Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury

Liu, Hui; Li, Qian; Wáng, Ying; Hong, Huimin; Chen, Mengting; Wang, Yingyi; Hong, Fashui; Yang, Shu‐Long

doi:10.1111/hepr.12783

Cited by 10 publications

(3 citation statements)

References 27 publications

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“…Similar association between elevated NO concentrations and cellular apoptosis was described by others in several tissues including liver [ 22 ] and cardiovascular system [ 23 ].…”

Section: Resultssupporting

confidence: 84%

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

et al. 2017

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Estrogen-induced apoptosis has become a successful treatment for postmenopausal metastatic, estrogen receptor-positive breast cancer. Nitric oxide involvement in the response to this endocrine treatment and its influence upon estrogen receptor-positive breast cancer progression is still unclear.Nitric oxide impact on the MCF7 breast cancer line, before and after estrogen-induced apoptosis, was investigated in 3D culture systems using unique live-cell imaging methodologies.Spheroids were established from MCF7 cells vulnerable to estrogen-induced apoptosis, before and after exposure to estrogen.Spheroids derived from estrogen-treated cells exhibited extensive apoptosis levels with downregulation of estrogen receptor expression, low proliferation rate and reduced metabolic activity, unlike spheroids derived from non-treated cells. In addition to basic phenotypic differences, these two cell cluster types are diverse in their reactions to exogenous nitric oxide.A dual effect of nitric oxide was observed in the breast cancer phenotype sensitive to estrogen-induced apoptosis. Nitric oxide, at the nanomolar level, induced cell proliferation, high metabolic activity, downregulation of estrogen receptor and enhanced collective invasion, contributing to a more aggressive phenotype. Following hormone supplementation, breast cancer 3D clusters were rescued from estrogen-induced apoptosis by these low nitric oxide-donor concentrations, since nitric oxide attenuates cell death levels, upregulates survivin expression and increases metabolic activity.Higher nitric oxide concentrations (100nM) inhibited cell growth, metabolism and promoted apoptosis. These results suggest that nitric oxide, in nanomolar concentrations, may inhibit estrogen-induced apoptosis, playing a major role in hormonal therapy. Inhibiting nitric oxide activity may benefit breast cancer patients and ultimately reduce tumor recurrence.

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“…Similar association between elevated NO concentrations and cellular apoptosis was described by others in several tissues including liver [ 22 ] and cardiovascular system [ 23 ].…”

Section: Resultssupporting

confidence: 84%

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

et al. 2017

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“…Apoptosis is one of the most complex fate of a cell primarily depends on the balance between pro-apoptotic and anti-apoptotic proteins. Apoptosis occurs when this balance is compromised either by the up-regulation of pro-apoptotic proteins and/or down regulation of anti-apoptotic proteins (Hui et al, 2016). The results of our study reveal that TAA increased the expressions of pro-apoptotic proteins, such as Bad and Bax and decreased the expressions of anti-apoptotic proteins Bcl-2 and Bcl-xL.…”

Section: Resultsmentioning

confidence: 99%

Silymarin Protects Mouse Liver and Kidney from Thioacetamide Induced Toxicity by Scavenging Reactive Oxygen Species and Activating PI3K-Akt Pathway

et al. 2016

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Silymarin (SMN) has been shown to possess a wide range of biological and pharmacological effects. Besides, SMN has antioxidant and free radical scavenging activities. Thioacetamide (TAA) is a well-documented liver toxin that requires oxidative bioactivation to elicit its hepatotoxic effect which ultimately modifies amine-lipids and proteins. Our study has been designed in a TAA exposed mouse model to investigate whether SMN could protect TAA-induced oxidative stress mediated hepatic and renal damage. Results suggest that TAA generated reactive oxygen species (ROS), caused oxidative stress and induced apoptosis in the liver and kidney cells via JNK as well as PKC and MAPKs signaling. All these detrimental effects of TAA could, however, be suppressed by SMN which not only scavenged ROS but also induced PI3K-Akt cell survival pathway in the liver and prevented apoptotic pathways in both the organs. Histological studies, collagen staining and DNA fragmentation analysis also supported our results. Combining, we say that SMN possess beneficial role against TAA mediated hepatic and renal pathophysiology.

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“…In the liver, nitric oxide that is constitutively formed by the action of endothelial isoform of nitric oxide synthase (eNOS) maintains hepatic microcirculation and the integrity of endothelium. In contrast, the increased generation of nitric oxide by the inducible form of NOS (iNOS) due to the action of inflammatory cytokines contributes to hepatocyte apoptosis, liver tissue damage and fibrosis under such conditions as ischaemicreperfusion injury and also after exposure to CCl 4 [36,37]. Moreover nitric oxide synthase inhibitors were shown to prevent hepatic necrosis and to decrease the expression of tumour necrosis factor alpha (TNF-α) and cycloozygenase-2 in liver tissue of CCl 4 treated rats [38].…”

Section: Examination Of Cells From the Group Treated Withmentioning

confidence: 99%

The 5-HT1A Agonist Buspirone Decreases Liver Oxidative Stress and Exerts Protective Effect Against CCl4– Toxicity

Abdel-Salam¹,

Shaffie²,

Mohammed³

et al. 2017

JECT

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We aimed to study the effect of buspirone, an anxiolytic drug and 5-HT1A agonist on liver injury induced by carbon tetrachloride (CCl4) in rats. Rats were orally treated with CCl4 (2.8 mL/kg in olive oil) along with buspirone at 10, 20 or 30 mg/kg once daily starting with CCl4 and for one week thereafter. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as alkaline phosphatase (ALP) activities were determined in the serum. Markers of oxidative stress: lipid peroxidation (malondialdehyde; MDA), reduced glutathione (GSH), nitric oxide (nitrite/nitrate) levels were measured in the liver. Moreover, paraoxonase 1 activity was determined in the liver and serum. The administration of CCl4 led to significant increases in serum ALT, AST, and ALP activities. Results showed that there were significantly increased hepatic MDA, nitrite and decreased GSH levels. PON1 activity decreased both in the liver and serum, respectively. The immunohistochemical investigations using anti-caspase-3 antibody revealed that CCl4 caused apoptosis to many hepatocytes. DNA studies showed that CCl4 caused hypoploidy in hepatocytes. Rats treated with 20-30 mg/kg buspirone showed significant decrease in serum ALT and AST by 19.5-34.3% and 24.2-31.4%, respectively. Serum ALP decreased by 21.7% after 30 mg/kg buspirone. In the liver, the higher dose of the drug resulted in decreased MDA (by 15.8%), decreased nitric oxide (17.4%) and increased GSH (by 20.1%). Significantly increased serum PON1 activity by 43.9-53.5% was observed after treatment with 20-30 mg/kg buspirone. On histopathologic examination of liver sections, there was mild protective effect for the drug at 30 mg/kg. Sections stained with anti- caspase- 3 confirmed the results obtained from histopathological examination. Moreover, buspirone given at 30 mg/kg resulted in an increase in % of cells containing normal values of DNA. These results indicate that buspirone decreases liver oxidative stress and exerts protective effect against CCl4- toxicity. The study thus indicates more beneficial effects of buspirone as an anxiolytic drug and that the drug could be used safely in patients with liver disease.

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Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury

Cited by 10 publications

References 27 publications

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

Nitric oxide is cytoprotective to breast cancer spheroids vulnerable to estrogen-induced apoptosis

Silymarin Protects Mouse Liver and Kidney from Thioacetamide Induced Toxicity by Scavenging Reactive Oxygen Species and Activating PI3K-Akt Pathway

The 5-HT1A Agonist Buspirone Decreases Liver Oxidative Stress and Exerts Protective Effect Against CCl4– Toxicity

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