Polyphenolic‑rich fraction of Pithecellobium dulce attenuates methotrexate‑induced oxidative stress and associated tissue injury by regulating the TNF‑α, IL‑1β and IL‑6 pro‑inflammatory cytokines

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

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The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up

Frontiers in Medicine ◽

10.3389/fmed.2021.714205 ◽

2021 ◽

Vol 8 ◽

Author(s):

Elodia Nataly Díaz-De la Cruz ◽

José Ignacio Cerrillos-Gutiérrez ◽

Andrés García-Sánchez ◽

Carlos Gerardo Prado-Nevárez ◽

Jorge Andrade-Sierra ◽

...

Keyword(s):

Oxidative Stress ◽

Calcium Carbonate ◽

Inflammatory Cytokines ◽

C Reactive Protein ◽

Reactive Protein ◽

Sevelamer Hydrochloride ◽

Tnf Α ◽

Compensatory Effect ◽

Pro Inflammatory Cytokines

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

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Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord

International Journal of Molecular Sciences ◽

10.3390/ijms21197425 ◽

2020 ◽

Vol 21 (19) ◽

pp. 7425

Author(s):

Hyo Young Jung ◽

Hyun Jung Kwon ◽

Woosuk Kim ◽

Kyu Ri Hahn ◽

Seung Myung Moon ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Inflammatory Cytokines ◽

Neuronal Death ◽

Microglial Activation ◽

Ventral Horn ◽

Phosphoglycerate Mutase ◽

Ischemic Damage ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α.

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Beneficial effects of combined therapy with lacidipine and candesartan in obese hypertensive patients

Romanian Journal of Internal Medicine ◽

10.2478/rjim-2018-0018 ◽

2018 ◽

Vol 56 (4) ◽

pp. 257-264

Author(s):

Tatiana Ashcheulova ◽

Nina Gerasimchuk ◽

Olga Kovalyova ◽

Oleksii Honchar

Keyword(s):

Oxidative Stress ◽

Endothelial Function ◽

Antihypertensive Therapy ◽

Inflammatory Cytokines ◽

Overweight And Obesity ◽

Oxidative Stress Marker ◽

Hypertensive Patients ◽

Tnf Α ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

Abstract Introduction. Obesity is becoming one of the leading risk factors of coronary heart disease, hypertension, cerebrovascular disease. Despite the presence of a large number of antihypertensive agents and scientific substantiation of antihypertensive treatment principles it would be wrong to assume that the problem is completely solved. Development of endothelial dysfunction is one of the key pathogenic mechanisms in hypertension. This process is proven to have contributed by immune inflammation activation which is mediated by pro-inflammatory cytokines and oxidative stress. Aims. To investigate the additional benefits of the combined antihypertensive therapy with lacidipine and candesartan on the basis of studying their antioxidant properties, impact on endothelial function and pro-inflammatory cytokines activity in hypertensive patients with overweight and obesity. Methods. A combination of a calcium channel blocker and angiotensin receptor blocker (lacidipine 2 mg, 4 mg, and candesartan 4mg, 8mg, 16mg) was prescribed to 30 patients with essential hypertension of grades 1-3, 30 to 65 years old (mean age - 54.7 ± 5.8 years), who previously have not been receiving regular antihypertensive therapy. Results. During the course of combined antihypertensive therapy with lacidipine and candesartan, a significant reduction in i-NOS activity, TNF-α to its type I soluble receptor ratio (TNF- α/sTNF-αRI), and oxidative stress marker - 8-iso-PgF2α has been observed. Activity of e-NOS, levels of SOD and catalase, in contrast, have increased by the end of observation period. Conclusion. The improvement of endothelial function due to lower level of oxidative stress and a significant decrease of immune activation has been observed in hypertensive patients with overweight and obesity under the influence of combined antihypertensive therapy with lacidipine and candesartan.

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Acute inflammation and oxidative stress induced by lipopolysaccharide and the ameliorative effect of stingless bee honey

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200918152111 ◽

2020 ◽

Vol 23 ◽

Author(s):

Yazan Ranneh ◽

Ayman M. Mahmoud ◽

Abdulmannan Fadel ◽

Mohammed Albujja ◽

Abdah Md Akim ◽

...

Keyword(s):

Oxidative Stress ◽

P38 Mapk ◽

Inflammatory Cytokines ◽

Oxidative Dna Damage ◽

Acute Inflammation ◽

Tissue Injury ◽

Multiple Organ ◽

Stingless Bee ◽

Ameliorative Effect ◽

Pro Inflammatory Cytokines

Background: Systemic acute inflammation is the hallmark of sepsis and associated with multiple organ dysfunction. Objective: This study investigated the potential of stingless bee honey (SBH) to suppress lipopolysaccharide (LPS)-induced systemic acute inflammation in rats and to reveal the probable mechanism of action. Methods: Rats received 4.6 and 9.2 g/kg SBH for 7 days followed by a single injection of LPS and samples were collected after 6 h. Results: LPS induced liver, kidney, heart and lung injury manifested by increased serum transaminases, alkaline phosphatase, creatine kinase, creatinine and urea, along with multiple histological alterations, particularly, leukocyte infiltrations. Pro-inflammatory cytokines were elevated in serum, and NF-κB p65, p38 MAPK and HMGB-1 were significantly increased in different tissues of LPS-challenged rats. SBH prevented tissue injury, ameliorated pro-inflammatory cytokines, and suppressed NF-κB p65, p38 MAPK and HMGB-1 in rats received LPS. In addition, SBH diminished reactive oxygen species (ROS) production, lipid peroxidation and oxidative DNA damage, and enhanced glutathione and Nrf2 in LPS-induced rats. Conclusion: SBH prevents systemic acute inflammation by suppressing NF-κB, p38 MAPK, HMGB-1, oxidative stress and tissue injury in rats. Thus, SBH may represent an effective anti-inflammatory nutraceutical, pending further mechanistic studies.

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MO596HYPERPHOSPHATEMIA INDUCES ENDOTHELIN-1 SYNTHESIS AND INFLAMMATION IN LUNG FIBROBLASTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab089.009 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Ana Asenjo-Bueno ◽

Elena Alcalde-Estevez ◽

Gemma Olmos ◽

Diego Rodríguez-Puyol ◽

Maria Piedad Ruiz-Torres ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Function ◽

Real Time ◽

Chronic Diseases ◽

Inflammatory Cytokines ◽

Real Time Pcr ◽

Lung Fibroblasts ◽

Ros Production ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract Background and Aims Hyperphosphatemia is an aging-related condition associated to chronic diseases such as chronic kidney disease (CKD). In both cases, aging and CKD, it has been described a decline lung function, however, relationship between high serum levels of phosphate and lung damage has not been described yet. The aim of this work was to evaluate if phosphate could induce inflammation in lung, studying the mechanisms implied. Method In vitro studies were performed on a cell line from human lung fibroblasts (Wi-38) which were treated with a phosphate donor termed β-glycerophosphate (BGP, 10 mM) and also with endothelin 1 (ET-1, 10 nM) at different times. To assess inflammation, the expression of several cytokines such as TNF-α,IL-1β, IL-6 and MCP-1 were measured by real time PCR. mRNA expressions of prepro-ET-1 and endothelin-converting enzyme-1 (ECE-1) were also analyzed by real time PCR. Reactive oxygen species (ROS) production was evaluated by confocal microscopy in live cells using the fluorogenic probe CellROX as oxidative stress reagent. Results Treatment with BGP induced a significant rise of the pro-inflammatory cytokines expression, TNF-α, IL-1β, IL-6 and MCP-1, on lung fibroblasts. Moreover, BGP was able to regulate ET-1 system, as we found a significant increase of mRNA expressions not only of prepro-ET-1 but also of ECE-1, reaching a peak around 2 and 6 hours, respectively. Later, it was checked whether ET-1 could induce inflammation itself in lung fibroblasts. Cells incubated with ET-1 show similar results as BGP, increasing expressions of all cytokines, TNF-α, IL-1β, IL-6 and MCP-1.ET-1 response was earlier than BGP, around at 2 hours with ET-1 instead of at 8 hours with BGP. In order to elucidate a possible mechanism, ROS production was assessed after BGP treatment. BGP induced ROS production at 15 min in lung fibroblasts. Conclusion BGP induces the synthesis of pro-inflammatory cytokines as well as the system of synthesis of ET-1, besides to rise ROS production.ET-1 itself also increases pro-inflammatory cytokines expression. ET-1 could contribute to the inflammation observed in lung fibroblast after BGP treatment. We propose oxidative stress as a potential mechanism implied, as it is well known that ROS can mediate in inflammation and in the ET system. However, more studies are necessary to confirm this role. All in all, these results relate hyperphosphatemia with a higher inflammation in lung fibroblasts which could decline lung function in chronic diseases associated to aging as CKD.

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Angiotensin II induced pro‐inflammatory cytokines and oxidative stress in the brain are attenuated in mice lacking the gene for TNF‐α

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.805.12 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Srinivas Sriramula ◽

Joseph Francis

Keyword(s):

Oxidative Stress ◽

Angiotensin Ii ◽

Inflammatory Cytokines ◽

Tnf Α ◽

The Brain ◽

And Oxidative Stress ◽

Pro Inflammatory Cytokines

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Inhibition of Pro-Inflammatory Cytokine Secretion by Select Antioxidants in Human Coronary Artery Endothelial Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000520 ◽

2020 ◽

Vol 90 (1-2) ◽

pp. 103-112 ◽

Cited By ~ 1

Author(s):

Michael J. Haas ◽

Marilu Jurado-Flores ◽

Ramadan Hammoud ◽

Victoria Feng ◽

Krista Gonzales ◽

...

Keyword(s):

Endothelial Cells ◽

Ascorbic Acid ◽

Coronary Artery ◽

Inflammatory Cytokines ◽

Inflammatory Cytokine ◽

Culture Media ◽

Cytokine Secretion ◽

Human Coronary Artery ◽

Tnf Α ◽

Pro Inflammatory Cytokines

Abstract. Inflammatory and oxidative stress in endothelial cells are implicated in the pathogenesis of premature atherosclerosis in diabetes. To determine whether high-dextrose concentrations induce the expression of pro-inflammatory cytokines, human coronary artery endothelial cells (HCAEC) were exposed to either 5.5 or 27.5 mM dextrose for 24-hours and interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF α) levels were measured by enzyme immunoassays. To determine the effect of antioxidants on inflammatory cytokine secretion, cells were also treated with α-tocopherol, ascorbic acid, and the glutathione peroxidase mimetic ebselen. Only the concentration of IL-1β in culture media from cells exposed to 27.5 mM dextrose increased relative to cells maintained in 5.5 mM dextrose. Treatment with α-tocopherol (10, 100, and 1,000 μM) and ascorbic acid (15, 150, and 1,500 μM) at the same time that the dextrose was added reduced IL-1β, IL-6, and IL-8 levels in culture media from cells maintained at 5.5 mM dextrose but had no effect on IL-1β, IL-6, and IL-8 levels in cells exposed to 27.5 mM dextrose. However, ebselen treatment reduced IL-1β, IL-6, and IL-8 levels in cells maintained in either 5.5 or 27.5 mM dextrose. IL-2 and TNF α concentrations in culture media were below the limit of detection under all experimental conditions studied suggesting that these cells may not synthesize detectable quantities of these cytokines. These results suggest that dextrose at certain concentrations may increase IL-1β levels and that antioxidants have differential effects on suppressing the secretion of pro-inflammatory cytokines in HCAEC.

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