Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats

Tokuda, Yomei; Miura, Natsuko; Kobayashi, Misato; Hoshinaga, Yukiko; Murai, Atsushi; Aoyama, Hiroaki; Ito, Hiroyuki; Morita, Tatsuya; Horio, Fumihiko

doi:10.1016/j.nut.2014.07.009

Cited by 9 publications

(5 citation statements)

References 29 publications

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“…Vitamin C-deficient guinea pigs in response to endotoxemia induction have increased NF-κB responses in association with exaggerated systemic shock and impaired lung phosphatidylcholine biosynthesis [60], [61], [62], while dietary vitamin C supplementation attenuates endotoxemia and intestinal barrier defects [62]. Vitamin C-deficient ODS rats also demonstrate increased endotoxemia associated with increased liver inflammation and gut dysfunction [63], increased gastric mucosal lesions [64], acute phase responses [65], inflammatory chemokine and cytokines [66], and cytokine-induced neutrophil chemoattractant-1 (CINC-1) [66]. They also have increased LDL [67], decreased HDL [68] and impaired synthesis of apo-AI [69].…”

Section: Why Would Improved Vitamin C Status Decrease Endotoxemia In mentioning

confidence: 99%

The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome

2019

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Metabolic syndrome (MetS) is a constellation of cardiometabolic risk factors, which together predict increased risk of more serious chronic diseases. We propose that one consequence of dietary overnutrition is increased abundance of Gram-negative bacteria in the gut that cause increased inflammation, impaired gut function, and endotoxemia that further dysregulate the already compromised antioxidant vitamin status in MetS. This discussion is timely because “healthy” individuals are no longer the societal norm and specialized dietary requirements are needed for the growing prevalence of MetS. Further, these lines of evidence provide the foundational basis for investigation that poor vitamin C status promotes endotoxemia, leading to metabolic dysfunction that impairs vitamin E trafficking through a mechanism involving the gut-liver axis. This report will establish a critical need for translational research aimed at validating therapeutic approaches to manage endotoxemia—an early, but inflammation-inducing phenomenon, which not only occurs in MetS, but is also prognostic of more advanced metabolic disorders including type 2 diabetes mellitus, as well as the increasing severity of nonalcoholic fatty liver diseases.

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Section: Why Would Improved Vitamin C Status Decrease Endotoxemia In mentioning

confidence: 99%

The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome

2019

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“…We have previously demonstrated that the serum concentrations of proinflammatory cytokines, such as interleukin-6 (IL-6) and IL-1b, and acute phase proteins (APPs) were elevated in AsA-deficient ODS rats, and that AsA deficiency in ODS rats promoted the expressions of various hepatic genes encoding for APPs including C-reactive protein (CRP) and haptoglobin (4,5). These observations in AsA-deficient ODS rats are similar to the observations during low-grade inflammation induced by bacterial infection.…”

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confidence: 99%

Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats

Kawade

Tokuda

Tsujino

et al. 2018

Journal of Nutritional Science and Vitaminology

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The aim of this study was to verify the protective effects of ascorbic acid (AsA) against lipopolysaccharide (LPS)-induced sepsis. The study was conducted using osteogenic disorder Shionogi (ODS) rats, which are unable to synthesize AsA. Male ODS rats (6 wk old) were fed either an AsA-free diet (AsA-deficient group), a diet supplemented with 300 mg/ kg AsA (control group), or a diet supplemented with 3,000 mg/kg AsA (high-AsA group) for 8 d. On day 8, all the rats were intraperitoneally injected with LPS (15 mg/kg body weight). Forty-eight hours after the injection, the survival rates of the rats in the control (39%) and the high-AsA (61%) groups were significantly higher than that in the AsA-deficient group (5.5%). Next, we measured several inflammatory parameters during 10 h after administering LPS. At 6 h, elevated serum levels of markers for hepatic and systemic injuries were suppressed in rats fed AsA. Similarly, 10 h after LPS injection, the elevation in the serum levels of markers for renal injury were also suppressed proportionally to the amount of AsA in the diet. The elevated serum concentrations of TNFa and IL-1b by LPS in the AsAdeficient group decreased in groups fed AsA. Hematic TNFa mRNA levels at 6 h after the LPS injection were also lowered by feeding AsA. These results demonstrated that the dietary intake of AsA improved the survival rates and suppressed the inflammatory damage, in a dose-dependent manner, caused during sepsis induced by LPS in ODS rats.

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“…AsA deficiency was previously reported to be involved in liver inflammation (19,20). However, the mechanism by which SMP30 is released into EVs during acute liver injury remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Osteogenic disorder Shionogi rats (ODS rats) have a hereditary defect in AsA biosynthesis and are hence a useful model for investigation of the physiological roles of AsA (18). Several investigators have shown that AsA deficiency alters the hepatic gene expression of positive acute-phase proteins (APPs), such as haptoglobin and a-1-acid glycoproteins (AGP), increases the serum concentration of interleukin-6 (IL-6) (19,20). Furthermore, hepatic expression of the inflammatory chemokine, cytokine-induced neutrophil chemoattractant-1 (CINC-1), was stimulated in acute inflammation in ODS rats (21).…”

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confidence: 99%

Release of SMP30 in Extracellular Vesicles under Conditions of Ascorbic Acid Deficiency Is Involved with Acute Phase Response in ODS Rat

ARAKAWA,

INOUE,

ISHIGAMI

et al. 2023

J Nutr Sci Vitaminol

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Senescence marker protein-30 (SMP30) is a senescence marker molecule that exhibits lactonase activity in the ascorbic acid (AsA) biosynthesis pathway, except in primate mammals, including humans. Although numerous studies have shown that hepatic AsA deficiency causes acute-phase responses, details of the relationship between SMP30 expression and acute-phase responses in AsA-deficient conditions remain to be elucidated. Here, we investigated the effects of AsA deficiency on the relationship between SMP30 and acute liver injury in osteogenic disorder Shionogi (ODS) rats, which have a hereditary defect in AsA biosynthesis. Male-ODS rats (4 wk old) were pair-fed an AsA-free diet with distilled or 0.1% AsA-dissolved water for 14 d. Under AsA-deficient conditions, hepatic SMP30 protein level was decreased and liver injury markers, the serum aspartate aminotransferase/ alanine transaminase ratio and cytokine-induced neutrophil chemoattractant-1 (CINC-1) concentration, were elevated. In contrast, SMP30 protein level in extracellular vesicles (EVs) was significantly increased in addition to the positive acute proteins haptoglobin and asialoglycoprotein receptor 1 (ASGPR1), hepatic-derived specific markers expression under AsA-deficient conditions. AsA deficiency also activated signal transducer and activator of transcription 3 (STAT3) which is linked to EVs release in the liver. These results suggest that the release of SMP30 in EVs by AsA deficiency is involved with acute-phase responses.

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Ascorbic acid deficiency increases endotoxin influx to portal blood and liver inflammatory gene expressions in ODS rats

Cited by 9 publications

References 29 publications

The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome

The relationship between vitamin C status, the gut-liver axis, and metabolic syndrome

Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats

Release of SMP30 in Extracellular Vesicles under Conditions of Ascorbic Acid Deficiency Is Involved with Acute Phase Response in ODS Rat

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