Xanthine Oxidase Levels Research Articles

Geraniol protects hippocampal CA1 neurons and improves functional outcomes in global model of stroke in rats.

Geraniol (GE), an acyclic monoterpene, is a chief constituent of essential oils of herbs and fruits. It possesses diverse pharmacological actions like antioxidant, anti-inflammatory, anti-apoptotic, and anti-parkinson. However, its neuroprotective potential in stroke is yet to be explored at large. The present study evaluated the neuroprotective potential of GE against the global model of cerebral ischemia/reperfusion (I/R)-injury in rats. Bilateral common carotid artery (BCCA) occlusion for 30 min followed by 7 days of reperfusion caused varied biochemical/enzymatic alterations viz. increase in levels of lipid peroxidation (LPO), nitric oxide (NO), xanthine oxidase (XO), and decrease in the levels of cerebroprotectives like superoxide dismutase (SOD), catalase (CAT), total thiols, and glutathione (GSH). GE-pretreatment markedly reversed these changes and restored the levels of protective enzymatic and non-enzymatic antioxidants near to normal compared to I/R group. Besides, GE treatment showed marked improvement in anxiety-related behavior and neuronal deficits in animals subjected to I/R injury. Moreover, 2,3,5-triphenyl tetrazolium chloride (TTC)-stained rat brain coronal sections and histopathological studies revealed neuronal protection against I/R-injury, as evidenced by a reduction in infarct area (%) and an increase in hippocampal CA1 neuronal density in the GE-treated groups. The results of this study revealed that GE exhibited potential neuroprotective activity by reducing oxidative stress and infarction area, and protecting hippocampal CA1 neurons against I/R-injury in the global stroke model in rats.

The Anti-hyperuricemia and Anti-inflammatory Effects of Atractylodes Macrocephala in Hyperuricemia and Gouty Arthritis Rat Models.

Atractylodes macrocephala is a traditional Chinese medicine with a variety of pharmacological activities. This study aimed to evaluate its anti-hyperuricemia and antiinflammatory effects on gout, and to preliminarily explore its mechanism. The hyperuricemia rat model was established by intraperitoneal injection of oteracil potassium and intragastric gavage of yeast powder solution. And the acute gouty arthritis (GA) model was established by injecting monosodium urate (MSU) suspension. In the study of the antihyperuricemia effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, hyperuricemia group allopurinol group as well as low, moderate and high dose groups of Atractylodes macrocephala decoction (N=8 rats in each group). Serum, liver and kidney tissue samples were collected from each group. Serum uric acid (UA), adenosine deaminase (ADA) and xanthine oxidase (XOD) levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Protein levels of ADA and XOD in liver tissues were detected by Western blot, and renal histological changes were observed by Hematoxylin-eosin (H&E) and Masson staining. In order to investigate the anti-inflammatory effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, GA group, colchicine group, high, moderate and low dose groups of Atractylodes macrocephala decoction (N=8 rats in each group), and serum and synovial tissue of each group were collected. Then the level of serum interleukin (IL)-1β and tumor necrosis factor (TNF)-α was observed by ELISA, and the histological changes of synovial tissue were observed by H&E staining. Besides, the expression of adenosine monophosphate- activated protein kinase (AMPK) /silent information regulator (SIRT) 1/ nuclear factor kappa B (NF-κB) protein in synovial tissue was observed by Western blot and immunohistochemistry. The markers of M1 and M2 macrophages, inducible nitric oxide synthase (iNOS) and arginase-1 (ARG1) were observed by Western blot and immunofluorescence. Atractylodes macrocephala could reduce the production of UA by inhibiting the level of ADA and XOD, and could improve renal injury and fibrosis. In addition, Atractylodes macrophages could reduce the levels of IL-1β and TNF-α, activate AMPK/SIRT1 signaling pathway, and inhibit the activation of NF-κB and the polarization of macrophages to a pro-inflammatory phenotype. Atractylodes macrocephala shows good anti-hyperuricemic and anti-inflammatory effects, and its anti-inflammation pharmacological activity may be related to the inhibition of M1 macrophage polarization and NF-κB activation through activating AMPK/SIRT1.

Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Release of hepatic xanthine oxidase (XO) to the circulation is protective in intravascular hemolytic crisis

Xanthine oxidase (XO) catalyzes the catabolism of hypoxanthine to xanthine and xanthine to uric acid, generating oxidants as a byproduct. Importantly, XO activity is elevated in numerous hemolytic conditions including sickle cell disease (SCD); however, the role of XO in this context has not been elucidated. Whereas long-standing dogma suggests elevated levels of XO in the vascular compartment contribute to vascular pathology via increased oxidant production, herein, we demonstrate, for the first time, that XO has an unexpected protective role during hemolysis. Using an established hemolysis model, we found that intravascular hemin challenge (40 μmol/kg) resulted in a significant increase in hemolysis and an immense (20-fold) elevation in plasma XO activity in Townes sickle cell phenotype (SS) sickle mice compared to controls. Repeating the hemin challenge model in hepatocyte-specific XO knockout mice transplanted with SS bone marrow confirmed the liver as the source of enhanced circulating XO as these mice demonstrated 100% lethality compared to 40% survival in controls. In addition, studies in murine hepatocytes (AML12) revealed hemin mediates upregulation and release of XO to the medium in a toll like receptor 4 (TLR4)-dependent manner. Furthermore, we demonstrate that XO degrades oxyhemoglobin and releases free hemin and iron in a hydrogen peroxide-dependent manner. Additional biochemical studies revealed purified XO binds free hemin to diminish the potential for deleterious hemin-related redox reactions as well as prevents platelet aggregation. In the aggregate, data herein reveals that intravascular hemin challenge induces XO release by hepatocytes through hemin-TLR4 signaling, resulting in an immense elevation of circulating XO. This increased XO activity in the vascular compartment mediates protection from intravascular hemin crisis by binding and potentially degrading hemin at the apical surface of the endothelium where XO is known to be bound and sequestered by endothelial glycosaminoglycans (GAGs).

The clinical value of serum xanthine oxidase levels in patients with acute ischemic stroke

Xanthine oxidase (XO), a form of xanthine oxidoreductase, is widely distributed in various human tissues. As a major source for the generation of superoxide radicals, XO is involved in the induction of oxidative stress and inflammation during ischemic and hypoxic tissue injury. Therefore, we designed this study to identify the role of serum XO levels in acute ischemic stroke (AIS) pathogenesis. In this single-center prospective study, 328 consecutive patients with AIS for the first time were included, and 107 age- and sex-matched healthy controls from a community-based stroke screening population were also included. The serum levels of XO and several conventional stroke risk factors were assessed. Multivariate analysis was applied to evaluate the relationship between serum levels of XO and clinical outcomes, and nomogram models were developed to predict the onset, progression and prognosis of AIS. Compared with the healthy control group, the serum level of XO was significantly higher in the AIS group (P < 0.05) and was an independent risk factor for AIS (OR 8.68, 95% CI 4.62–14.33, P < 0.05). Patients with progressive stroke or a poor prognosis had a much higher serum level of XO than patients with stable stroke or a good prognosis (all P < 0.05). In addition, the serum level of XO was an independent risk factor for stroke progression (OR 1.98, 95% CI 1.12–3.50, P = 0.018) and a poor prognosis (OR 2.51, 95% CI 1.47–3.31, P = 0.001). The nomogram models including XO to predict the onset, progression and prognosis of AIS had good prediction and differentiation abilities. The findings of this study show that the serum level of XO on admission was an independent risk factor for AIS and had certain clinical predictive value for stroke progression and prognosis in patients with AIS.

The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation.

The primary sources of reactive oxygen species (ROS) that cause ischemia-reperfusion (I/R) injuries are enzymes xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) in the literature, whereby one of the main ROS producing cells via NOX activity are polymophonuclear leukocytes (PNL). Sugammadex, the effect of which we plan to research against gastric I/R damage, is a modified gamma-cyclodextrin that antagonizes the action of steroidal neuromuscular blocking drugs. Previous studies have reported that sugammadex inhibits PNL infiltration. However, it is unknown whether an inhibitory effect on XO is present. We aimed to biochemically and histopathologically investigate the effects of sugammadex on I/R-induced stomach damage in rats. The animals were divided into groups that underwent gastric ischemia-reperfusion (GIR), 4 mg/kg sugammadex + gastric ischemia-reperfusion (SGIR), and a sham operation group (SG). The effect of sugammadex was evaluated by measuring oxidant-antioxidant and PNL parameters. There was no significant difference in XO levels between the SGIR and GIR groups. In the SGIR group, sugammadex inhibited the increase in myeloperoxidase (MPO) and malondialdehyde (MDA) levels (p < 0.001). The amount of MDA and MPO in the SGIR group was similar as in the SG group. Sugammadex significantly suppressed the decrease in tGSH levels in the SGIR group (p < 0.001). The difference between tGSH levels in the SG and SGIR groups was slight. In the SGIR group, sugammadex significantly suppressed the increase in tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL1-β) levels compared to the GIR group (p < 0.001). Additionally, sugammadex corrected histopathological modifications as much as sham group. In conclusion, sugammadex may be beneficial in preventing oxidative stress.

Efficacy of Green Extracting Solvents on Antioxidant, Xanthine Oxidase, and Plant Inhibitory Potentials of Solid-Based Residues (SBRs) of Cordyceps militaris

Solid-based residues (SBRs) of Cordyceps militaris are often considered as waste after the cultivation of the fruiting body. To demonstrate the value of this by-product, different ratios of two favorable green solvents (EtOH and water) were employed to optimize the yields of cordycepin (Cor) and adenosine (Ado) and investigate relevant activities of plant growth inhibition (allelopathy), antioxidants, and xanthine oxidase. The SBR extracts of 60% EtOH-40% water (W4) and 40% EtOH-60% water (W6) exhibited the highest antioxidant activity as well as yielded the optimum content of Cor and Ado. The W4 and Wt (hot water) exhibited maximum inhibitory effects on the growth of Raphanus sativus (radish), Lactuca sativa (lettuce) and two noxious weeds, Echinochloa crus-galli (barnyard grass) and Bidens pilosa (beggarticks). Furthermore, GC-MS scan analysis revealed the presence of 14 major compounds in the SBRs. W4 is the best solvent to optimize yields of Cor and Ado, as well as having the strongest levels of antioxidant activity, xanthine oxidase, and growth-inhibitory activity. This study reveals that SBRs are a potential source of medicinal and agricultural utilization.

Association of serum xanthine oxidase levels with hypertension: a study on Bangladeshi adults

Xanthine oxidase (XO) is a metalloflavoenzyme associated with the uric acid formation in purine metabolism. Serum XO has been suggested to be associated with liver and kidney dysfunction, diabetes and cardiovascular diseases. However, there is limited information on the relationship between serum XO levels and hypertension. This study aimed to assess the relationship between serum XO levels and hypertension in Bangladeshi adults. In this study, fasting blood samples were collected from 312 participants (225 males and 87 females), aged ≥ 20 years. Serum levels of XO were determined by ELISA and other biochemical parameters including serum uric acid (SUA) were measured by colorimetric methods. Hypertension was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg or self-reported recent use of anti-hypertensive medications. Association between serum XO levels and hypertension was evaluated by multinomial logistic regression analysis. The mean level of XO was significantly higher (p < 0.001) in females (5.8 ± 3.2 U/L) than in males (3.9 ± 2.5 U/L). When the participants were divided by blood pressure levels, the mean level of serum XO was significantly higher (p < 0.01) in the hypertensive group (5.0 ± 2.7 U/L) compared to the normotensive control group (4.0 ± 2.7 U/L). An increasing trend for SBP and DBP levels was observed across the XO quartiles (at least p < 0.01 for both cases). A significant positive correlation was found for XO with SBP and DBP (p < 0.01). In regression analysis, the serum levels of XO showed a significant and independent association with hypertension prevalence. In conclusion, the mean level of serum XO was significantly higher in hypertensive individuals and XO was independently associated with the prevalence of hypertension. Our results indicate that XO may have a potential role in the pathophysiology of elevated blood pressure through generating of reactive oxygen species. Further large-scale longitudinal studies are needed to determine the underlying mechanisms between XO and hypertension.

Co-exposure to aflatoxin B1 and therapeutic coartem worsens hepatic and renal function through enhanced oxido-inflammatory responses and apoptosis in rats

Aflatoxin B1 (AFB1) is a mycotoxin synthesised as a secondary metabolite by members of the Aspergillus species contaminating agricultural produce. Aspergillus species thrive in tropical climes, endemic to malaria. Artemisinin-based combination therapies (ACTs) effectively treat and prevent malaria recrudescence; Coartem (COA) is an ACT whose toxicity is evident. Although there are scanty studies on COA toxicity, the scientific literature is replete on AFB1 toxic effects -including carcinogenicity. The current research investigates AFB1 and COA toxicity in experimental Wistar rats' hepatorenal systems. Thirty albino rats were randomly grouped into five cohorts (n = 6) and treated as follows: Group I: Untreated control (2 mL/kg of corn oil); group II: AFB1 alone (70 μg/kg); group III: COA alone (5 mg/kg); group IV: COA and a low dose of AFB11 (5 mg/kg & 35 μg/kg); while Group V: COA and a high dose AFB12 (5 mg/kg & 70 μg/kg) by gavage. Our results show that exposure to AFB1 and COA significantly (p < 0.05) reduced superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase activities, besides reduced glutathione and total sulfhydryl groups level. Reactive oxygen and nitrogen species, lipid peroxidation, 8-hydroxy-2′-deoxyguanosine, nitric oxide, xanthine oxidase, and myeloperoxidase levels were increased (p < 0.05) in rats co-treated with COA and AFB1. Cell death was aggravated in COA and AFB1 groups, exemplified by increased Caspase-3 and 9 activities and alterations in the typical histological features of experimental rats’ livers and kidneys. Finally, rats co-treated with AFB1 and COA experienced increased hepatorenal dysregulation, oxidative and inflammatory tissue damage, and apoptotic cell death. All the observed systemic perturbations occurred dose-dependently. It is crucial, therefore, to prevent AFB1 dietary contaminations during COA therapeutic regimen due to increased pathophysiological damage exerted on experimental rat liver and kidneys, as evidenced in this study.

Assessment of the relationship between serum xanthine oxidase levels and type 2 diabetes: a cross-sectional study

Xanthine oxidase (XO) is an enzyme associated with purine metabolism. The relationship between XO levels and type 2 diabetes (T2D) is not clear yet or little is known so far. Therefore, we conducted a cross-sectional study to determine the association of XO levels with T2D in a Bangladeshi adult cohort. A total of 325 participants (234 males and 91 females) were enrolled in the study. The participants were divided into three groups; diabetic (n = 173), prediabetic (n = 35), and non-diabetic control (n = 117). Serum levels of XO were measured by enzyme-linked immunosorbent assay (ELISA) and other biochemical parameters including fasting blood glucose (FBG), serum uric acid (SUA), and lipid profile markers measured by colorimetric methods. Participants with T2D were confirmed according to the definition of the American Diabetic Association. The association between serum XO levels and T2D was determined by logistic regression models. The mean level of serum XO was significantly higher in females (6.0 ± 3.7 U/L) compared to male (4.0 ± 2.8 U/L) participants (p < 0.001). In contrast, males had a higher mean level of SUA (6.1 ± 1.9 mg/dL) than female (4.4 ± 1.9 mg/dL) participants (p < 0.001). The mean level of XO was significantly higher in the diabetic group (5.8 ± 3.6 U/L) compared to the prediabetic (3.7 ± 1.9 U/L) and control (2.9 ± 1.8 U/L) groups (p < 0.001). On the other hand, the mean SUA concentration was significantly lower in the diabetic group than in the other two groups (p < 0.001). A significant increasing trend was observed for FBG levels across the XO quartiles (p < 0.001). A decreasing trend was found for SUA levels in the XO quartiles (p < 0.001). Serum levels of XO and SUA showed a positive and negative correlation with FBG, respectively. In regression analysis, serum XO levels showed an independent association with T2D. In conclusion, this study reports a positive and independent association between XO levels and T2D in Bangladeshi adults. Monitoring serum levels of XO may be useful in reducing the risk of T2D. Further research is needed to determine the underlying mechanisms of the association between elevated XO levels and T2D.

Anti-Gouty Arthritis and Anti-Hyperuricemia Properties of Sanghuangporus vaninii and Inonotus hispidus in Rodent Models.

Acute inflammation and hyperuricemia are associated with gouty arthritis. As an edible and therapeutic mushroom, Sanghuangporus vaninii (SV) has an inhibitory effect on tumorigenesis, and Inonotus hispidus (IH) exhibits anti-tumor, anti-inflammatory, and antioxidant properties. In this study, uric acid (UA) and xanthine oxidase (XOD) levels in hyperuricemic mice were examined to determine the regulatory effects of SV and IH. SV and IH reversed the pathogenic state of elevated UA levels in the serum and reduced levels of XOD in the serum and liver of mice with hyperuricemia. SV and IH affected the inflammatory response in rats with acute gouty arthritis. Compared to vehicle-treated rats, monosodium urate crystals (MSU) increased the swelling ratio of the right ankle joints. SV and IH administration significantly reduced swelling and inflammatory cell infiltration. SV reduced the levels of interleukin-8 (IL-8) and chemokine ligand-2 (CCL-2), whereas IH reduced the levels of matrix metalloproteinase-9 (MMP-9), CCL-2, and tumor necrosis factor-α (TNF-α), which were confirmed in articular soft tissues by immunohistochemistry. In summary, our data provide experimental evidence for the applicability of SV and IH in gouty arthritis and hyperuricemia treatment.

Anti-inflammatory effects of oral and intraperitoneal administration of cerium oxide nanoparticles on experimental hepatic ischemia-reperfusion injury.

Hepatic ischemia-reperfusion (IR) injury occurs in liver surgery, resection, and transplantation. Reactive oxygen species (ROS) produced following IR starts the cascade of cell damage, necrosis/apoptosis, and proinflammatory responses by activating intracellular signaling cascade to drive hepatocellular damage. Cerium oxide nanoparticles (CONPs) act as anti-inflammatory and antioxidant agents. Thus, we evaluated the protective effects of oral (o.g.) and intraperitoneal (i.p.) administration of CONPs on hepatic IR injury. Mice were randomly divided into five groups: control, sham, IR protocol, CONP+IR (i.p.), and CONP+IR (o.g.). Mouse hepatic IR protocol was applied to the animals in the IR group. CONPs (300 μg/kg) were administered 24 hours before IR protocol. Blood and tissue samples were taken after the reperfusion period. Hepatic IR injury markedly increased enzyme activities, tissue lipid peroxidation, myeloperoxidase (MPO), xanthine oxidase (XO), nitrite oxide (NO), and tissue nuclear factor kappa-B (NF-κB) p65 levels, plasma pro-inflammatory cytokines, chemokines, and adhesion molecules while decreasing antioxidant markers and caused pathological changes in hepatic tissue. The expression of tumor necrosis factor alpha (TNF-α), matrix metalloproteinase 2 (MMP-2), and 9 increased, and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) expression decreased in the IR group. Pretreatment with CONPs o.g. and i.p. 24 hours before hepatic ischemia improved the biochemical parameters above and alleviated the histopathological findings. Results of the present study demonstrate a significant reduction in liver degeneration by administering CONPs via i.p. and o.g. route in an experimental liver IR model, suggesting that CONPs have the extensive potential to prevent hepatic IR injury.

Discovery of derivatives from Spartina alterniflora-sourced moiety as xanthine oxidase inhibitors to lower uric acid

In this work, hit compounds Spartinin F1-F20 sharing the Spartina alterniflora-sourced ferulic acid backbone were synthesized and evaluated on inhibiting xanthine oxidase and lowering uric acid level. The top hit Spartinin F2 exhibited inhibition percentages at 10 μM dosage as high as 84.48 (higher than that of the positive control allopurinol) and low cyto-toxicity. Spartinin F2 inferred potential efficiency in lowering the serum UA level (from 631.6 μM to 295.0 μM), which was comparable with allopurinol (to 309.2 μM). Spartinin F2 was also beneficial for other serum indexes. The bioavailability of Spartinin F2 was 63.71% from the preliminary pharmacokinetics test and the molecular docking simulation indicated that except for retaining the hydrogen bonds with the key residues such as THR 1010 and LYS 771, the introduction of the π-sulfur interactions via the sulfonate might also be beneficial for developing more potent XO inhibitors.

Naringenin Prevents Inflammation, Apoptosis, and DNA Damage in Potassium Oxonate-Induced Hyperuricemia in Rat Liver Tissue: Roles of Cytochrome C, NF-κB, Caspase-3, and 8-Hydroxydeoxyguanosine.

Background: Hyperuricemia (HU) is a metabolic disease characterized by high uric acid levels in the blood. HU is a risk factor for diabetes, cardiovascular complications, metabolic syndrome, and chronic kidney disease. Purpose: The present study was performed to determine the effect of experimental HU on xanthine oxidase (XO), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), interleukin-17 (IL-17), cytochrome C, glutathione peroxidase (GPx), caspase-3, and 8-hydroxydeoxyguanosine (8-OHdG) levels in liver tissues of rats. Study Design: Thirty-five, male, Wistar albino-type rats were used for this study. Experimental groups were formed as follows: Group 1: control group; Group 2: potassium oxonate (PO) group; group 3: PO+NAR (naringenin; 2 weeks) group; and Group 4: PO (2 weeks)+NAR (2 weeks) group (total of 4 weeks). Methods: The first group was not given anything other than normal rat food and drinking water. In the second group, a 250 mg/kg intraperitoneal dose of PO was administered for 2 weeks. In the third group, 250 mg/kg intraperitoneal PO (application for 2 weeks) and 100 mg/kg NAR intraperitoneally 1 hr after each application were administered. In the fourth group, intraperitoneal PO administration was applied for 2 weeks, followed by intraperitoneal administration of NAR for 2 weeks (4 weeks in total). At the end of the experimental period, XO, TNF-α, NF-κB, IL-17, cytochrome C, GPx, caspase-3, and 8-OHdG levels were determined in liver tissues. Results: HU increased XO, TNF-α, NF-κB, IL-17, cytochrome C, caspase-3, and 8-OHdG levels in liver tissues. However, both 2 and 4 weeks of NAR supplementation decreased these values, and also NAR supplementation led to an increase in GPx levels in tissues. Conclusions: The results of the study show that increased inflammation, apoptosis, and DNA damage in experimental HU can be prevented by administration of NAR due to inhibition of cytochrome C, NF-κB, caspase-3, and 8-OHdG.

Study of purine derivatives and their relation to renal disorders in patients with psoriasis.

Psoriasis (Pso) is a chronic proliferative skin condition associated with hyperuricemia that may impair renal function. The current study investigates the correlation between purine derivatives (PDs) and renal function in patients with Pso. This case-control study comprises 30 psoriatic patients and 30 age- and sex-matched healthy controls. The enzyme-linked immunosorbent assay (ELISA) was used to assess serum xanthine oxidase (XO) and urine albumin levels. Serum uric acid (SUA) and urinary creatinine were measured using the colorimetric method. There was a rise in the related PDs levels in patients with Pso compared to controls, as evidenced by the enhanced SUA levels (p < 0.001) and XO levels (p < 0.001). The presence of the related PDs in the serum was linked to the severity of Pso, and there was also a connection between the related PDs levels in the blood and indicators of renal dysfunction. Moreover, SUA and urinary albumin creatinine ratio (UACR) were found to be significantly correlated (r = 0.371 and p = 0.044), as were XO and UACR (r = 0.422 and p = 0.020). In psoriatic patients with itching and palmoplantar affection, mean SUA levels were considerably more significant than those in other instances (p = 0.005 and p = 0.018, respectively). Pso, being a hyperproliferative disease, is associated with hyperuricemia, which has a harmful effect on kidney function. The related PDs may be unique serological biomarkers for patients with Pso who are at high risk of developing renal abnormalities, especially with higher severity scores.

Effects of 2-Year Nutritional and Lifestyle Intervention on Oxidative and Inflammatory Statuses in Individuals of 55 Years of Age and over at High Cardiovascular Risk.

Obesity and overweight are disorders with high impact on the morbidity and mortality of chronic diseases, such as type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). We aim to assess the effects of 2-year nutritional and lifestyle intervention on oxidative and inflammatory status in individuals of 55 years of age and over at high CVD risk. Participants (n = 100 individuals of 55 years of age and over living in the Balearic Islands, Spain) were randomized into control and intervention group. Anthropometric and haematological parameters, blood pressure and physical activity were measured before and after the intervention. Oxidative and inflammatory biomarkers in plasma, urine, peripheral blood mononuclear cells (PBMCs) and neutrophils were determined. A higher reduction in abdominal obesity, blood pressure and triglycerides levels was observed after a 2-year intervention. An improvement of oxidative stress and proinflammatory status was demonstrated with a significant reduction in myeloperoxidase, xanthine oxidase, malondialdehyde and monocyte chemoattractant protein-1 (MCP1) levels, and an increase in polyphenols in plasma was observed. A decrease in reactive oxygen species production in PBMCs and neutrophils levels after zymosan and lipopolysaccharide activation was found in the intervention group with respect to the control group. The intervention with hypocaloric Mediterranean Diet and customized physical activity improves oxidative stress and proinflammatory status and could contribute to decreasing the CVD risk.

Dexamethasone Promotes the Risk of Cardiovascular Disease in High Fructose-exposed Wistar Rats

Background: Dyslipidemia constitutes a serious public health concern globally. It has been established that excessive fructose intake results in dyslipidemia; however, whether dexamethasone aggravates or alleviates fructose-induced dyslipidemia is unknown. Thus, we examined the effects of dexamethasone on dyslipidemia and hyperuricemia in high fructose-taking Wister rats. Materials and Methods: Twenty male Wister rats were randomly grouped as control (distilled water), fructose (10% fructose w/v), dexamethasone (0.2 mg/kg, PO) and fructose+dexamethasone. After a 21-day exposure, the serum and heart samples were harvested, processed and analyzed for biochemical assays. Results: Our findings reveal that exposure of rats to high fructose significantly increased blood glucose, elevated serum triglycerides and uric acid, activity of xanthine oxidase, and lowered high density lipoprotein cholesterol (HDL) level. However, dexamethasone administration had no significant effect on the blood glucose and did not alter the serum levels of triglycerides, uric acid and xanthine oxidase. Meanwhile, both fructose and dexamethasone treatments independently elevated the serum levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL) and malondialdehyde. Further, the fructose treatment elevated the TG/HDL ratio, while both fructose and dexamethasone treatments individually and synergistically elevated TC/HDL ratio. Our study also showed that co-administration of fructose and dexamethasone aggravated the elevated serum levels of TC and LDL, while it impaired the enzymatic antioxidant systems. Conclusion: Dexamethasone, though slightly reduced fructose-induced hyperglycemia, impaired the antioxidant enzymes and escalated dyslipidemia during fructose intake. Hence, our study suggests that dexamethasone administration may increase the risk of CVD in animals with excessive intake of fructose.

Network pharmacology and in vivo experiments reveal the pharmacological effects and molecular mechanisms of Simiao Powder in prevention and treatment for gout

BackgroundGout is a common disease with high incidence due to unhealthy diet and living habits. Simiao Powder, as a classic formula consisted of four common herbs, has been widely used in clinical practice since ancient times to prevent and treat gout. However, the pharmacological mechanism of Simiao Powder is still unclear.MethodsBased on network pharmacology, Simiao Powder active compounds were identified in TCMSP, ETCM and BATMAN database, used to establish a network of interaction between potential targets of Simiao Powder and known therapeutic targets of gout. Subsequently, the key potential targets are being used for protein–protein interaction, GO enrichment analysis and KEGG pathway enrichment analysis through several authoritative open databases. Molecular docking through AutoDockTools software can verify interaction between molecules. Finally, to validate the predicted results, in vivo experiments based on hyperuricemic-gout mice model were designed and treated with Simiao powder and allopurinol. Serum levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN) and xanthine oxidase (XOD) were determined using a customized assay kit while the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA were analyzed through qRT-PCR.ResultsDisease-target-compound network was visualized basing on the 20 bioactive compounds and the 19 potential targets using Cytoscape software. The results of PPI analysis, GO enrichment and KEGG pathway enrichment analysis indicate that the potential mechanism of Simiao Powder in treating gout may be achieved by regulating immune and inflammatory reactions, improving metabolism and endocrine. The results of molecular docking show that most of the targets and components have good binding activity. In vivo experiments revealed that Simiao powder can decreased serum UA and XOD levels in hyperuricemic-gout mice, and improved renal function. Furthermore, Simiao powder certainly regulates the expression of PPAR-γ, PTGS1, IL-6 and Bcl2 mRNA in ankle tissue in hyperuricemic-gout mice.ConclusionCollectively, this research predicted a multiple compounds, targets, and pathways model mechanism of Simiao Powder in the prevention and treatment of gout, providing new ideas and methods for in-depth research, via vivo experiments.

​Clinical Study on Penicillin Anaphylaxis and Role of Oxidative Stress and Pro-inflammatory Markers: An Implication for Therapy

Background: Penicillin belongs to the β-Lactam group of antibiotics which is used as a first-line drug in veterinary medicine. The occurrence of penicillin anaphylaxis and its pathophysiology is rarely reported in ruminants. Methods: In the present study, oxidative stress and pro-inflammatory response were investigated in 4 cases (Jersey crossbred) of penicillin hypersensitivity by assessing oxidative stress biomarkers and pro-inflammatory cytokines. Animals in the current experimental plan were divided into three groups, group I included penicillin hypersensitive (n=4), group II included penicillin tolerant (n=6) and group III (n=10), included healthy control animals. Result: Mean values of temperature, heart rate and respiration were significantly (p less than 0.05) elevated in the penicillin-sensitive group compared to the penicillin tolerant and control group. The present study revealed significantly (p less than 0.05) elevated levels of lipid peroxidation (MDA), xanthine oxidase (XO), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while as levels of glucose-6-phosphate dehydrogenase (G6PD), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were significantly reduced in the penicillin-sensitive group. Levels of G6PD showed significant positive correlation with GPx (r=0.54, P less than 0.001) and catalase (r=0.34, P less than 0.05) while as significant negative correlation with XO (r=0.39, P less than 0.05) was observed. Collectively, these findings indicate that the pathophysiology of penicillin hypersensitivity involves anti-oxidant imbalance and enhanced pro-inflammatory response and targeting these pathways can have therapeutic implications for penicillin hypersensitivity.

Effects of salinity stress on antioxidant status and inflammatory responses in females of a "Near Threatened" economically important fish species Notopterus chitala: a mechanistic approach.

In the present study, acute stress responses of adult female Notopterus chitala were scrutinized by antioxidant status and inflammation reaction in the gill and liver at five different salinity exposures (0, 3, 6, 9, 12 ppt). Oxidative defense was assessed by determining superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase, and glutathione reductase activities, while malondialdehyde (MDA), glutathione, and xanthine oxidase levels were determined as indicators of oxidative load. Pro-inflammatory cytokines (IL-1β, IL-6, IL-10, and TNFα) and caspase 1 levels were also analyzed. Expression levels of transcription factors (NRF2 and NF-κB) and molecular chaperons (HSF, HSP70, and HSP90) were estimated to evaluate their relative contribution to overcome salinity stress. MDA showed a significant (P < 0.05) increase (gill, + 25.35-90.14%; liver, + 23.88-80.59%) with salinity; SOD (+ 13.72-45.09%) and CAT (+ 12.73-33.96%) exhibited a sharp increase until 9 ppt, followed by a decrease at the highest salinity (12 ppt) (gill, - 3.92%; liver, - 2.18%). Levels of cytokines were observed to increase (+ 52.8-127.42%) in a parallel pattern with increased salinity. HSP70 and HSP90 expressions were higher in gill tissues than those in liver tissues. NRF2 played pivotal role in reducing salinity-induced oxidative load in both the liver and gills. Serum cortisol and carbonic anhydrase were measured and noted to be significantly (P < 0.05) upregulated in salinity stressed groups. Gill Na+-K+-ATPase activity decreased significantly (P < 0.05) in fish exposed to 6, 9, and 12 ppt compared to control. Present study suggests that a hyperosmotic environment induces acute oxidative stress and inflammation, which in turn causes cellular death and impairs tissue functions in freshwater fish species such as Notopterus chitala.