.3390/brainsci10090592 ◽

2020 ◽

Vol 10 (9) ◽

pp. 592

Author(s):

Elizabeth Ruiz-Sánchez ◽

José Pedraza-Chaverri ◽

Omar N. Medina-Campos ◽

Perla D. Maldonado ◽

Patricia Rojas

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Forced Swim Test ◽

Antioxidant Properties ◽

Free Radical Scavenger ◽

Antidepressant Effect ◽

Radical Scavenger ◽

Oxidative Stress Markers ◽

Sod Activity ◽

Stress Markers

Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.

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Disruption of cyclooxygenase type 2 exacerbates apoptosis and renal damage during obstructive nephropathy

AJP Renal Physiology ◽

10.1152/ajprenal.00253.2015 ◽

2015 ◽

Vol 309 (12) ◽

pp. F1035-F1048 ◽

Cited By ~ 14

Author(s):

Line Nilsson ◽

Kirsten Madsen ◽

Søren Krag ◽

Jørgen Frøkiær ◽

Boye L. Jensen ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Heme Oxygenase ◽

Ureteral Obstruction ◽

Obstructive Nephropathy ◽

Heme Oxygenase 1 ◽

Oxidative Stress Markers ◽

Tubular Injury ◽

Stress Markers ◽

Cox 2

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.

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

Acta Parasitologica ◽

10.1515/ap-2018-0023 ◽

2018 ◽

Vol 63 (1) ◽

pp. 198-209 ◽

Cited By ~ 5

Author(s):

Elsayed I. Salim ◽

Samar F. Harras ◽

Aisha G. Abdalla ◽

Mohmmed H. Mona

Keyword(s):

Oxidative Stress ◽

Cellular Proliferation ◽

Significant Inhibition ◽

Aberrant Crypt Foci ◽

Colorectal Carcinogenesis ◽

Oxidative Stress Markers ◽

Bryostatin 1 ◽

Stress Markers ◽

Syphacia Muris ◽

Cox 2

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.

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