Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis

Savari, Feryal; Badavi, Mohammad; Rezaie, Annahita; Gharib-Naseri, Mohammad Kazem; Mard, Seyyed Ali

doi:10.1080/10715762.2019.1608982

Cited by 10 publications

(10 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, ROS can also enhance the nuclear factor kappa B (NF- κ B), a transcription factor involved in the inflammatory process to induce proinflammatory cytokine production, and lycopene is well known to suppress the NF- κ B signaling pathway [ 15 , 52 ]. Our results are supported by other studies that did observe an increase of the pro- and anti-inflammatory cytokines in the liver parenchyma of different CS exposure models [ 24 , 53 ]. We believe that the increase in the IL-10 levels is probably a balance response to protect the host against the damage caused by the release of proinflammatory cytokines.…”

Section: Discussionsupporting

confidence: 92%

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke

Rocha

Machado-Junior

Souza

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

Cigarette smoke (CS) is the major cause of preventable death worldwide, and it can also cause damage to extrapulmonary organs, such as the liver, mainly due the generation of reactive oxygen species (ROS). The liver is an essential organ for human survival since it is mainly responsible for the body metabolism and among other things and it is the place where many endogenous and exogenous substances undergo biological transformation. Lycopene is a nonprovitamin A carotenoid found in red fruits and vegetables, and its role as a potent antioxidant is well known. In this study, we hypothesized that lycopene could protect mouse liver against long-term CS exposure. Thirty C57BL/6 mice were exposed to twelve cigarette smoke (12 cigarettes per day) for 60 days and pretreated with 25 mg/kg/day or 50 mg/kg/day of lycopene via orogastric gavage. After euthanasia, the hepatic tissue was collected for histopathological, antioxidant defense, oxidative stress, inflammatory, and collagen deposition analysis. Our analysis demonstrated that lycopene results in a suitable outcome to ameliorate the pathological changes, inflammatory and antioxidant profile in a mouse model of long-term CS exposure, and collagen accumulation in the hepatic extracellular matrix. This study demonstrates for the first time that supplementation of lycopene can be a possible pharmacological tool for the treatment of hepatic damage caused by exposure to long-term CS.

show abstract

Section: Discussionsupporting

confidence: 92%

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke

Rocha

Machado-Junior

Souza

et al. 2021

BioMed Research International

View full text Add to dashboard Cite

show abstract

“… 154 Fas ligand/Fas (CD95, APO-1) Human Fas expression is enhanced in NASH patients. 8 , 155 Human hepatocytes HepG2 hepatocytes treated with a mixture of OA/PA showed upregulated Fas expression and increased sensitivity to Fas-mediated apoptosis. 156 Mouse Liver-specific Fas overexpression compromises FAO and mitochondrial respiration, promoting lipid accumulation and insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

“… 157 Pharmacological or genetic Fas depletion in the liver protects mice from hepatic steatosis and insulin resistance in NASH mice models. 155 , 157 Mouse and Human In normal liver, the hepatocyte growth factor receptor Met binds to Fas, preventing its activation, whereas in both human and experimental NAFLD Fas sequestration by Met is abrogated, favouring the formation of Fas-Fas ligand complexes, and eventually inducing apoptosis. 158 …”

Section: Introductionmentioning

confidence: 99%

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

et al. 2020

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD stages range from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis and hepatocellular carcinoma. One of the crucial events clearly involved in NAFLD progression is the lipotoxicity resulting from an excessive fatty acid (FFA) influx to hepatocytes. Hepatic lipotoxicity occurs when the capacity of the hepatocyte to manage and export FFAs as triglycerides (TGs) is overwhelmed. This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation. In addition, we highlight the role of CD36/FAT fatty acid translocase in NAFLD pathogenesis. Up-to-date, it is well known that CD36 increases FFA uptake and, in the liver, it drives hepatosteatosis onset and might contribute to its progression to NASH. Clinical studies have reinforced the significance of CD36 by showing increased content in the liver of NAFLD patients. Interestingly, circulating levels of a soluble form of CD36 (sCD36) are abnormally elevated in NAFLD patients and positively correlate with the histological grade of hepatic steatosis. In fact, the induction of CD36 translocation to the plasma membrane of the hepatocytes may be a determining factor in the physiopathology of hepatic steatosis in NAFLD patients. Given all these data, targeting the fatty acid translocase CD36 or some of its functional regulators may be a promising therapeutic approach for the prevention and treatment of NAFLD.

show abstract

“…In particular, CS exposure activates the MAPK pathway in the lung [58], consistent with our findings. CS exposure also induces the overexpression of other inflammatory signaling pathways such as nuclear factor kappa B (NF-κB) and TNF-α [59]. It also reduces the expression of AhR protein in lung, decreasing the protective capacity of AhR against inflammatory and oxidative damages in lung [60].…”

mentioning

confidence: 99%

“…Oxidative Medicine and Cellular Longevity mice models show that chronic CS exposure activates the MAPK and NF-κB signaling pathways and induces the release of proinflammatory cytokines in the liver [59,61]. Activated MAPK pathway inhibits expression of CYP450-related genes affecting drug metabolism and detoxification in the hepatocytes [62].…”

mentioning

confidence: 99%

Eurotium cristatum Fermented Loose Dark Tea Ameliorates Cigarette Smoke‐Induced Lung Injury by MAPK Pathway and Enhances Hepatic Metabolic Detoxification by PXR/AhR Pathway in Mice

Huang

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1β in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.

show abstract

Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis

Cited by 10 publications

References 44 publications

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke

Lycopene Ameliorates Liver Inflammation and Redox Status in Mice Exposed to Long-Term Cigarette Smoke

Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

Eurotium cristatum Fermented Loose Dark Tea Ameliorates Cigarette Smoke‐Induced Lung Injury by MAPK Pathway and Enhances Hepatic Metabolic Detoxification by PXR/AhR Pathway in Mice

Contact Info

Product

Resources

About