scholarly journals Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 162
Author(s):  
Renáta Szabó ◽  
Zsuzsanna Szabó ◽  
Denise Börzsei ◽  
Alexandra Hoffmann ◽  
Zelma Nadin Lesi ◽  
...  

Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity were measured. Two weeks of low dose rimonabant treatment significantly reduced the cardiac ROS via boosting of the antioxidant defense mechanisms as regards the HO system, and the SOD and glutathione content. Consistently, the age-related inflammatory response was alleviated. Rimonabant-treated animals showed significantly decreased NF-κB, TNF-α, and MPO levels. Our findings prove the beneficial involvement of CB1 receptor blocker rimonabant on inflammatory and oxidative damages to the aging heart.

2018 ◽  
Vol 44 (4) ◽  
pp. 530-538
Author(s):  
Aysun Çetin ◽  
İhsan Çetin ◽  
Semih Yılmaz ◽  
Ahmet Şen ◽  
Göktuğ Savaş ◽  
...  

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.


2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Mustafa Yalçın ◽  
Muhammed Ali Kıyak ◽  
Mesut Akarsu ◽  
Aslı Çelik ◽  
Göksel Bengi ◽  
...  

Due to the lack of effective medical treatment for non-alcoholic steatohepatitis (NASH), we aimed to evaluate new treatment options. In particular, our goal was to investigate and compare the effects of N-acetylcysteine (NAC) and Adalimumab treatment on tumor necrosis factor alpha (TNF-α) and oxidative stress during the development of NASH in a rat model of the disease. Our study included a total of 35 female Wistar albino rats that were divided into 5 groups of 7 each, and evaluated over a 6 week period. One group received a normal diet, while the other four groups received a methionine and choline deficient (MCD) diet. One of the groups receiving the MCD diet did not take any medicine, while the other three were administered NAC, adalimumab, or a NAC/adalimumab combination therapy. NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received therapy. Even though adalimumab significantly enhanced suppression of TNF-α, the NASH score was suppressed to a more statistically significant extent in the groups receiving NAC. Our study showed that TNF-α and oxidative stress play an important role in NASH pathogenesis. The antioxidant agent, NAC, was found to be superior to the anti-TNF agent, Adalimumab, in the improvement of total NASH score. Although these drugs did not prevent the development of NASH, it was shown that they mildly reverse the NASH histopathology score, suggesting improvement of and overall liver function.


2020 ◽  
Vol 14 (5) ◽  
pp. 155798832093973
Author(s):  
Wiktoria Kurkowska ◽  
Agnieszka Bogacz ◽  
Marta Janiszewska ◽  
Ewa Gabryś ◽  
Michał Tiszler ◽  
...  

Infertility is among the most serious medical problems worldwide. Male factors contribute to 40%–50% of all infertility cases, and approximately 7% of men worldwide are affected by infertility. Spermatozoa are extremely vulnerable to oxidative insult. Oxidative stress results in axonemal damage and increased midpiece sperm morphological defects, which lead to reduced sperm motility. The aim of the study is to evaluate the association between sperm motility and the levels of selected antioxidants, cytokines, and markers of oxidative damage in the seminal plasma. The study group included 107 healthy males, who were split into two subgroups based on the percentage of motile spermatozoa after 1 hr: low motility (LM, n = 51) and high motility (HM, n = 56). The glucose-6-phosphate dehydrogenase (G6PD) activity was 52% lower in the LM group compared to that in the HM group. The level of malondialdehyde (MDA) was 12% higher in the LM group compared to that in the HM group. Similarly, the median values of interleukin (IL)-1β, IL-10, IL-12, and tumor necrosis factor alpha (TNF-α) were higher in the LM group than those in the HM group. Results of the present study revealed that the percentage of motile spermatozoa after 1 hr correlated positively with the levels of IL-1β, IL-10, IL-12, and TNFα. The lower motility of spermatozoa in healthy men is associated with a decreased activity of G6PD and increased levels of cytokines, which may be related to increased oxidative stress in seminal plasma that manifests as an increased level of MDA.


Author(s):  
Farouk Kamel Elbaz ◽  
Hanan F Aly ◽  
Wagdy Kb Khalil ◽  
Gamila H Ali ◽  
Hoda F Booles

ABSTRACTObjective: The present study was conducted to investigate the role of Haematococcus pluvialis extract against oxidative damage, the inflammatory,and apoptotic impacts characterizing the neurodegenerative disorders.Methods: Oxidative stress, B-cell lymphoma 2, brain-derived neurotrophic factor, the inflammation, apoptotic and antiapoptotic impacts in Alzheimer’sdisease (AD) rats were determined through assessment of glutathione reduced (GSH), GSH peroxidase (GPx), lipid peroxide (malondialdehyde), thecytokines level such as tumor necrosis factor-alpha (TNF-α), interleukins (IL-6 and IL-1β), and macrophage inflammation protein (MIP1α) in AD rats.Moreover, the expression of phosphoinositide 3-kinase (PI3K) and serine-threonine protein kinase (Akt) genes regulating the apoptosis in AD ratswas measured.Results: The results revealed that levels of TNF-α, IL-6, IL-1β, and MIP1α were significantly increased in AD rats. Moreover, the expression of PI3Kand Akt genes was downregulated which it was coincided with the increase of apoptosis in AD rats. On the other hand, treatment of AD rats withH. pluvialis extract decreased the oxidative stress of AD in the form of prevention the inflammatory and apoptotic impacts.Conclusion: H. pluvialis could be used for ameliorating AD due to its role in decreases the oxidative stress of AD in the form of prevention theinflammatory and apoptotic impacts. H. pluvialis is a very attractive candidate for uses against neurodegenerative disorders that are caused byincreases oxidative stress inducing neuroinflammation and apoptosis.Keywords: Haematococcus pluvialis, Oxidative stress, Inflammation biomarkers, Apoptotic and antiapoptotic impacts.


2006 ◽  
Vol 74 (3) ◽  
pp. 1916-1923 ◽  
Author(s):  
Chiang W. Lee ◽  
Soumaya Bennouna ◽  
Eric Y. Denkers

ABSTRACT Toxoplasma gondii-infected macrophages are blocked in production of the proinflammatory cytokines interleukin-12 (IL-12) and tumor necrosis factor alpha (TNF-α) upon activation with lipopolysaccharide (LPS). Here, we used pathway-focused cDNA arrays to identify additional T. gondii-regulated transcriptional responses. Parasite infection decreased 57 (inclusive of IL-12 and TNF-α) and increased expression of 7 of 77 LPS-activated cytokine and cytokine-related genes. Interestingly, we found that the LPS-induced transcriptional response of the anti-inflammatory cytokine IL-10 was synergistically increased by T. gondii, results that we validated by conventional reverse transcription-PCR and enzyme-linked immunosorbent assay. Importantly, although the parasite exerted disparate effects in LPS-signaling leading to TNF-α versus IL-10 production, both responses required functional Toll-like receptor 4. We suggest that these effects represent parasite defense mechanisms to avoid or delay induction of antimicrobial activity and/or T-cell-mediated immunity during Toxoplasma infection.


Biologia ◽  
2007 ◽  
Vol 62 (3) ◽  
Author(s):  
Albena Alexandrova ◽  
Elena Bandžuchová ◽  
Anton Kebis ◽  
Marián Kukan ◽  
Daniel Kuba

AbstractCopper is known to induce oxidative stress in a number of models. It was shown that many pathophysiological events were associated with oxidative stress. Further, oxidative stress can increase gene expression of cytokines and of metalloproteinases. We previously found that copper toxic effects in isolated perfused rat livers were associated with significant oxidative stress (as assessed by lipid peroxidation, protein oxidation and oxidative DNA damage, particularly at concentration of 0.03 mM of Cu2+ in the perfusate). Here we investigated gene expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10); matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in frozen liver tissue samples by the real-time PCR assay. Compared to controls, copper at concentration of 0.01 mM did not affect gene expression of TNF-α, IL-10, MMP-2 and MMP-9, whereas copper at concentration of 0.03 mM significantly decreased gene expression of all the four TNF-α, IL-10, MMP-2 and MMP-9 by 69%, 81%, 43%, and 62%, respectively. These results suggest that copper-induced oxidative stress in the isolated rat liver can lead to the suppression of gene expression. Because TNF-α and metalloproteinases are involved also in liver regeneration, the suppression of these genes by copper may be one of the mechanisms by which acute intoxication of animals and humans with copper may impair regenerative capability of the liver.


1998 ◽  
Vol 5 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Ulrich Sack ◽  
Ullrich Burkhardt ◽  
Michael Borte ◽  
Hiltrud Schädlich ◽  
Kerstin Berg ◽  
...  

ABSTRACT Serum cytokine levels were measured in 275 healthy children of different ages (3 to 17 years). Interleukin-1 receptor antagonist (IL-1RA), soluble IL-2R (sIL-2R) (sCD25), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), soluble TNF receptor type II (sTNF-RII) (sCD120b), gamma interferon (IFN-γ), soluble intercellular adhesion molecule 1 (sICAM-1) (sCD54), soluble E selectin (sE-selectin) (ELAM-1; sCD62E), sCD14, and neopterin were measured with commercial test kits. The mean levels of IL-1RA, sIL-2R, TNF-α, sICAM-1, sE-selectin, and sCD14 were higher than in healthy adults. In contrast, IFN-γ and IL-8 were hardly detectable in children and thereby significantly lower than in adults. In the case of TNF-α, sICAM-1, sE selectin, and sCD14, there was a high interindividual variability, apparently unrelated to disease. The profiles of some cytokines, i.e., IL-1RA, IL-6, and TNF-α, showed age-related increases that overlapped with known patterns of physical growth. Of note, sIL-2R and sE-selectin instead declined with time. Because of the remarkable age-dependent variability in healthy pediatric subjects, disease-related changes, as well as therapy-dependent alterations, should be considered with caution.


Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1199 ◽  
Author(s):  
Adriana Cӑtoi ◽  
Alina Pârvu ◽  
Andra Andreicuț ◽  
Aurel Mironiuc ◽  
Alexandra Crӑciun ◽  
...  

Metabolically heathy obesity is characterised by the presence of obesity in the absence of metabolic disturbances. The aim of our study was to analyse pro-inflammatory, nitro-oxidative stress, and insulin-resistance (IR) markers in metabolically healthy morbidly obese (MHMO) with respect to metabolically unhealthy morbidly obese (MUHMO) with metabolic syndrome (MS) and to identify the potential predictors of MS in the MHMO group. Two groups of MHMO and MUHMO with MS were analysed. We evaluated serum high sensitivity C reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), chemerin, nitrite and nitrate (NOx), total oxidant status (TOS), total antioxidant response (TAR), fasting blood glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR.) MHMO have similar hsCRP and TNF-α values as the MUHMO with MS, while chemerin was significantly lower in MHMO. NOx was higher in MUHMO with MS patients, while no difference regarding TOS and TAR was found between the two groups. HOMA-IR and insulin values were lower in MHMO as compared to the MUHMO with MS group. Insulin, HOMA-IR, and chemerin were identified predictors of MS in MHMO. In conclusion, MHMO and MUHMO display similarities and differences in terms of chronic inflammation, nitro-oxidative stress, and IR. Markers of IR and chemerin are possible predictors of MS in MHMO.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jinhua Liu ◽  
Ying Xie ◽  
Zhujun Han ◽  
Hailong Wang ◽  
Wenhu Xu

Abstract Introduction The aim of the study was to investigate the mitigative effects of bisoprolol (BIS) in cadmium-induced myocardial toxicity on oxidative stress and its inhibitive effect on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signalling in rats. Material and Methods Male albino Wistar rats were assigned to control, Cd, BIS 2 (2 mg/kg b.w.) and BIS 8 (8 mg/kg b.w.) groups with nine rats in each. Over four weeks, the control group was administered 1% gum acacia, all other groups received 3mg/kg b.w. CdCl2 dissolved in distilled water, and the BIS groups were additionally given bisoprolol in gum acacia. Blood samples were collected for biochemical estimations. Blood pressure and serum biomarker (lactate dehydrogenase, aspirate transaminase, alanine transferase and creatine kinase-MB, enzyme (superoxide dismutase, lipid hydroxy peroxidase, catalase and malondialdehyde), and tumour necrosis factor alpha (TNF-α) concentrations were measured. Western blot analysis was conducted for NF-κB and glutathione S-transferase (GST). After sacrificing the rats, cardiac tissue samples were examined histopathologically. Results Our findings pointed to a significant decrease (P < 0.05) in the studied serum biomarkers and levels of the relevant enzymes in the BIS 8 group compared to the Cd group. A significant decrease (P < 0.05) in NF-kB p65 expression and TNF-α levels was noted in the BIS 8 group relative to the BIS 2 and Cd groups, indicating a reduction at a higher dose. In microscopy, histopathological changes in the cardiac muscles of the BIS 8 group were evident compared to those of the Cd group. Conclusion BIS seemed to have protective effects against cardiac injury induced by cadmium and could be considered a novel therapeutic drug and prognostic biomarker in the pathology of the many cardiovascular diseases caused by heavy metal intake.


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