TUNEL-positive hepatocytes in alcoholic liver disease

Zhao, Ming; Laissue, Jean A.; Zimmermann, Arthur

doi:10.1007/s004280050108

Cited by 38 publications

(5 citation statements)

References 40 publications

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“…DNA damage may be incurred due to exposure of the hepatocytes to ethanol intoxication-induced oxidative stress, causing the production of ROS and TNF-α-induced cell death, resulting in hepatic damage [26]. The current study showed that the ethanol intoxication of mouse hepatocytes increased the number of apoptotic cells observed with the TUNEL assay and phase-contrast microscopy, which is consistent with the literature using human alcoholic hepatitis specimens [42,43]. However, in the current study, when pre-treated with either Silymarin or BERM, a substantial decrease in the number of ethanol-induced apoptotic cells was noticed, confirming the in vivo hepatoprotective effect of BERM against alcohol intoxication.…”

Section: Discussionsupporting

confidence: 91%

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies

Jairaman¹,

Alehaideb

Yacoob³

et al. 2022

Metabolites

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The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication with the prediction of potential targets employing in silico studies. An oral administration of different concentrations (100, 200 and 400 mg/kg body weight) of BERM before high-dose ethanol via intraperitoneal injection was performed in mice. On day 7, liver sections were dissected for histopathological examination. The ethanol intoxication caused liver injury and large areas of necrosis. The pre-BERM administration decreased the ethanol-induced liver damage marker tumor necrosis factor-alpha (TNF-α) expression, reduced hepatotoxicity revealed by nuclear deoxyribonucleic acid (DNA) fragmentation and decreased oxidative stress indicated by malondialdehyde and glutathione contents. Our in silico studies have identified BERM-derived metabolites exhibiting the highest predicted antioxidant and free radical scavenger activities. Molecular docking studies showed that most of the metabolites were predicted to be enzyme inhibitors such as carbonic anhydrase inhibitors, which were reported to stimulate the antioxidant defense system. The metabolites predominantly presented acceptable pharmacokinetics and safety profiles, suggesting them as promising new antioxidant agents. Altogether, the BERM extract exerts antioxidative activities and shows promising hepatoprotective effects against ethanol intoxication. Identification of related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

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Section: Discussionsupporting

confidence: 91%

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies

Jairaman¹,

Alehaideb

Yacoob³

et al. 2022

Metabolites

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“…Although, SPARC like 1 is barely expressed in normal liver, significance of its overexpression in HCC is not well studied. Overexpression of tenascin C and type IV collagen induces a defective extracellular matrix pattern in hepatocellular cancer . Other major overexpressed proteins in HCC were vitronectin and fibronectin, which are involved in cell migration and adhesion in HCC along with other basement membrane proteins such as collagen IV and laminin. − …”

Section: Discussionmentioning

confidence: 99%

A Quantitative Proteomic Approach for Identification of Potential Biomarkers in Hepatocellular Carcinoma

et al. 2008

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. In this study, our objective was to identify differentially regulated proteins in HCC through a quantitative proteomic approach using iTRAQ. More than 600 proteins were quantitated of which 59 proteins were overexpressed and 92 proteins were underexpressed in HCC as compared to adjacent normal tissue. Several differentially expressed proteins were not implicated previously in HCC. A subset of these proteins (six each from upregulated and downregulated groups) was further validated using immunoblotting and immunohistochemical labeling. Some of the overexpressed proteins with no previous description in the context of HCC include fibroleukin, interferon induced 56 kDa protein, milk fat globule-EGF factor 8, and myeloidassociated differentiation marker. Interestingly, all the enzymes of urea metabolic pathway were dramatically downregulated. Immunohistochemical labeling confirmed differential expression of fibroleukin, myeloid associated differentiation marker and ornithine carbamoyl transferase in majority of HCC samples analyzed. Our results demonstrate quantitative proteomics as a robust discovery tool for the identification of differentially regulated proteins in cancers.

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“…Although it has been shown that chronic ethanol consumption increases apoptosis of hepatocytes in mice (Goldin et al, 1993;Deaciuc et al, 2001); rats (Benedetti et al, 1988;Kurose et al, 1997;Mi et al, 2000;Slomiany et al, 1999;Yacoub et al, 1995); minipigs (Halsted et al, 1996), and humans (Zhao et al, 1997), the numbers of apoptotic hepatocytes are small. Others (Rashid et al, 1999) have shown, and we have con®rmed here (Figure 2), that there is no signi®cant apoptosis in the liver of mice fed chronically with the DeCarli-Lieber ethanol containing liquid diet.…”

Section: Discussionmentioning

confidence: 99%

Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-xL proteins

et al. 2002

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Elevation of serum interleukin-6 (IL-6) levels is always associated with alcoholic liver disease (ALD), but the significance of such elevation is not clear. Here we show that chronic ethanol consumption induces significant apoptosis in the liver of IL-6 (-/-) mice but not IL-6 (+/+) mice. IL-6 (-/-) hepatocytes are more susceptible to ethanol- and tumor necrosis factor alpha- (TNFalpha-) induced apoptotic killing, which can be corrected by IL-6. Expression of both anti-apoptotic (such as Bcl-2 and Bcl-x(L)) and proapoptotic (such as Bax) proteins is markedly elevated in the liver of human ALD and chronically ethanol-fed IL-6 (+/+) mice. On the contrary, induction of Bcl-2 and Bcl-x(L) is not observed in the liver of chronically ethanol-fed IL-6 (-/-) mice, whereas expression of Bax protein remains elevated. Injection of IL-6 markedly induces expression of Bcl-2 and Bcl-x(L) but not Bax in the liver. Finally, high concentrations of ethanol inhibit IL-6-activated anti-apoptotic signal, but increasing the concentrations of IL-6 is able to overcome such inhibitory effect. These findings suggest that elevated serum IL-6 levels in ALD may overcome the inhibitory effect of ethanol on IL-6-mediated anti-apoptotic signals and prevent alcohol-induced hepatic apoptosis by induction of Bcl-2 and Bcl-x(L).

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TUNEL-positive hepatocytes in alcoholic liver disease

Cited by 38 publications

References 40 publications

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies

A Quantitative Proteomic Approach for Identification of Potential Biomarkers in Hepatocellular Carcinoma

Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-xL proteins

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