Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Aljobaily, Nouf; Viereckl, Michael J; Hydock, David S.; Aljobaily, Hend; Wu, Tsung-Yen; Busekrus, Raquel B.; Jones, Brandon C.; Alberson, Jammie; Han, Yuyan

doi:10.3390/nu13010041

Cited by 58 publications

(47 citation statements)

References 47 publications

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“…Secondly, supplementing the diet with Cr, one of another parameter in WD index, can relieve liver damage rely on inhibiting liver in ammation, oxidative stress and cellular senescence. 25 Copper ions are an oxidant and may cause obvious increase of oxidative stress and creatine consuption in WD patients whose body have excessive copper deposits, in our study, which may be the reason why the WD patients' serum Cr is lower than that of other liver diseases. But whether this is a ubiquitous phenomenon in all WD patients remains unclear.…”

Section: Discussionmentioning

confidence: 54%

Correlation Factors and a Predictive Model of Serum Ceruloplasmin Normalized Wilson’s Disease

Chen

Wang

et al. 2021

Preprint

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Background: The false increase of ceruloplasmin (Cp) in some Wilson’s disease (WD) patients, which overlaps with those in non-WD liver disease patients, decrease the diagnostic accuracy. The aims of our study was to understand the factors affecting WD patients’ Cp normalization, and develop a model using routine predictors to identify WD patients with ambiguous serum Cp.Results: The mixed effects model analysis which executed in longitudinal study revealed that the WD patients’ Cp normalization were significantly associated with the copper burden and liver function indexes, like urinary copper treated with dimercaptopropansulfonate sodium (P=0.000), aspartate aminotransferase (P=0.011), γ-glutamyltransferase (P=0.000), albumin (P=0.000). Multivariate logistic regression analysis in case-control study showed age (P=0.000) and serum creatine (P=0.000) were independent risk factors associated with WD. Based on their regression coefficients, a simplified WD index was derived: 0.001 × age [yr] × Creatine [umol/L]. The AUC value of WD index in total cohort were 0.923 (P=0.000). At a WD index cutoff value of ≤ 1.9 and ≤ 2.5, the positive and negtive predictive value are 88.2% and 89.9% for WD, respectively.Conclusions: The increase of serum Cp in WD patients is related to their excessive copper burden and hepatic injury, common tests can effectively foretell those WD patients with nearly normal serum Cp from other liver injury patients.

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Section: Discussionmentioning

confidence: 54%

Correlation Factors and a Predictive Model of Serum Ceruloplasmin Normalized Wilson’s Disease

Chen

Wang

et al. 2021

Preprint

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“…Proline can metabolize and produce electrons, and generate reactive oxygen species, leading to a variety of downstream effects, including blocking cell cycles, autophagy, and apoptosis ( Selen et al, 2015 ). Creatine can alleviate liver injuries by inhibiting liver inflammation, oxidative stress, and cell senescence ( Deminice et al, 2016 ; Aljobaily et al, 2020 ). Creatine can also reduce the consumption of adenosylmethionine and the production of homocysteine in the liver, lowering the damage to homocysteine metabolism in the liver and the accumulation of lipids ( Barcelos et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Yang

Jin

et al. 2021

Front. Pharmacol.

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Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

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“…Creatine plays a role in the antioxidant role against aqueous radical and reactive species ions ( Lawler et al, 2002 ). The supplementation in creatine protects the liver from hepatotoxicity by attenuating oxidative stress ( Aljobaily et al, 2021 ). Lo et al (2020a) showed that, in overfed liver duck, an increase in liver weight resulted in a rise in the cellular oxidative stress level ( Lo et al, 2020a ).…”

Section: Discussionmentioning

confidence: 99%

Application of Metabolomics to Identify Hepatic Biomarkers of Foie Gras Qualities in Duck

Mozduri

Marty-Gasset

et al. 2021

Front. Physiol.

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Foie gras is a traditional dish in France that contains 50 to 60% of lipids. The high-fat content of the liver improves the organoleptic qualities of foie gras and reduces its technological yield at cooking (TY). As the valorization of the liver as foie gras products is strongly influenced by the TY, classifying the foie gras in their potential technological quality before cooking them is the main challenge for producers. Therefore, the current study aimed to identify hepatic biomarkers of foie gras qualities like liver weight (LW) and TY. A group of 120 male mule ducks was reared and overfed for 6–12 days, and their livers were sampled and analyzed by proton nuclear magnetic resonance (1H-NMR). Eighteen biomarkers of foie gras qualities were identified, nine for LW and TY, five specific to LW, and four specific to TY. All biomarkers were strongly negatively correlated to the liver weights and positively correlated to the technological yield, except for the lactate and the threonine, and also for the creatine that was negatively correlated to foie gras technological quality. As a result, in heavy livers, the liver metabolism was oriented through a reduction of carbohydrate and amino acid metabolisms, and the plasma membrane could be damaged, which may explain the low technological yield of these livers. The detected biomarkers have been strongly discussed with the metabolism of the liver in nonalcoholic steatohepatitis.

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Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Cited by 58 publications

References 47 publications

Correlation Factors and a Predictive Model of Serum Ceruloplasmin Normalized Wilson’s Disease

Correlation Factors and a Predictive Model of Serum Ceruloplasmin Normalized Wilson’s Disease

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Application of Metabolomics to Identify Hepatic Biomarkers of Foie Gras Qualities in Duck

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