Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock

Toyosawa, Toshio; Suzuki, Mamoru; Kodama, Kazuhisa; Araki, Seiichi

doi:10.1128/iai.72.3.1820-1823.2004

Cited by 47 publications

(42 citation statements)

References 17 publications

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“…36 However, RF is known to exert anti-inflammatory activity by reducing or inhibiting proinflammatory mediators such as TNFα, IL-1β, IL-6, IFNγ in several experimental models. 12,18,20 Accordingly, our data revealed that RF treatments reversed the low levels of COL1A1 and COL3A1 protein expressions due to colitis induction most probably through the inhibition of these proinflammatory mediators, thus protecting the functions of the immunological barrier, which effectively exert an anti-inflammatory role in the colonic mucosa.…”

Section: Discussionmentioning

confidence: 59%

“…tumor necrosis factor (TNF)α, interleukin (IL)-1β, IL-6, interferon (IFN)γ, monocyte chemotactic protein-1 and nitric oxide] in a murine model of sepsis and septic shock. 12 More recently, it was reported that administration of soymilk fermented by the RF-producing Lactobacillus plantarum strain to mice showed antiinflammatory effects by lowering microbial translocation to liver and decreasing cytokine levels in intestinal fluids in a trinitrobenzene sulfonic acid-induced intestinal inflammation model. 18 Furthermore, RF caused a protective effect by reversing cellular changes such as interstitial edema, haemorrhage and polymorphonuclear leukocyte infiltration against lipopolysaccharide-induced acute lung injury.…”

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confidence: 99%

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Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Karakoyun

Ertaş

Yüksel

et al. 2017

Clin Exp Pharma Physio

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Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-β1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Karakoyun

Ertaş

Yüksel

et al. 2017

Clin Exp Pharma Physio

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“…In addition, the latter folate derivative is necessary for nucleic acid synthesis. Supraphysiological doses of vitamin B12 and vitamin B2, a cofactor of MTHFR, are beneficial in sepsis (7,8). Lipopolysaccharide (LPS) is a major cell-wall constituent of Gramnegative bacteria.…”

Section: Introductionmentioning

confidence: 99%

Methionine metabolism in an animal model of sepsis

Semmler¹,

Smulders²,

Struys³

et al. 2008

Clinical Chemistry and Laboratory Medicine

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Background: Sepsis is a disease with high incidence and lethality and is accompanied by profound metabolic disturbances. In mammalian methionine metabolism, S-adenosylmethionine (SAM) is produced, which is important in the synthesis of neurotransmitters and glutathione and as an anti-inflammatory agent. The degradation product and antagonist of SAM is S-adenosylhomocysteine (SAH). In this study, we investigated changes in methionine metabolism in a rodent model of sepsis. Methods: Sepsis was induced in male Wistar rats (ns21) by intraperitoneal injection of bacterial lipopolysaccharide (10 mg/kg). Controls (ns18) received vehicle only. Blood was collected by cardiac puncture 24 h later. Puncture of the suboccipital fossa was performed to collect cerebrospinal fluid (CSF). Methionine metabolites were measured using stable isotope dilution tandem mass spectrometry. Plasma total homocysteine and cysteine were measured by HPLC using fluorescence detection. Glutathione was assayed using a modified enzymatic microtiter plate assay. Results: We observed significantly higher plasma levels of SAM (p-0.001) and SAM/SAH ratio (ps0.004) in septic animals. In CSF, there was also a trend for higher levels of SAM in septic animals (ps0.067). Oxidative stress was reflected by an increase in the ratio of oxidized/reduced glutathione in septic animals (ps0.001). Conclusions: Sepsis is associated with an increase in SAM/SAH ratio in plasma and CSF in rodents. This indicates an altered methylation potential during sepsis, which may be relevant for sepsis-associated

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“…Pyruvate is a physiological product of glucose metabolism that has been shown to be beneficial in experimental models of stroke, hemorrhagic shock, and cardiac, hepatic or mesenteric ischemia and reperfusion [130–132]. The beneficial effects of pyruvate are based on its positive myocardial inotropic effects by acting as an energy source, and a potential antioxidant and anti-inflammatory capability [131–133]. Despite its potential benefits, pyruvate is not stable in solution and rapidly undergoes an aldol-like condensation reaction to form parapyruvate, which can spontaneously convert to 2, 4-dihydroxy-2-methylglutarate, a mitochondrial poison [134, 135].…”

Section: Pharmacological Inhibition Of High Mobility Group Box 1 (Hmgb1)mentioning

confidence: 99%

Scientific and Clinical Challenges in Sepsis

Ulloa

Brunner

Ramos

et al. 2009

CPD

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Advances in intensive care and antibiotics have prevented the spread of some infections, though sepsis mortality rates remain high. With failure of over thirty clinical trials, sepsis remains a scientific and clinical challenge in modern medicine. Sepsis is defined by the clinical signs of a systemic inflammatory response to infection. “Severe sepsis” is when these symptoms are associated with multiple organ dysfunction. These definitions of sepsis may be too broad and common to heterogeneous groups of patients who do not necessarily have the same disorder. This consideration has become especially evident in the clinical trials that have failed to obtain consistent results in similar studies of patients diagnosed with severe sepsis. In these trials, patients with infections caused by different microorganisms, and affecting different organs, have been combined under the general diagnosis of severe sepsis. The situation is analogous to attempting a clinical trial based on the general definition of cancer, combining all patients with tumor independent of the type of malignancy. In this consideration, it would not be very surprising that activated protein C, the only treatment in sepsis approved by the Food and Drug Administration, is projected for use in only a small subset of patients with severe sepsis. This article reviews novel inflammatory molecular aspects and the experimental anti-inflammatory strategies for sepsis, as they may represent particular pathological processes in specific subsets of patients.

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Highly Purified Vitamin B2 Presents a Promising Therapeutic Strategy for Sepsis and Septic Shock

Cited by 47 publications

References 17 publications

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Methionine metabolism in an animal model of sepsis

Scientific and Clinical Challenges in Sepsis

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