Oxidative Stress Is Associated with Poor Prognosis in Patients with Follicular Lymphoma

Abstract [Introduction] Follicular lymphoma (FL) is an indolent non-Hodgkinfs lymphoma (NHL), with a highly variable clinical course that can range from indolent to rapidly progressive disease, including the transformation to aggressive NHL. Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of oxidative stress in FL is still unknown. The objective of this study is to evaluate the role of oxidative stress in patients with FL. [Methods] 8-hydroxy-2-deoxyguanosine (8-OHdG), which originates from damaged DNA repaired by non-specific endonucleases and specific glycosylates and is eliminated into urine, is widely used as a sensitive biomarker of oxidative stress. Urinary 8-OHdG levels have been reported to be elevated in patients with various malignancies. In the present study, urinary 8-OHdG levels were prospectively examined in 30 patients with FL by using a novel automatic oxidative stress analyzer, ICR-001. We also evaluated serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki. [Results] Median age at diagnosis was 70 years (range, 43-84 years) and 53% were male. According to the WHO pathological grading, grade 1 FL was observed in 16 patients (53%), grade 2 FL in 8 patients (27%), and grade 3 FL in 6 patients (20%). FLIPI scores were 0 to 1 in 27%, 2 in 27%, and 3 to 5 in 46%. The urinary 8-OHdG levels in patients with FL (N=30) were elevated compared with normal controls (N=20) (19.7+/-10.3 vs. 13.7+/-3.4 ng/mg/Cr, P=0.01). In 30 FL patients, patients with high urinary 8-OHdG levels (over 23.9 ng/mg/Cr) had significantly shorter overall survival (OS) than those with low urinary 8-OHdG levels (under 23.9 ng/mg/Cr) (3-year OS, 33.3% versus 90.5%, respectively; P<0.001) (Figure. 1). The serum d-ROMs levels in patients with FL were significantly elevated compared with normal controls (543.9+/-199.4 vs. 281.1+/-25.9 CARR U, P<0.001). Patients with high serum d-ROMs levels (over 519 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (under 519 CARR U) (3-year OS, 41.7% versus 94.4%, respectively; P<0.001) (Figure. 2). In univariate analysis, high 8-OHdG levels, high d-ROMs levels, high PS, high LDH levels, high tumor burden (GELF criteria), high beta-2 microglobulin levels, and high FLIPI score were associated with poor OS in patients with FL. In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (over 519 CARR U) (p=0.01, HR 15.68), high LDH levels (p=0.02, HR 12.25). [Conclusion] In the present study we demonstrated that elevated urinary 8-OHdG levels and serum d-ROMs levels are associated with poor prognosis in patients with FL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with FL. These results suggest that oxidative stress may have an important role in FL and also may be a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. Disclosures Nakazato: Mundipharma KK: Research Funding.

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Serum Reactive Oxygen Metabolite Levels Are Associated with Poor Prognosis in Patients with Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-111874 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1704-1704

Author(s):

Shinji Ogura ◽

Takahiro Kamiya ◽

Kota Mizuno ◽

Chisako Ito ◽

Yuriko Fujita ◽

...

Keyword(s):

Oxidative Stress ◽

Poor Prognosis ◽

Cell Lymphoma ◽

Reactive Oxygen ◽

B Cell Lymphoma ◽

High Serum ◽

Reactive Oxygen Metabolites ◽

Large B Cell Lymphoma ◽

Oxygen Metabolites

Abstract [Introduction] Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of serum reactive oxygen metabolites (ROMs) in DLBCL is still unknown. The objective of this study is to evaluate the role of serum ROMs in patients with DLBCL. [Methods] We enrolled 52 patients with DLBCL who were treated at our institution between 2012 and 2014. To assess oxidative stress, instead of measuring serum ROS directly, we measured serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels. In the present study, serum d-ROMs levels were prospectively examined in 52 patients with DLBCL and 12 healthy subjects by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki. [Results] The median follow-up time was 52 months. Median age at diagnosis was 74 years (range, 39-91 years) and 60% were male. 34 patients (65%) were stage 3-4 and 33 patients (63%) were R-IPI poor risk. The serum d-ROMs levels in patients with DLBCL were significantly elevated compared with normal controls (578.9+/-194.3 vs. 286.8+/-24.2 CARR U, P<0.001). In 52 DLBCL patients, patients with high serum d-ROMs levels (≥513 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (<513 CARR U) (5-year OS, 37.9% versus 77.7%, respectively; P<0.001) (Figure. 1). In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (≥513 CARR U) (p=0.002, HR 5.17), high LDH levels (p=0.008, HR 4.58), and extranodal involvement >1 (p=0.002, HR 4.57). [Conclusion] In the present study we demonstrated that elevated serum d-ROMs levels are associated with poor prognosis in patients with DLBCL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with DLBCL. These results suggest that oxidative stress may have an important role in DLBCL and may be also a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. Disclosures No relevant conflicts of interest to declare.

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Effects of Non-Surgical Periodontal Treatment on Reactive Oxygen Metabolites and Glycemic Control in Diabetic Patients with Chronic Periodontitis

Antioxidants ◽

10.3390/antiox10071056 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1056

Author(s):

Simone Marconcini ◽

Enrica Giammarinaro ◽

Saverio Cosola ◽

Giacomo Oldoini ◽

Annamaria Genovesi ◽

...

Keyword(s):

Oxidative Stress ◽

Glycemic Control ◽

Systemic Inflammation ◽

Glycated Hemoglobin ◽

Reactive Oxygen ◽

Periodontal Treatment ◽

Diabetic Patients ◽

Reactive Oxygen Metabolites ◽

Periodontal Infection ◽

Oxygen Metabolites

Background: Periodontal infection may contribute to poor glycemic control and systemic inflammation in diabetic patients. The aim of the present study is to evaluate the efficacy of non-surgical periodontal treatment in diabetic patients by measuring oxidative stress outcomes. Methods: Sixty diabetic patients with periodontitis were enrolled, treated with scaling and full-mouth disinfection, and randomly prescribed chlorhexidine mouthwash, antioxidant mouthwash, or ozone therapy. Reactive oxygen metabolites (ROMs), periodontal parameters, and glycated hemoglobin were measured at baseline and then at 1, 3, and 6 months after. Results: At baseline, all patients presented with pathologic levels of plasmatic ROM (388 ± 21.36 U CARR), higher than the normal population. Probing depth, plaque index, and bleeding on probing values showed significant clinical improvements after treatment, accompanied by significant reductions of plasma ROM levels (p < 0.05). At the 6-month evaluation, the mean ROM relapsed to 332 ± 31.76 U CARR. Glycated hemoglobin decreased significantly (∆ = −0.52 units) after treatment. Both the test groups showed longer-lasting improvements of periodontal parameters. Conclusion: In diabetic patients, periodontal treatment was effective at reducing plasma ROM, which is an indicator of systemic oxidative stress and inflammation. The treatment of periodontal infection might facilitate glycemic control and decrease systemic inflammation.

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S1639 Effect of Helicobacter pylori Infection on the Phenomenon of Gastric Mucosal Adaptation to Repetitive Aspirin Insult in Mongolian Gerbils. Role of Reactive Oxygen Metabolites and Proinflammatory Cytokines

Gastroenterology ◽

10.1016/s0016-5085(10)61109-2 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-244 ◽

Cited By ~ 1

Author(s):

Robert Pajdo ◽

Tomasz Brzozowski ◽

Peter Konturek ◽

Zbigniew Sliwowski ◽

Agata Ptak-Belowska ◽

...

Keyword(s):

Helicobacter Pylori ◽

Proinflammatory Cytokines ◽

Reactive Oxygen ◽

Helicobacter Pylori Infection ◽

Mongolian Gerbils ◽

Reactive Oxygen Metabolites ◽

Mucosal Adaptation ◽

Oxygen Metabolites

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Effect of Reactive Oxygen Metabolites on Endothelial Permeability: Role of Nitric Oxide and Iron

Microcirculation ◽

10.1111/j.1549-8719.1999.tb00093.x ◽

1999 ◽

Vol 6 (2) ◽

pp. 107-116 ◽

Cited By ~ 6

Author(s):

NAOTSUKA OKAYAMA ◽

MATTHEW B. GRISHAM ◽

CHRISTOPHER G. KEVIL ◽

LOIS ANN EPPIHIMER ◽

DAVID A. WINK ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Permeability ◽

Reactive Oxygen ◽

Reactive Oxygen Metabolites ◽

Oxygen Metabolites

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Role of reactive oxygen metabolites in DNA damage and cell death in chemical hypoxic injury to LLC-PK1 cells

AJP Renal Physiology ◽

10.1152/ajprenal.1996.271.1.f209 ◽

1996 ◽

Vol 271 (1) ◽

pp. F209-F215 ◽

Cited By ~ 8

Author(s):

H. Hagar ◽

N. Ueda ◽

S. V. Shah

Keyword(s):

Dna Damage ◽

Cell Death ◽

Reactive Oxygen ◽

Reactive Oxygen Metabolites ◽

Strand Breaks ◽

Hypoxic Injury ◽

Chemical Hypoxia ◽

Dna Strand ◽

Oxygen Metabolites

Hypoxia is considered to result in a necrotic form of cell injury. We have recently demonstrated a role of endonuclease activation, generally considered a feature of apoptosis, to be almost entirely responsible for DNA damage in hypoxic injury to renal tubular epithelial cells. The role of reactive oxygen metabolites in endonuclease-induced DNA damage and cell death in chemical hypoxic injury has not been previously examined. LLC-PK1 cells exposed to chemical hypoxia with antimycin A resulted in enhanced generation of intracellular reactive oxygen species as measured by oxidation of a sensitive fluorescent probe, 2',7'-dichlorofluorescin diacetate. Superoxide dismutase, a scavenger of superoxide radical, significantly reduced the fluorescence induced by antimycin A and provided significant protection against chemical hypoxia-induced DNA strand breaks (as measured by the alkaline unwinding assay). Pyruvate, a scavenger of hydrogen peroxide, provided significant protection against chemical hypoxia-induced DNA strand breaks and DNA fragmentation (as measured by agarose gel electrophoresis). The interaction between superoxide anion and hydrogen peroxide in the presence of a metal catalyst leads to generation of other oxidant species such as hydroxyl radical. Hydroxyl radical scavengers, dimethylthiourea, salicylate, and sodium benzoate, and two metal chelators, deferoxamine and 1,10-phenanthroline, also provided marked protection against DNA strand breaks and DNA fragmentation. These scavengers of reactive oxygen metabolites and metal chelators provided significant protection against cell death as measured by trypan blue exclusion and lactate dehydrogenase release. Taken together, these data indicate that reactive oxygen species play an important role in the endonuclease activation and consequent DNA damage, as well as cell death in chemical hypoxic injury to renal tubular epithelial cells.

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