scholarly journals Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis

Author(s):  
Arwa Fadıl Haqi BALLUR ◽  
Eyup ALTINOZ ◽  
Gurkan YİGİTTURK ◽  
Melike Ozgul Onal ◽  
Hulya ELBE ◽  
...  

Abstract Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and anti-oxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (On the 30th day, single dose 20 mg/ml, intraperitoneal), MSU+MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU+PINX and MSU+PINX+MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU+MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1175
Author(s):  
Johanna Helmstädter ◽  
Karin Keppeler ◽  
Franziska Aust ◽  
Leonie Küster ◽  
Katie Frenis ◽  
...  

Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d; 3 days) and sepsis induced by CLP after one day of GLP-1 analog treatment. Survival and body temperature were monitored. Aortic vascular function (isometric tension recording), protein expression (immunohistochemistry and dot blot) and gene expression (qRT-PCR) were determined. Endothelium-dependent relaxation in the aorta was impaired by CLP and correlated with markers of inflammation (e.g., interleukin 6 and inducible nitric oxide synthase) and oxidative stress (e.g., 3-nitrotyrosine) was higher in septic mice, all of which was almost completely normalized by Lira therapy. We demonstrate that the GLP-1 analog Lira ameliorates sepsis-induced endothelial dysfunction by the reduction of vascular inflammation and oxidative stress. Accordingly, the findings suggest that the antioxidant and anti-inflammatory effects of GLP-1 analogs may be a valuable tool to protect the cardiovascular system from dysbalanced inflammation in polymicrobial sepsis.


2020 ◽  
Vol 245 (14) ◽  
pp. 1260-1267
Author(s):  
Sylwia Dzięgielewska-Gęsiak ◽  
Dorota Stołtny ◽  
Alicja Brożek ◽  
Małgorzata Muc-Wierzgoń ◽  
Ewa Wysocka

Insulin resistance (IR) may be associated with oxidative stress and leads to cardiovascular disorders. Current research focuses on interplay between insulin-resistance indices and oxidant-antioxidant markers in elderly individuals with or without insulin-resistance. The assessment involved anthropometric data (weight, height, BMI, percentage of body fat (FAT)) and biochemical tests (glucose, lipids, serum insulin and plasma oxidant-antioxidant markers: Thiobarbituric Acid-Reacting Substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1) and total antioxidant status). Insulin resistance index (IR) assuming a cut-off point of 0.3 allows to divides groups into: insulin sensitive group (InsS) IR < 0,3 ( n = 35, median age 69.0 years) and insulin-resistant group (InsR) IR ≥ 0.3 ( n = 51, median age 71.0 years). Lipids and antioxidant defense system markers did not differentiate the investigated groups. In the InsR elderly group, the FAT was increased ( P < 0.000003) and TBARS ( P = 0.008) concentration decreased in comparison with InsS group. A positive correlation for SOD-1 and total antioxidant status ( P < 0.05; r =  0.434) and a negative correlation for TBARS and age ( P < 0.05 with r = −0.421) were calculated in InsR individuals. In elderly individuals, oxidative stress persists irrespective of insulin-resistance status. We suggest that increased oxidative stress may be consequence of old age. An insulin action identifies those at high risk for atherosclerosis, via congruent associations with oxidative stress and extra- and intra-cellular antioxidant defense systems. Thus, we maintain that insulin-resistance is not the cause of aging. Impact statement Insulin resistance is associated with oxidative stress leading to cardiovascular diseases. However, little research has been performed examining elderly individuals with or without insulin-resistance. We demonstrate that antioxidant defense systems alone is not able to abrogate insulin action in elderly individuals at high risk for atherosclerosis, whereas the combined oxidant-antioxidant markers (thiobarbituric acid-reacting substances (TBARS), Cu,Zn-superoxide dismutase (SOD-1), and total antioxidant status (TAS)) might be more efficient and perhaps produce better clinical outcome. In fact, a decrease in oxidative stress and strong interaction between antioxidant defense can be seen only among insulin-resistant elderly individuals. This is, in our opinion, valuable information for clinicians, since insulin-resistance is considered strong cardiovascular risk factor.


2019 ◽  
Vol 14 (5) ◽  
pp. 595-607 ◽  
Author(s):  
Julius Z H von Martels ◽  
Arno R Bourgonje ◽  
Marjolein A Y Klaassen ◽  
Hassan A A Alkhalifah ◽  
Mehdi Sadaghian Sadabad ◽  
...  

Abstract Background and Aims Crohn’s disease [CD] is characterised by chronic intestinal inflammation and dysbiosis in the gut. Riboflavin [vitamin B2] has anti-inflammatory, antioxidant and microbiome-modulatory properties. Here, we analysed the effect of riboflavin on oxidative stress, markers of inflammation, clinical symptoms, and faecal microbiome in patients with CD. Methods In this prospective clinical intervention study, patients received 100 mg riboflavin [DSM, Nutritional Products Ltd] daily for 3 weeks. Clinical disease activity [Harvey-Bradshaw Index: HBI], serum biomarkers of inflammation and redox status [plasma free thiols], and faecal microbiome taxonomical composition and functionality [fluorescent in situ hybridisation: FISH; and metagenomic shotgun sequencing: MGS], were analysed before and after riboflavin intervention. Results In total, 70 patients with CD with varying disease activity were included. Riboflavin supplementation significantly decreased serum levels of inflammatory markers. In patients with low faecal calprotectin [FC] levels, IL-2 decreased, and in patients with high FC levels, C-reactive protein [CRP] was reduced and free thiols significantly increased after supplementation. Moreover, HBI was significantly decreased by riboflavin supplementation. Riboflavin supplementation led to decreased Enterobacteriaceae in patients with low FC levels as determined by FISH; however, MGS analysis showed no effects on diversity, taxonomy, or metabolic pathways of the faecal microbiome. Conclusions Three weeks of riboflavin supplementation resulted in a reduction in systemic oxidative stress, mixed anti-inflammatory effects, and a reduction in clinical symptoms [HBI]. FISH analysis showed decreased Enterobacteriaceae in patients with CD with low FC levels, though this was not observed in MGS analysis. Our data demonstrate that riboflavin supplementation has a number of anti-inflammatory and anti-oxidant effects in CD.


Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 146 ◽  
Author(s):  
Juana Rosado-Pérez ◽  
Itzen Aguiñiga-Sánchez ◽  
Edelmiro Santiago-Osorio ◽  
Víctor Manuel Mendoza-Núñez

Metabolic syndrome (MetS) is a risk factor for cognitive deterioration and frailty in older adults. In this regard it has been shown that oxidative stress (OxS) and chronic inflammation are involved in the pathophysiology of these alterations. Harmless antioxidant and anti-inflammatory therapeutic alternatives have been proposed, such as the consumption of Sechium edule (chayote), but the evidence is inconclusive. For this reason, an exploratory study of a single group chosen by convenience sampling, including 12 older adults, with an average age of 71 ± 6 years (10 women and 2 men) with a diagnosis of MetS according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) criteria. This exploratory study aimed to determine the effect of the consumption of the dried fruit powder supplement of Sechium edule var. nigrum spinosum (500 mg, 3 times per day) for six weeks on the markers of OxS in elderly adults with MetS. All participants’ OxS markers were measured before and after treatment. There was a statistically significant decrease in the concentration of lipoperoxides (baseline, 0.289 ± 0.04 vs. post-treatment, 0.234 ± 0.06 μmol/L, p < 0.05), together with a significant increase in total antioxidant status (baseline, 0.97 ± 0.18 vs. post-treatment, 1.2 ± 0.12 mmol/L, p < 0.05). In this sense, the oxidative stress index showed a statistically significant decrease (baseline, 1.7 ± 0.78 vs. post-treatment, 0.75 ± 0.87, p < 0.05). A statistically significant decrease in the concentration of TNF-α after treatment was also found (baseline, 5.3 ± 1.4 vs. post-treatment, 3.5 ± 1.3, p < 0.05).Our findings suggest that the consumption of the dry fruit of Sechium edule has an antioxidant and anti-inflammatory effect in older adults with metabolic syndrome.


Author(s):  
Hyun-Seung Rhyu ◽  
Kyung-Shin Park

This study investigated whether 10 month telephone follow-up intervention effectively stabilizes reductions in %body fat, and markers of inflammation and oxidative stress obtained from summer camp in obese Hispanic children. Fifty-six obese children (19 SUTI: summer camp and 10 months of follow-up telephone intervention, 18 SU: summer camp intervention only, and 19 CON: no intervention) completed this study. Anthropometric data and blood samples were obtained before (PRE), after 8 weeks of summer camp, and a 10month follow-up telephone intervention to measure markers of inflammation and oxidative stress. Eight weeks of summer camp significantly reduced %body fat, and levels of tumor necrosis factor-alpha, C-reactive protein and 8-hydroxydeoxyguanosine. It also elevated levels of adiponectin and total antioxidant status in SUTI and SU (p < 0.05). However, results of the 10month follow-up measurement were reverted back to PRE in SU, whereas the results for SUTI remained different to PRE (p < 0.05). Results confirm that levels of inflammation and oxidative stress are correlated to changes in %body fat, indicating that fat loss is effective in preventing and managing obesity-associated disorders. It is suggested that a telephone intervention is an effective follow-up tool for stabilizing reductions in %body fat as well as levels of inflammation and oxidative stress that were obtained from an intensive summer camp program in obese Hispanic children.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Nelli Giribabu ◽  
Nelli Srinivasarao ◽  
Somesula Swapna Rekha ◽  
Sekaran Muniandy ◽  
Naguib Salleh

Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized thatCentella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role ofC. asiaticaon the hippocampus in diabetes.Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200 mg/kg/day body weight (b.w)C. asiaticaleaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-α; interleukin, IL-6; and interleukin, IL-1β) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes.Results. Administration ofC. asiaticaleaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus ofC. asiaticaleaf aqueous extract treated diabetic rats.Conclusions.C. asiaticaleaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Eva-Maria Schweikert ◽  
Julianna Amort ◽  
Petra Wilgenbus ◽  
Ulrich Förstermann ◽  
John F. Teiber ◽  
...  

The pathogenPseudomonas aeruginosacauses serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl)-L-homoserine lactone (3OC12) and the redox-active pyocyanin (PCN). Paraoxonase-2 (PON2) may protect againstP. aeruginosainfections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca2+-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism againstP. aeruginosainfections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca2+-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate defense system againstP. aeruginosainfections. Furthermore, we conclude thatP. aeruginosacircumvents PON3 protection by the same pathway as for PON2. This may help identifying underlying mechanisms in order to sustain the protection afforded by these enzymes.


Author(s):  
Mamdooh Ghoneum ◽  
Mohamed S. A. El-Gerbed

Abstract Purpose Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. Methods Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed. Results MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture. Conclusion HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.


Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 285 ◽  
Author(s):  
Anket Sharma ◽  
Babar Shahzad ◽  
Vinod Kumar ◽  
Sukhmeen Kaur Kohli ◽  
Gagan Preet Singh Sidhu ◽  
...  

Plants face a variety of abiotic stresses, which generate reactive oxygen species (ROS), and ultimately obstruct normal growth and development of plants. To prevent cellular damage caused by oxidative stress, plants accumulate certain compatible solutes known as osmolytes to safeguard the cellular machinery. The most common osmolytes that play crucial role in osmoregulation are proline, glycine-betaine, polyamines, and sugars. These compounds stabilize the osmotic differences between surroundings of cell and the cytosol. Besides, they also protect the plant cells from oxidative stress by inhibiting the production of harmful ROS like hydroxyl ions, superoxide ions, hydrogen peroxide, and other free radicals. The accumulation of osmolytes is further modulated by phytohormones like abscisic acid, brassinosteroids, cytokinins, ethylene, jasmonates, and salicylic acid. It is thus important to understand the mechanisms regulating the phytohormone-mediated accumulation of osmolytes in plants during abiotic stresses. In this review, we have discussed the underlying mechanisms of phytohormone-regulated osmolyte accumulation along with their various functions in plants under stress conditions.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Víctor Manuel Mendoza-Núñez ◽  
Beatriz Isabel García-Martínez ◽  
Juana Rosado-Pérez ◽  
Edelmiro Santiago-Osorio ◽  
José Pedraza-Chaverri ◽  
...  

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of64±1years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline8.9±0.2vs. posttreatment8.6±0.3) and the PG (baseline8.8±0.2vs. posttreatment8.4±0.3) compared to the CG (baseline8.8±0.3vs. six months9.1±0.3) although the difference was not statistically significant (p<0.05). There was a statistically significant decrease (p<0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline100±3vs. posttreatment57±3, PG: baseline106±7vs. posttreatment77±5, and CG: baseline94±10vs. six months107±11pg/mL). Likewise, a statistically significant decrease (p<0.05) in the concentration of the RAGE was found in the EG (baseline1636±88vs. posttreatment1144±68) and the PG (baseline1506±97vs. posttreatment1016±82) compared to CG (baseline1407±112vs. six months1506±128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration numberISRCTN13159380.


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