Cantharidin‐induced LO2 cell autophagy and apoptosis via endoplasmic reticulum stress pathway in vitro

Liu, Fang; Duan, Cancan; Zhang, Jianyong; Li, Xiaofei

doi:10.1002/jat.4022

Cited by 16 publications

(16 citation statements)

References 43 publications

(42 reference statements)

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“…To further evaluate the protective mechanism of ROF, human normal hepatocyte LO2 cells were cultured in vitro to observe whether ROF can improve hepatocyte apoptosis. LO2 cells were exposed to ETH (0, 50, 100, 200, 300, 400, 500, or 600 mm) to mimic the pathological features of alcohol-induced liver damage ( Shao et al, 2019 ; Liu F et al, 2020 ). When the ETH concentration was 200 mm, the cell activity decreased to about 60% ( Supplementary Figure S4 ).…”

Section: Resultsmentioning

confidence: 99%

Rhoifolin Alleviates Alcoholic Liver Disease In Vivo and In Vitro via Inhibition of the TLR4/NF-κB Signaling Pathway

et al. 2022

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Background: Alcoholic liver disease (ALD) is a common chronic liver disorder worldwide, which is detrimental to human health. A preliminary study showed that the total flavonoids within Citrus grandis “Tomentosa” exerted a remarkable effect on the treatment of experimental ALD. However, the active substances of Citrus grandis “Tomentosa” were not elucidated. Rhoifolin (ROF) is a flavonoid component present in high levels. Therefore, this research aimed to evaluate the hepatoprotective effects of ROF and its possible mechanisms.Methods: Molecular docking was performed to analyze the binding energy of ROF to the main target proteins related to ALD. Subsequently, mice were fed ethanol (ETH) for 49 days to establish the chronic alcoholic liver injury models. The liver pathological injury, serum aminotransferase levels, and oxidative stress levels in the liver tissue were measured. Human normal hepatocytes (LO2 cells) were incubated with ETH to construct the alcoholic liver cell model. The inflammatory markers and apoptosis factors were evaluated using real-time PCR and flow cytometry. Finally, the effects of ROF on the CYP2E1 and NF-κB signaling pathways were tested in vitro and in vivo.Results: Molecular docking results demonstrated that ROF was able to successfully dock with the target proteins associated with ALD. In animal studies, ROF attenuated ETH-induced liver damage in mice by decreasing the serum concentrations of AST and ALT, reducing the expression of inflammatory cytokines, and maintaining antioxidant balance in the liver tissue. The in vitro experiments demonstrated that ROF suppressed ETH-induced apoptosis in LO2 cells by promoting Bcl-2 mRNA and inhibiting Bax mRNA and caspase 3 protein expression. ROF decreased the level of LDH, ALT, AST, ROS, and MDA in the supernatant; induced the activity of GSH and SOD; and inhibited TNF-α, IL-6, and IL-1β expression levels. Mechanistically, ROF could significantly downregulate the expression levels of CYP2E1, TLR4, and NF-κB phosphorylation.Conclusion: This study indicates that ROF is the active component within the total flavonoids, which may alleviate ETH-induced liver injury by inhibiting NF-κB phosphorylation. Therefore, ROF may serve as a promising compound for treating ALD.

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Section: Resultsmentioning

confidence: 99%

Rhoifolin Alleviates Alcoholic Liver Disease In Vivo and In Vitro via Inhibition of the TLR4/NF-κB Signaling Pathway

et al. 2022

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“…According to reports in relevant studies, we used different concentrations of ethanol to treat LO2 cells to induce the pathogenesis of alcoholic liver injury as much as possible, meanwhile reduce interference factors such as high nutrition [22][23] . Ethanol administration resulted in a reduction of cell viability and ROF increases the viability of ethanol-treated LO2 cells (Fig.…”

Section: Rof Increases the Viability Of Ethanol-treated Lo2 Cellsmentioning

confidence: 99%

Rhoifolin Alleviate Alcoholic Liver Disease by Inhibiting the TLR4 / NF-kB Signaling Pathway and Attenuating Oxidative Stress

Mai¹,

Han²,

Zhong³

et al. 2021

Preprint

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Alcoholic liver disease (ALD) is caused by long-term excessive consumption of alcohol, which is affected by TLR4 / NF-kB mediated inflammatory response and CYP2E1-mediated oxidative stress effects. Rhoifolin (ROF) is a flavonoid compound in Citrus grandis ‘Tomentosa’, with antioxidant and anti-inflammation effect. However, the action of its effect on ALD has been elucidated yet. In the present study, we investigated ROF’s anti-inflammatory, antioxidant and antiapoptotic action in the treatment of ALD. In established ALD mice, ROF promoted hepatic function through downgrading the amount of aminotransferase, attenuating oxidative stress, and restoring antioxidant balance in hepatic tissue. Additionally, ROF significantly reduced the expression of inflammatory cytokines, such as NF-kB, TNF-a, IL-6, and IL-1b in the mice. In vitro experiments indicated that ROF increased the LO2 cells viability and inhibited cells apoptosis. ROF reversed the expression of CYP2E1, NLRP3, p-p65, p-IkB and TLR4, which were consistent with animal experiment. Overall, ROF can alleviate ethanol-induced liver injury through inhibiting oxidative stress and inflammation, and is a promising compound for ALD treatment.

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“…The results of Liu F et al 10 show that CTD‐induced liver toxicity of LO2 cells is mainly related to three pathways: cysteine and methionine metabolism; glutathione metabolism; and glycine, serine and threonine metabolism. The results of Liu F et al 11 show that CTD can induce LO2 cytotoxicity by inhibiting ERS and inducing autophagy and apoptosis. However, the detailed molecular mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 98%

Protective mechanism of Astragalus Polysaccharides against Cantharidin‐induced liver injury determined in vivo by liquid chromatography/mass spectrometry metabolomics

Huang

Tang

Chang

et al. 2021

Basic Clin Pharma Tox

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Cantharidin (CTD) is a promising anticancer drug; however, its dosage is limited by hepatotoxicity. We previously showed that Astragalus polysaccharides (APS) effectively improved chemical liver injury. In this study, we established a CTD‐induced subacute liver injury mouse model and examined the effects of APS on weight, liver indexes, histopathology, serum biochemical indexes and liver metabolism. Compared with the control group, mice in the CTD model group had obvious liver damage, which was partially prevented by APS. Metabolomics demonstrated that CTD caused liver damage mainly by regulating glycerophospholipid metabolism, ABC transporter pathways and choline metabolism in cancer in vivo. APS regulated primary bile acid biosynthesis and glycerophospholipid metabolism, thus decreasing the liver damage caused by CTD. This study revealed the protective mechanism of APS against CTD‐induced liver injury from the perspective of metabolomics. The results provide an important basis for analysing the mechanism of CTD‐induced liver toxicity and for assessing clinical treatment options to reduce CTD liver toxicity.

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Cantharidin‐induced LO2 cell autophagy and apoptosis via endoplasmic reticulum stress pathway in vitro

Cited by 16 publications

References 43 publications

Rhoifolin Alleviates Alcoholic Liver Disease In Vivo and In Vitro via Inhibition of the TLR4/NF-κB Signaling Pathway

Rhoifolin Alleviates Alcoholic Liver Disease In Vivo and In Vitro via Inhibition of the TLR4/NF-κB Signaling Pathway

Rhoifolin Alleviate Alcoholic Liver Disease by Inhibiting the TLR4 / NF-kB Signaling Pathway and Attenuating Oxidative Stress

Protective mechanism of Astragalus Polysaccharides against Cantharidin‐induced liver injury determined in vivo by liquid chromatography/mass spectrometry metabolomics

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