Activated hepatic stellate cells (HSCs) and myofibroblasts are the main producers of extracellular matrix (ECM) proteins that form the fibrotic tissue that leads to hepatic fibrosis. Reactive oxygen ...species (ROS) can directly activate HSCs or induce inflammation or programmed cell death, especially pyroptosis, in hepatocytes, which in turn activates HSCs and fibroblasts to produce ECM proteins. Therefore, antioxidants and the nuclear factor E2-related factor-2 signaling pathway play critical roles in modulating the profibrogenic response. The master proinflammatory factors nuclear factor-κB (NF-κB) and the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome may coordinate to produce and activate profibrogenic molecules such as interleukins 1β and 18, which effectively activate HSCs, to produce large amounts of fibrotic proteins. Furthermore, the NLRP3 inflammasome activates pro-caspase 1, which is upregulated by NF-κB, to produce caspase 1, which induces pyroptosis via gasdermin and the activation of HSCs. ROS play central roles in the activation of the NF-κB and NLRP3 signaling pathways via IκB (an inhibitor of NF-κB) and thioredoxin-interacting protein, respectively, thereby linking the molecular mechanisms of oxidative stress, inflammation and fibrosis. Elucidating these molecular pathways may pave the way for the development of therapeutic tools to interfere with specific targets.
Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and ...inflammation that lead to the excessive production of extracellular matrix (ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor (TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells (HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase (MAPK), toll-like receptor (TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease (NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor (VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.
Fructose and the Liver Muriel, Pablo; López-Sánchez, Pedro; Ramos-Tovar, Erika
International journal of molecular sciences,
06/2021, Letnik:
22, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Chronic diseases represent a major challenge in world health. Metabolic syndrome is a constellation of disturbances affecting several organs, and it has been proposed to be a liver-centered ...condition. Fructose overconsumption may result in insulin resistance, oxidative stress, inflammation, elevated uric acid levels, increased blood pressure, and increased triglyceride concentrations in both the blood and liver. Non-alcoholic fatty liver disease (NAFLD) is a term widely used to describe excessive fatty infiltration in the liver in the absence of alcohol, autoimmune disorders, or viral hepatitis; it is attributed to obesity, high sugar and fat consumption, and sedentarism. If untreated, NAFLD can progress to nonalcoholic steatohepatitis (NASH), characterized by inflammation and mild fibrosis in addition to fat infiltration and, eventually, advanced scar tissue deposition, cirrhosis, and finally liver cancer, which constitutes the culmination of the disease. Notably, fructose is recognized as a major mediator of NAFLD, as a significant correlation between fructose intake and the degree of inflammation and fibrosis has been found in preclinical and clinical studies. Moreover, fructose is a risk factor for liver cancer development. Interestingly, fructose induces a number of proinflammatory, fibrogenic, and oncogenic signaling pathways that explain its deleterious effects in the body, especially in the liver.
AbstractOxidative stress is importantly involved in the pathophysiology of various liver diseases. The redox state participates on the course of the inflammatory, metabolic and proliferative liver ...diseases. The main sources of the reactive oxygen species (ROS) are represented by the mitochondria and cytochrome P450 enzymes in the hepatocyte, Kupffer cells and neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. Hepatocyte’s proteins, lipids and DNA are among the cellular structures to be affected primarily by ROS and reactive nitrogen species (RNS). This process disrupts at cellular and molecular level the structure-function relationship on liver cells at different sites. Therefore, further studies on the molecular mechanisms of the oxidative stress pathways on liver diseases are urgently required, because they could explain the pathogenesis of various liver disorders. Moreover, new methods to evaluate oxidative stress like the oxidative markers among hepatocytes offers the potential to diagnose the degree of liver injury and ultimately to assess the response to pharmacological therapies. In this review, we discuss the molecular, metabolic and aging aspects of the oxidative stress, and the methods to evaluate oxidative stress on liver damage.
Since 1900 bc, several therapeutic activities have been attributed to the rhizomes of the plant Curcuma longa for a variety of diseases, including liver disorders. Curcumin, the main active compound ...obtained from this plant, was first isolated two centuries ago and its structure as diferuloylmethane was determined in 1910. Curcumin has shown anti‐inflammatory, anti‐oxidant, antifungal, antibacterial and anticancer activities. The pharmacological properties of curcumin were reviewed recently and focused mainly on its anticancer properties. However, its beneficial activity on liver diseases (known centuries ago, and demonstrated recently utilizing animal models) has not being reviewed in depth until now. The curcumin ability to inhibit several factors like nuclear factor‐κB, which modulates several pro‐inflammatory and profibrotic cytokines as well as its anti‐oxidant properties, provide a rational molecular basis to use it in hepatic disorders. Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl4) intoxication; moreover, it reverses CCl4 cirrhosis to some extent. Unfortunately, the number of studies of curcumin on liver diseases is still very low and investigations in this area must be encouraged because hepatic disorders constitute one of the main causes of worldwide mortality.
Background
Although included in some guidelines, the recommendation of interval colonoscopy after an acute diverticulitis (AD) episode has recently been questioned. In this study, we evaluated the ...incidence of colon cancer during the follow-up of an episode of AD.
Methods
A retrospective review was carried out of patients with conservatively treated AD at our Institution (January 2011 to December 2018) with or without endoscopic study. Patients who had no colonoscopy performed were followed for two years. The demographic, clinical, radiological, follow-up and anatomopathological records were analysed. We determined CT scan validity for the differential diagnosis of CC and AD; sensibility, specificity, predictive values and likelihood ratios were calculated. Patients lost to follow-up and patients who had had colonoscopy in the previous three years were excluded.
Results
This study included 285 patients with a mean age of 59 years. A total of 225 interval colonoscopies were performed and 60 patients without colonoscopy were followed up. There were 19 CC (6.7%) diagnosed, 14 with interval colonoscopy and 5 during follow-up; 8 (42.1%) happened in patients who had had an episode of uncomplicated AD. Although CT scan accuracy is high, 87.7%, positive and negative likelihood ratios were low, 4.67 and 0.64, respectively.
Conclusions
Interval colonoscopy should still be advisable after an episode of AD. The rationale for this statement is based on a non-negligible rate of hidden CC and an important uncertainty in the differential diagnosis.
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