Oxaloacetate Ameliorates Chemical Liver Injury via Oxidative Stress Reduction and Enhancement of Bioenergetic Fluxes

Kuang, Ye; Han, Xing; Xu, Mu; Wang, Yue; Zhao, Yuxiang; Yang, Qing

doi:10.3390/ijms19061626

Cited by 25 publications

(10 citation statements)

References 45 publications

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“…Our previous study showed that urantide could effectively inhibit the MAPK signalling pathway in the tissues of atherosclerotic rats ( 10 ). Studies have revealed that urantide has antioxidant and anti-inflammatory effects and served a key role in CCl 4 -induced ALI ( 33 – 36 ). The present results indicated that, after 1 week of preventive urantide administration, the serum levels of ALT and AST did not increase significantly.…”

Section: Discussionmentioning

confidence: 99%

Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway

Guo

Cui

et al. 2021

Mol Med Rep

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a number of drugs and other triggers can cause acute liver injury (ali) in clinical practice. Therefore, identifying a safe drug for the prevention of liver injury is important. The aim of the present study was to investigate the potential preventive effect and regulatory mechanism of urantide on carbon tetrachloride (ccl 4 )-induced ali by investigating the expression of components of the MaPK signalling pathway and the urotensin ii (uii)/urotensin receptor (uT) system. liver oedema and severe fatty degeneration of the cytoplasm were observed in ali model rats, and the serum alanine aminotransferase (alT) and aspartate aminotransferase (aST) levels were found to be significantly increased. Compared with those in the ali model group, alT and aST levels and the liver index did not significantly increase in each group given the preventive administration of urantide, and the liver tissue morphology was correspondingly protected. Moreover, the gene and protein expression levels of uii, G protein-coupled receptor (GPr14) and the oxidative stress-sensitive cytokines, α-smooth muscle actin and osteopontin were decreased, indicating that the protein translation process was effectively maintained. However, the expression levels of MaPK signalling pathway-related proteins and genes were decreased. it was found that urantide could effectively block the MaPK signalling pathway by antagonizing the uii/uT system, thus protecting the livers of ali model rats. Therefore, it was suggested that ali may be associated with the MaPK signalling pathway, and effective inhibition of the MaPK signalling pathway may be critical in protecting the liver.

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Section: Discussionmentioning

confidence: 99%

Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway

Guo

Cui

et al. 2021

Mol Med Rep

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“…The higher ROS production can result in hepatocyte damage, and persistent accumulation of ROS leads to inflammation and release of TNF- α [100]. In HgCl 2 -induced liver injury, Hg 2+ gets tightly complexed with hydrosulphonyl moieties and depletes intracellular hydrosulphonyl moieties and leading to the generation of more ROS [86].…”

Section: Sirt1 Decreases the Inflammatory Responses In Dilimentioning

confidence: 99%

The Beneficial Roles of SIRT1 in Drug-Induced Liver Injury

Yan

Huang

Nisar

et al. 2019

Oxidative Medicine and Cellular Longevity

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Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF) as a result of accumulated drugs in the human body metabolized into toxic agents and helps generate heavy oxidative stress, inflammation, and apoptosis, which induces necrosis in hepatocytes and ultimately damages the liver. Sirtuin 1 (SIRT1) is said to have multiple vital roles in cell proliferation, aging, and antistress systems of the human body. The levels of SIRT1 and its activation precisely modulate its critical role in the interaction between multiple step procedures of DILI. The nuclear factor kappa-light-chain-enhancer of activated B cell- (NF-κB-) mediated inflammation signaling pathway, reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential collapse, and endoplasmic reticulum (ER) stress also contribute to aggravate DILI. Apoptosis is regarded as the terminal reaction followed by multiple signaling cascades including caspases, p53, and mitochondrial dysfunction which have been said to contribute in DILI. The SIRT1 activator is regarded as a potential candidate for DILI, because the former could inhibit signaling of p53, NF-κB, and ER stress. On the other hand, overexpression of SIRT1 also enhances the activation of antioxidant responses via Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor- (erythroid-derived 2-) like 2 (Nrf2) signaling. The current manuscript will highlight the mechanism of DILI and the interaction of SIRT1 with various cytoplasmic factors leading to DILI along with the summary of potent SIRT1 agonists.

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“…The TCA cycle is reported as the final common oxidation pathway of fat, carbohydrates, and amino acids, and is also the most important central pathway that connects almost all metabolic pathways of individuals [ 36 ]. In addition, the TCA cycle is closely related to some liver diseases.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

Sheng

Guo

et al. 2022

Molecules

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The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl4) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl4 (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl4-induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl4 was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl4-induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.

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Oxaloacetate Ameliorates Chemical Liver Injury via Oxidative Stress Reduction and Enhancement of Bioenergetic Fluxes

Cited by 25 publications

References 45 publications

Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway

Urantide prevents CCl4‑induced acute liver injury in rats by regulating the MAPK signalling pathway

The Beneficial Roles of SIRT1 in Drug-Induced Liver Injury

Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

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