Liver Fibrosis Can Be Induced by High Salt Intake through Excess Reactive Oxygen Species (ROS) Production

Wang, Guang; Yeung, Cheung Kwan; Wong, W. Y.; Zhang, Nuan; Yi, Wei; Zhang, Jing Li; Yan, Yu; Wong, Ching Yee Oliver; Tang, Jun; Chuai, Manli; Lee, Kenneth K.; Wang, Lijing; Yang, Xuesong

doi:10.1021/acs.jafc.5b05897

Cited by 39 publications

(27 citation statements)

References 38 publications

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“…Excess salt consumption adversely affects cardiovascular and renal physiology, and to a lesser known extent, liver physiology. Ingestion of high salt (4% NaCl in drinking water) by mice and exposure of chick embryos to high salt lead to liver fibrosis and derangement of the hepatic cords, respectively ( Wang et al, 2016a ). A recent study reporting the adverse effect of salt on obesity notes that a high intake of salt activates the aldose reductase-fructokinase pathway in the liver and leads to endogenous fructose production ( Lanaspa et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

et al. 2018

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Dietary salt reduction and exercise are lifestyle modifications for salt‐sensitive hypertensives. While exercise has prominent metabolic effects, salt has an adverse effect on metabolic syndrome, of which hypertension is a hallmark. We hypothesized that dietary salt impacts metabolism in a salt‐sensitive model of hypertension. An untargeted metabolomics approach demonstrates lower circulating levels of the ketone body, beta‐hydroxybutyrate (βOHB), in high salt‐fed hypertensive rats. Despite the high salt intake, specific rescue of βOHB levels by nutritional supplementation of its precursor, 1,3‐butanediol, attenuates hypertension and protects kidney function. This beneficial effect of βOHB was likely independent of gut‐microbiotal and Th17‐mediated effects of salt and instead facilitated by βOHB inhibiting the renal Nlrp3 inflammasome. The juxtaposed effects of dietary salt and exercise on salt‐sensitive hypertension, which decrease and increase βOHB respectively, indicate that nutritional supplementation of a precursor of βOHB provides a similar benefit to salt‐sensitive hypertension as exercise. Support or Funding Information Funding from this work to BJ from the NHLBI (NIH) (HL143082) is gratefully acknowledged. Declaration of interests: Bina Joe and Saroj Chakraborty have an interest in U.S. Patent Application Serial No.: 62/665,690 filed on May 2, 2018 in this paper regarding nutritional intervention for salt‐sensitive hypertension for 1,3‐butanediol. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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Section: Discussionmentioning

confidence: 99%

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

et al. 2018

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“…Although the MCD diet model well replicates the histological features of the fibrosis observed in human NASH, its metabolic context differs from human NASH, as animals fed the MCD diet for prolonged periods lose body weight, show low blood glucose, low blood triglyceride (TG) and cholesterol, unchanged or increased serum adiponectin levels, and elevated peripheral insulin sensitivity, which is a metabolic profile opposite to the human disease ( Larter et al, 2008 ). In the present study, therefore, we modified the MCD model by combining it with high-salt loading, because high salt intake would enhance liver damage and fibrosis in these mice ( Wang et al, 2016 ). We also used RAMP2 knockout mice to shorten the feeding period by accelerating LSEC damage.…”

Section: Discussionmentioning

confidence: 99%

Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells

Yamauchi

Kamiyoshi

Koyama

et al. 2017

Heliyon

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Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE) reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD) diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water) to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

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“…First-strand cDNA was synthesized to a final volume of 25 μL using SuperScript III First—Strand Synthesis SuperMix (Invitrogen, USA). Following reverse transcription, PCR amplification of the cDNA was performed using chick specific primers as previously described [ 19 , 20 ]. Primer sequences are provided in S1 Fig .…”

Section: Methodsmentioning

confidence: 99%

Applying chlorogenic acid in an alginate scaffold of chondrocytes can improve the repair of damaged articular cartilage

Cheng

et al. 2018

PLoS ONE

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Damaged cartilage has very low regenerative potential which has led to the search for novel tissue-engineering approaches to help treat cartilage defects. While various approaches have been reported, there is no perfect treatment currently. In this study we evaluated the effects of a plant extract, chlorogenic acid (CGA), as part of chondrocyte transplantation on a model of knee joint injury in chicks. First, primary cultured chondrocytes used to evaluate the effects of CGA on chondrogenesis. Then using an articular cartilage injury model of chick knee we assessed the functional recovery after transplantation of the complexes containing chondrocytes and CGA in an alginate scaffold. Histological analysis, PCR, and western blot were further used to understand the underlying mechanisms. We showed that 60 μM CGA in alginate exhibited notable effects on stimulating chondrogenesis in vitro. Secondly, it was shown that the application of these complexes accelerated the recovery of injury-induced dysfunction by gait analysis when followed for 21 days. Histochemical analysis demonstrated that there was less abnormal vasculature formation, more chondrocyte proliferation and cartilage matrix synthesis in the presence of the complexes containing CGA. We discovered CGA treated transplantation up-regulated the expressions of Sox9 and Col2a1 which were responsible for the stimulation of chondrogenesis. Furthermore, the application of these complexes could suppress the abnormal angiogenesis and fibrosis at the injury site. Lastly, the elevated levels of inflammatory cytokines IL-1β, TNF-α, p-p65, and MMPs expression were decreased in the presence of CGA. This may be caused through adjusting cellular redox homeostasis associated with Nrf2. This study suggests that combining chondrocytes and CGA on an alginate scaffold can improve the recovery of damaged articular cartilage.

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Liver Fibrosis Can Be Induced by High Salt Intake through Excess Reactive Oxygen Species (ROS) Production

Cited by 39 publications

References 38 publications

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension

Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells

Applying chlorogenic acid in an alginate scaffold of chondrocytes can improve the repair of damaged articular cartilage

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