β‐Hydroxybutyrate exacerbates lipopolysaccharide/<scp>d</scp>‐galactosamine‐induced inflammatory response and hepatocyte apoptosis in mice

Yang, Yongqiang; Shao, Ruyue; Jiang, Rong; Zhu, Min; Tang, Li; Li, Longjiang; Zhang, Li

doi:10.1002/jbt.22372

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Liver of LPS/D-Gal-treated mice often show apoptosis and necroptosis ( 35 ); we next investigated whether Pa or SA-Pa treatment could alleviate these cell deaths. TUNEL staining, which labels the exposed DNA termini due to apoptosis ( 36 ), showed that SA-Pa, but not Pa, treatment significantly reduced the injury-induced incidence of hepatocyte apoptosis ( Figure 6A and Supplementary Figure 3A ).…”

Section: Resultsmentioning

confidence: 99%

Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury

Xie

Qin

et al. 2022

Front. Immunol.

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Acute liver injury (ALI) is a life-threatening syndrome with high mortality and lacks effective therapies. Rodents under LPS (lipopolysaccharide)/D-Gal (D-galactosamine) stress mimic ALI by presenting dramatically increased inflammation and cell death in the liver. Euglena gracilis, functioning like dietary fiber, is commonly used as a paramylon (Pa)-rich nutritional supplement that has various biological effects such as regulating immune system, anti-obesity, and anti-tumor. Here, we found that Pa or sonicated and alkalized paramylon (SA-Pa) alleviated the LPS/D-Gal-induced hepatic histopathological abnormalities in mice. Compared with Pa, SA-Pa had lower molecular weights/sizes and showed better efficacy in alleviating injury-induced hepatic functions, as well as the transcriptional levels of inflammatory cytokines. Moreover, SA-Pa treatment promoted M2 macrophage activation that enhanced the anti-inflammatory function in the liver, and downregulated STAT3 target genes, such as Fos, Jun, and Socs3 upon the injury. Meanwhile, SA-Pa treatment also alleviated apoptosis and necroptosis caused by the injury. Our results demonstrated that SA-Pa efficiently protected the liver from LPS/D-Gal-induced ALI by alleviating inflammation and cell death.

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Section: Resultsmentioning

confidence: 99%

Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury

Xie

Qin

et al. 2022

Front. Immunol.

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“…Thus, the protective effects of β-HB may be mediated through metabolic signals by enhancing mitochondrial function for ATP generation. However, one report found that hepatocyte injury and apoptosis in mice with acute inflammation models induced by LPS and D-galactosamine were further exacerbated by β-HB administration [ 20 ]. The specific reasons may be related to the characteristics of different disease models, the mode of β-HB treatment and the therapeutic dose of β-HB, and further experimental investigation is required.…”

Section: Discussionmentioning

confidence: 99%

β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis

Tian,

Tang,

Zhao

et al. 2024

Renal Failure

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Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of β-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or β-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of β-HB on cisplatin-induced AKI. Exogenous or endogenous β-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo . Additionally, β-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. β-HB also improved mitochondrial morphology and function. Moreover, β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro . Furthermore, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by β-HB. This study provided evidence of the protective effects of β-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms.

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“…There may be a narrow and unique therapeutic window of BHB concentrations . BHB has been shown to enhance inflammation and apoptosis in the liver and enhance the cytotoxic effect of cisplatin in human hepatocellular carcinoma cells, , whereas it has displayed anti-inflammatory effects in other studies. , Moreover, it is reported that high BHB levels experienced increases in serum LDL cholesterol levels and the concentrations of HDL after medium-chain triglycerides (MCT) treatment, effective strategies to increase blood levels of the BHB, and intervention were significantly decreased. , Both high LDL levels and low HDL levels are considered risk factors for ischemic stroke. Thus, we suppose that the possible toxic effects and decreased effectiveness of high doses of BHB may be due to increased effects of BHB on cholesterol metabolism and the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Rational Application of β-Hydroxybutyrate Attenuates Ischemic Stroke by Suppressing Oxidative Stress and Mitochondrial-Dependent Apoptosis via Activation of the Erk/CREB/eNOS Pathway

Yang

Zhang

et al. 2021

ACS Chem. Neurosci.

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Stroke is one of the leading causes of disability and death. Increasing evidence indicates that β-hydroxybutyrate (BHB) exerts beneficial effects in treating stroke, but the underlying mechanism remains largely unknown. In this study, we injected different doses of BHB into the lateral ventricle in middle cerebral artery occlusion (MCAO) model rats and neuronal cells were treated with different doses of BHB followed by oxygen-glucose deprivation (OGD). We found that a moderate dose of BHB enhanced mitochondrial complex I respiratory chain complex I activity, reduced oxidative stress, inhibited mitochondrial apoptosis, improved neurological scores, and reduced infarct volume after ischemia. We further showed that the effects of BHB were achieved by upregulating the dedicated BHB transporter SMCT1 and activating the Erk/CREB/eNOS pathway. These results provide us with a foundation for a novel understanding of the neuroprotective effects of BHB in stroke.

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β‐Hydroxybutyrate exacerbates lipopolysaccharide/d‐galactosamine‐induced inflammatory response and hepatocyte apoptosis in mice

Cited by 6 publications

References 39 publications

Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury

Paramylon from Euglena gracilis Prevents Lipopolysaccharide-Induced Acute Liver Injury

β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis

Rational Application of β-Hydroxybutyrate Attenuates Ischemic Stroke by Suppressing Oxidative Stress and Mitochondrial-Dependent Apoptosis via Activation of the Erk/CREB/eNOS Pathway

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