Analysis of islet beta cell functions and their correlations with liver dysfunction in patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)

Lu, Chunting; Yang, Jing; Huang, Shiyun; Feng, Lin; Li, Zejian

doi:10.1097/md.0000000000008638

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…The results of the present study demonstrated an increase in survival rates at doses of 20 and 40 mg/kg. ALT, AST, ALP and γ-GGT enzymes are released from liver cells into the serum when cell damage or necrosis occurs, with the levels of the enzymes reflecting the amount and type of liver damage ( 31 , 32 ). The biochemical index recorded in the present study suggested that liver function was severely damaged in the CCl 4 group.…”

Section: Discussionmentioning

confidence: 99%

Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

et al. 2018

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Liver fibrosis is a chronic disease that exhibits a complicated pathophysiology. It is characterized by the deposition of the extracellular matrix. Emodin, an active constituent isolated from rhubarb, has antibacterial, immunosuppressive and anti-inflammatory effects. In the present study, the mechanism through which emodin alleviates liver fibrosis in rats was investigated. A rat model of liver fibrosis was generated by administering CCl4 via subcutaneous injection twice a week for 12 weeks. Emodin or sodium carboxymethylcellulose (CMC), as the vehicle, were intragastrically administered daily. After 12 weeks, the liver function index was examined by blood analysis, histopathological scores of fibrosis was determined by hematoxylin and eosin staining and level of collagen deposition was examined by Masson staining. In addition, protein and RNA samples were collected for further analysis. The results of the present study revealed that emodin significantly reduced the liver function index and level of collagen deposition in a dose-dependent manner. Furthermore, emodin reduced the expression of transforming growth factor-β1 (TGF-β1) and the phosphorylation levels of mothers against decapentaplegic homolog 2/3, and inhibited the CCl4-induced downregulation of E-cadherin and upregulation of the mesenchymal markers, fibronectin and vimentin. The expression levels of TGF-β1, Snail family transcriptional repressor (Snail) 2, Snail, twist-related protein 1 and zinc finger E-box-binding homeobox (ZEB)1 and 2 mRNA were significantly decreased in emodin-treated groups compared with the untreated control. Collectively, the results of the present study suggested that emodin may exert antifibrotic effects via the suppression of TGF-β1 signaling and epithelial-mesenchymal transition.

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Section: Discussionmentioning

confidence: 99%

Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

et al. 2018

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“…To our understanding, this research is one of the few to assess the combined molecular effects of emodin and silymarin on the treatment of liver fibrosis. The combination of emodin and silymarin exerts a synergistic effect.When liver cells suffer damage or necrosis, the release of AST, ALT , -GGT, and AFP enzymes into the serum reveals the degree and type of liver injury based on the enzyme levels (Lu, Yang, Huang, Feng, & Li, 2017;Woo et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Biochemical study on Emodin and silymarin as a treatment for ccl4- induced hepatic fibrosis in mice.

Zein

Saad

Amer

2023

Bulletin of Faculty of Science, Zagazig University

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A natural supplement with potential for hepatoprotection, renowned due to the fact that it has anti-inflammatory, anti-fibrotic, and immunomodulating properties, is known as silymarin (Si) and emodin. We recently proved that early liver fibrosis can be stopped in its tracks by using the typical therapeutic doses of silymarin and emodin. We used CCl4 to cause liver damage in mice in order to further investigate the advantages of silymarin, emodin, and their combination administration upon liver modifications following the cessation of hepato-toxin. Carbon tetrachloride administration induces inflammation and liver fibrosis. Fifty Swiss albino mice were apportioned among 5 groups at random (n = 10). The negative control group received olive oil twice a week for 4 weeks. The positive control group(CCl4 group) received CCl4 in olive oil, by intraperitoneal injection, twice a week for four weeks. The emodin-treated group, after induction of fibrosis, was injected (i.p)with emodin daily for 3 weeks. After induction of fibrosis, the silymarin treated group received silymarin orally every day for 3 weeks. After induction of fibrosis, the combination treated group received Emodin ( i.p) and silymarin orally every day for 3 weeks. We evaluated indicators of hepatic stellate cell activation (alpha-SMA expression) and liver function tests 4 weeks after the experiment had started. The novel outcome of this study proposed that emodin ,silymarin and their combination could reduce liver inflammation. The effects of emodin mixed with silymarin were more efficient than those of emodin or silymarin alone.

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“…On the other hand, OPLS-DA showed that AST was a primarily contributed discrimination factor between the two groups. AST levels higher than ALT levels reflected more serious damage of liver cells ( Lu et al, 2017 ). In the “Clinical diagnosed Group,” the concentrations of total protein, amylase, and hemoglobin were lower than in the “Newborn-screen Group.” Hypoproteinemia and reduction of amylase activity also reflected advanced hepatic damage ( Donaldson et al, 1979 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency

Zhang

Zhu²,

Miao³

et al. 2022

Front. Mol. Biosci.

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Introduction: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a pan-ethnic complicated inborn error of metabolism but the specific mechanism is not fully understood.Methods: A total of 169 patients with NICCD who have biallelic pathogenic SLC25A13 variants detected by targeted next-generation sequencing were collected. They were divided into the “Newborn-screen Group” and “Clinical diagnosed Group” depending on the newborn screening results. Amino acid and acylcarnitine profiles were measured by MS/MS. The total bile acids, blood amino acids and acylcarnitines, general biochemistry, blood count, and coagulation parameters were monitored every 2–3 months. We compared the differences in metabolic indices and their dynamic changes between these two groups. The Mann–Whitney test and orthogonal partial least squares discrimination analysis (OPLS-DA) were used for statistical analysis.Results: At the onset of NICCD, we found that the “Clinical diagnosed Group” had higher levels of intermediate products of the urea cycle, free carnitine, and short-chain and long-chain acylcarnitines than those in the “Newborn-screen Group,” but the levels of ketogenic/glucogenic amino acids and several medium-chain acylcarnitines were lower. Furthermore, concentrations of direct bilirubin, total bile acid, lactate, prothrombin time, and several liver enzymes were significantly higher while total protein, amylase, and hemoglobin were lower in the “Clinical diagnosed Group” than in the “Newborn-screen Group.” Dynamic change analysis showed that direct bilirubin, albumin, arginine, and citrulline were the earliest metabolic derangements to reach peak levels in NICCD groups, followed by acylcarnitine profiles, and finally with the elevation of liver enzymes. All abnormal characteristic metabolic indicators in the “Newborn-screen Group” came back to normal levels at earlier ages than the “Clinical diagnosed Group.” c.852_855del (41.2%), IVS16ins3kb (17.6%), c.615 + 5G>A (9.6%), 1638_1660dup (4.4%), and c.1177 + 1G>A (3.7%) accounted for 76.5% of all the mutated SLC25A13 alleles in our population.Conclusion: Argininosuccinate synthesis, gluconeogenesis, ketogenesis, fatty acid oxidation, liver function, and cholestasis were more severely affected in the “Clinical diagnosed Group.” The “Newborn-screen Group” had a better prognosis which highlighted the importance of newborn screening of NICCD.

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Analysis of islet beta cell functions and their correlations with liver dysfunction in patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD)

Cited by 6 publications

References 34 publications

Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

Emodin alleviates CCl4‑induced liver fibrosis by suppressing epithelial‑mesenchymal transition and transforming growth factor‑β1 in rats

Biochemical study on Emodin and silymarin as a treatment for ccl4- induced hepatic fibrosis in mice.

Dynamic changes of metabolic characteristics in neonatal intrahepatic cholestasis caused by citrin deficiency

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