Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model

Gao, Min; Jiang, Yu; Xiao, Xiang; Peng, Yue; Xiao, Xianzhong; Yang, Mingshi

doi:10.1016/j.jss.2015.02.007

Cited by 23 publications

(16 citation statements)

References 44 publications

(38 reference statements)

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“…Serological indexes detection revealed that the levels of plasma DAO, D-LA and FABP2 in the alcohol model group were increased. The intact intestinal mucosa provides a barrier function to prevent DAO and D-LA from infiltrating the portal circulation, which are indexes of increases in permeability of the intestinal wall [37]. In this study, after aplysin intervention, the small intestine columnar epithelium and microvilli arrangement were improved, the swelling of tight connections was reduced, and the levels of plasma DAO and FABP2 were reduced.…”

Section: Discussionmentioning

confidence: 66%

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Xue¹,

Liu²,

Lyu³

et al. 2017

PLoS ONE

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BackgroundThis study investigated the protective effect of aplysin on the liver and its influence on inflammation and the gut microbiota in rats with ethanol-induced liver injury.MethodsMale Sprague-Dawley rats were randomly assigned to an alcohol-containing liquid diet, control liquid diet or treatment with aplysin for 8 weeks. Hepatic and intestinal histopathological analysis was performed, and cytokine levels and the intestinal mucosal barrier were assessed. Enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) and 16S rDNA high-throughput sequencing were performed to provide an overview of the gut microbiota composition.ResultsChronic alcohol exposure caused liver damage in rats. Serum aspartate aminotransferase (AST), aminotransferase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) activities in liver tissue were higher than in the control group. Alcohol administration elevated the levels of serum transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) and reduced interleukin-10 (IL-10) levels compared with those of control rats. In addition, the levels of plasma endotoxin, diamine oxidase (DAO), and fatty acid-binding protein 2 (FABP2) in the alcohol group were higher than in the control group. The results of ERIC-PCR indicated that aplysin treatment shifted the overall structure of the ethanol-disrupted gut microbiota toward that of the control group. One hundred twenty to 190 genera of bacteria were detected by high throughput sequencing. Alcohol-induced changes in the gut microbial composition were detected at the genus level. These alcohol-induced effects could be reversed with aplysin treatment.ConclusionsThese results suggest that aplysin exerts a protective effect on ethanol-induced hepatic injury in rats by normalizing fecal microbiota composition and repairing intestinal barrier function.

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Section: Discussionmentioning

confidence: 66%

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Xue¹,

Liu²,

Lyu³

et al. 2017

PLoS ONE

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“…Our study showed a significantly reduced ATP generation in animals with moderate and severe sepsis. While sepsis itself, via oxidative stress (11) inhibits electron transport chain complexes activity (20), another pathway for ATP generation independent of thiamin; in the present study, the reduced MTPPT protein or mRNA expressions contributed to the reduced ATP production. Levels of MTPPT protein and mRNA expressions were responsible for 50% of the variance in ATP production as shown in the significant correlation between ATP production and MTPPT protein and mRNA expression levels (r 2 = 0.50; P < 0.01 for MTPPT protein; and r 2 = 0.54; P < 0.01 for MTTPT mRNA expression, respectively).…”

Section: Discussionmentioning

confidence: 48%

“…Gut-derived sepsis, the sepsis model employed, has been shown to impair intestinal epithelial barrier function to promote bacterial translocation into the systemic circulation with subsequent bacteremia, and pathologic inflammation of the intestinal mucosa (11). Whether inflammation of the intestinal mucosa alone with or without adherence of the organisms to the intestinal epithelium is a requirement for thiamin uptake inhibition is unclear.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

Sassoon

Zhu

Fang

et al. 2016

Critical Care Medicine

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Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion.

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“…193 Administration of the PPARγ agonists, rosiglitazone and pioglitazone (but not WY-14643, a PPARα agonist) have been shown to reduce mortality in rodents subjected to sepsis. 194,195 Like PPARα, PPARγ modulates metabolism and is upregulated by HIF-1 in the setting of hypoxia. 196 …”

Section: Therapeutic Applications Targeting Subcellular Energeticsmentioning

confidence: 99%

Subcellular Energetics and Metabolism: Potential Therapeutic Applications

Thiele

2017

Anesthesia &Amp; Analgesia

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Part I of this review discussed the similarities between embryogenesis, mammalian adaptions to hypoxia (primarily driven by Hypoxia Inducible Factor-1 [HIF-1]), ischemia-reperfusion injury (and its relationship with reactive oxygen species), hibernation, diving animals, cancer, and sepsis, and focused on the common characteristics that allow cells and organisms to survive in these states. Part II of this review describes techniques by which researchers gain insight into subcellular energetics and identify potential future tools for clinicians. In particular, P31 nuclear magnetic resonance to measure high energy phosphates, serum lactate measurements, the use of near infrared spectroscopy to measure the oxidation state of cytochrome aa3, and the ability of the protoporphyrin IX-triplet state lifetime technique to measure mitochondrial oxygen tension are discussed. Additionally, this review will discuss novel treatment strategies such as hyperbaric oxygen, preconditioning, exercise training, therapeutic gases, as well as inhibitors of HIF-1, HIF prolyl hydroxylase (PHD), and Peroxisome proliferator-activated receptors (PPARs).

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Protective effect of pioglitazone on sepsis-induced intestinal injury in a rodent model

Cited by 23 publications

References 44 publications

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Protective effect of aplysin on liver tissue and the gut microbiota in alcohol-fed rats

Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

Subcellular Energetics and Metabolism: Potential Therapeutic Applications

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