Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis

Guo, Chang; chen, Lizhu; Huang, Jie; Wang, Yuan-Fang; Shi, Changxuan; Gao, Jing; Hong, Yannv; Chen, Tong; Qiu, Longxin

doi:10.1016/j.cbi.2018.04.002

Cited by 10 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The functional role of aldo-keto reductases in cancer metabolism is not fully determined [96][97][98][99][100]. This reductase superfamily is associated with oxidative stress and inflammation initiated carcinogenesis [96].…”

Section: Discussionmentioning

confidence: 99%

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

View full text Add to dashboard Cite

The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10−12) and CLD compared to healthy controls (p = 4.1 × 10−7). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10−6) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10−6). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation.

show abstract

Section: Discussionmentioning

confidence: 99%

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Ismail

Fiehn

Elfert

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…同时, ALD-DILI患者体内牛磺石胆酸、(R)-乳酸、L-色氨酸均表现出一定程度的升高. 有研究显示, 乙醇可促进体内半乳糖代谢 [18] 和肝糖酵解, 可导致D-半乳糖代谢产物3-Ketolactose含量升高; 牛磺石胆酸(taurolithocholic acid, TLCA)是一种具有潜在肝毒性的次生胆汁盐 [19] , 可能通过直接作用于胆管膜而引起胆汁淤积, 从而损害胆管收缩和胆管分泌 [20,21] , 而血清牛磺石胆酸升高亦常见于肝硬化等终末期肝病 [22] ; 此外, 急性酒精中毒可导致大量乳酸堆积 [23] , 而乳酸升高与肝衰竭的发生具有一定相关性 [24] , 而色氨酸升高亦可一定程度导致肝性脑病的发生 [25] . 上述结果均表明, ALD-DILI患者具有一定ALD的代谢特征, 且部分代谢物的升高可能与许多严重的并发症相关, 这可能是本课题组前期临床观察中ALD-DILI患者治愈率更低的因素之一 [8] .…”

Section: 讨论unclassified

Metabolomic profiling and biomarkers of drug-induced liver injury with pre-existing alcoholic liver disease

Wang¹,

Jing²,

Niu³

et al. 2019

Sci. Sin.-Vitae

View full text Add to dashboard Cite

“…Thus, there is an increasing requirement for alternative and natural medicine to treat ALD. Recently, the aldose reductase (AR)/polyol pathway has been reported to be involved in the development of ALD, and treatment with AR inhibitor improves ALD in rodents [3–5]. This article reviews the biological effect of some potent AR inhibitors of plant origin on ALD, and the mechanisms by which AR inhibitors improve ALD.…”

Section: Introductionmentioning

confidence: 99%

Aldose Reductase Inhibitors of Plant Origin in the Prevention and Treatment of Alcoholic Liver Disease: A Minireview

Qiu

Guo

Hua

2019

BioMed Research International

Self Cite

View full text Add to dashboard Cite

Alcoholic liver disease (ALD) is caused by heavy alcohol consumption over a long period. Acetaldehyde-mediated toxicity, oxidative stress, and imbalance of lipid metabolism are generally considered involved in the initiation of ALD. There is an increasing requirement for alternative and natural medicine to treat ALD. Recently, aldose reductase (AR) has been reported to be involved in the development of ALD by affecting inflammatory cytokines, oxidative stress, and lipid metabolism. Here, we review the effect of plant-derived AR inhibitors on ALD in rodents. And we conclude that AR inhibitors of plant origin may enhance antioxidant capacity, inhibit lipid peroxidation and inflammatory cytokines expression, and activate AMP-activated protein kinase thereby subsequently suppressing alcohol-induced lipid synthesis in liver to achieve ALD protection. This review reveals that natural AR inhibitor may be potential therapeutic agent for ALD.

show abstract

Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis

Cited by 10 publications

References 36 publications

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues

Metabolomic profiling and biomarkers of drug-induced liver injury with pre-existing alcoholic liver disease

Aldose Reductase Inhibitors of Plant Origin in the Prevention and Treatment of Alcoholic Liver Disease: A Minireview

Contact Info

Product

Resources

About