The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis

Andrade, José Antenor Araújo de; Gayer, Carlos Roberto Machado; Nogueira, Natália Pereira de Almeida; Paes, Márcia Cristina; Bastos, V. L. F. Cunha; Neto, Jayme da Cunha Bastos; Alves, Sílvio Caetano; Coelho, Raphael Molinaro; Cunha, Mariana Gysele Amarante Teixeira da; Gomes, Rachel Novaes; Águila, Márcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto; Bozza, Patrı́cia T.; Cunha, Sérgio da

doi:10.1186/1476-9255-11-11

Cited by 56 publications

(34 citation statements)

References 48 publications

(52 reference statements)

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“…The present results indicated that the serum levels of inflammatory cytokines, biomarkers and inflammatory cells were upregulated in patients with sepsis compared with those in healthy individuals. Circulating inflammatory cytokines have been identified as mediators of damage in patients with sepsis (26). The present study reported the upregulation of the inflammatory cytokines IL-1, IL-17, TNF-α and IL-6 in sepsis patients compared with those in healthy individuals.…”

Section: Discussionsupporting

confidence: 47%

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

2018

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Abstract. Sepsis is a systemic inflammatory response syndrome caused by infection of bacteria, fungi and/or viruses in clinical patients. It is known that inflammatory cytokine levels have an essential role in the progression of sepsis. The present study investigated the role of inflammatory markers in human peripheral blood mononuclear cells (hPBMCs) of patients with sepsis at an intensive care unit. In addition, the plasma levels of inflammatory cytokines were compared between sepsis patients and healthy individuals. The results demonstrated that the serum levels of interleukin-1, -17 and -6, as well as tumor necrosis factor-α, were upregulated in sepsis patients. The serum levels of high mobility group box 1 and C-reactive protein were increased in sepsis patients compared with those in healthy individuals. The expression levels of nuclear factor-κB-p65 and its inhibitor IκBα, as well as the ratio of CD25 + cells, and the levels of neutrophil gelatinase-associated lipocalin and peptidoglycan recognition protein were higher in hPBMCs in sepsis patients compared with those in healthy individuals. It was also indicated that balance of T helper type 1/2 cytokines was also disturbed in patients with sepsis compared with that in healthy individuals. In conclusion, these results indicated that inflammation is involved in the progression of sepsis by interfering with the expression of various molecules, suggesting a potential therapeutic strategy for the treatment of sepsis patients.

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Section: Discussionsupporting

confidence: 47%

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

2018

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“…As suggested, the gut microbiota can establish efficient crosstalk with the rest of the body through a number of mediators. Interestingly, the metabolic end products of the [41,42] SCFAs [46] miRNAs [56] Indoxyl sulfate [43,44] NO [47] b Bile acids [50] TMAO [45] Vitamin K [51] N E [ 63] Oxalate [48,49] Vitamin B complex [17,[52][53][54] ANS [66,99] Serotonin [62] Threonine [55] ENS [67] GLP-1 [57] GLP-2 [58] PYY [59] GABA [60,61] ACh [65] Dopamine [64] H 2 S [87,88] a Some of these mediators have both pro-and anti-inflammatory effects…”

Section: The Gut Microbiota Regulates Inflammatory Processes Directlymentioning

confidence: 99%

“…The gut microbiota contributes to the health of the host by protective and trophic functions [6] in addition to aiding host metabolism by synthesizing conjugated linoleic acid [7], amino acids such as lysine [8], vitamin B complex [9], and vitamin K [10] and by facilitating the absorption of complex carbohydrates [11]. Additionally, the gut microbiota communicates with the rest of the body primarily via its interactions with the immune system [12] and its metabolic products, such as uremic toxins [2], oxalate [13], bile acids [14], short-chain fatty acids (SCFAs) [15], nitric oxide (NO) [16], vitamin K [10], vitamin B complex [17], threonine [18], microRNAs (miRNAs) [19], gut hormones [20], neurotransmitters [21], the autonomic nervous system (ANS), and the enteric nervous system (ENS) [22] and through effects on intestinal expression of cannabinoid receptor CB1 [23].…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

et al. 2018

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The health and proper functioning of the cardiovascular and renal systems largely depend on crosstalk in the gut-kidney-heart/vessel triangle. Recent evidence suggests that the gut microbiota has an integral function in this crosstalk. Mounting evidence indicates that the development of chronic kidney and cardiovascular diseases follows chronic inflammatory processes that are affected by the gut microbiota via various immune, metabolic, endocrine, and neurologic pathways. Additionally, deterioration of the function of the cardiovascular and renal systems has been reported to disrupt the original gut microbiota composition, further contributing to the advancement of chronic cardiovascular and renal diseases. Considering the interaction between the gut microbiota and the renal and cardiovascular systems, we can infer that interventions for the gut microbiota through diet and possibly some medications can prevent/stop the vicious cycle between the gut microbiota and the cardiovascular/renal systems, leading to a decrease in chronic cardiovascular and renal diseases.

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“…This result suggests that if P. aeruginosa relies solely on exogenous TPP for growth, the concentration should be higher than 25 µM. Reported TPP levels in mouse blood range from 0.3 to 1.2 µM, well below the TPP concentration sufficient to support growth of the thiL mutant (45,46). Consistent with these data, we found that the thiL mutant exhibited markedly reduced pathogenicity in a mouse infection model when compared with the wild-type strain (Figs 5-6).…”

Section: Discussionmentioning

confidence: 99%

ThiL is a valid antibacterial target that is essential for both thiamine biosynthesis and salvage pathway inPseudomonas aeruginosa

Kim

Lee

et al. 2020

Preprint

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Thiamine pyrophosphate (TPP) is an essential cofactor for various pivotal cellular processes in all living organisms, including bacteria. As thiamine biosynthesis occurs in bacteria but not humans, bacterial thiamine biosynthesis is an attractive target for antibiotic development. Among enzymes in the thiamine biosynthetic pathway, thiamine monophosphate kinase (ThiL) catalyzes the final step of the pathway, phosphorylating thiamine monophosphate (TMP) to produce TPP. In this work, we extensively investigated ThiL in Pseudomonas aeruginosa, a major pathogen of hospital-acquired infections. We demonstrated that thiL deletion abolishes not only thiamine biosynthesis but also thiamine salvage capability, showing growth defects of the ΔthiL mutant even in the presence of thiamine derivatives except TPP. Most importantly, the pathogenesis of the ΔthiL mutant was markedly attenuated compared to wild-type bacteria, with lower inflammatory cytokine induction and 10 3~1 0 4 times decreased bacterial load in an in vivo infection model where the intracellular TPP level is in the submicromolar range. In order to validate P. aeruginosa ThiL (PaThiL) as a new drug target, we further characterized its biochemical properties determining a Vmax of 4.0±0.2 nomol·min -1 and KM values of 111±8 and 8.0±3.5μM for ATP and TMP, respectively. A subsequent in vitro small molecule screening identified PaThiL inhibitors including 2

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The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis

Cited by 56 publications

References 48 publications

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

Inflammatory cytokine expression in patients with sepsis at an intensive care unit

Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease

ThiL is a valid antibacterial target that is essential for both thiamine biosynthesis and salvage pathway inPseudomonas aeruginosa

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