scholarly journals Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Davide Degli Esposti ◽  
Jocelyne Hamelin ◽  
Nelly Bosselut ◽  
Raphaël Saffroy ◽  
Mylène Sebagh ◽  
...  

The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts.

2018 ◽  
Vol 2 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Gayatri D Shirolkar ◽  
Sara Pasic ◽  
Jully Gogoi-Tiwari ◽  
Manoj K Bhat ◽  
John K Olynyk ◽  
...  

Chronic liver diseases (CLDs) are increasing in prevalence and their end-stage complications, namely, cirrhosis, liver failure and hepatocellular carcinoma represent major global challenges. The most common initiators of progressive CLD are viral hepatitis and long-term alcohol abuse as well as steatosis and steatohepatitis. Irrespective of the underlying aetiology, a common feature of CLD is the formation of hepatic ductular reactions, involving the proliferation of liver progenitor cells (LPCs) and their signalling to fibrosis-driving hepatic stellate cells. The Wnt/?-catenin pathway has been found to regulate development, stemness and differentiation, and alterations in its activity have been associated with tumour development. Recent data highlight the role of Wnt/?-catenin signalling in hepatic metabolism, steatosis and cancer, and suggest targeting of this pathway as a promising molecular strategy to potentially inhibit CLD progression and hepatocarcinogenesis.


2019 ◽  
Vol 20 (8) ◽  
pp. 817-822 ◽  
Author(s):  
Yu-Jen Tseng ◽  
Ling Dong ◽  
Yu-Feng Liu ◽  
Nuo Xu ◽  
Wei Ma ◽  
...  

Autophagy entails the removal of dysfunctional components to maintain cellular homeostasis. Over the years, studies of autophagy demonstrated its complex physiological and pathological roles in the liver. Apart from regulation of normal metabolic functions such as glycogenolysis, glycogenesis, and β-oxidation, autophagy also contributes to the modulation of various liver diseases. In this review, we provide a concise overview of the role of autophagy in regulating hepatic metabolism in healthy conditions and various chronic liver diseases. A well-rounded understanding of the role of autophagy may provide insight for future medical advancements in the field of hepatology.


Author(s):  
Carolina Armengol ◽  
Ramon Bartoli ◽  
Lucia Sanjurjo ◽  
Isabel Serra ◽  
Nuria Amezaga ◽  
...  

2020 ◽  
Vol 22 (1) ◽  
pp. 199
Author(s):  
Na Young Lee ◽  
Ki Tae Suk

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.


Author(s):  
Devaraj Ezhilarasan ◽  
Shanmugam Rajeshkumar ◽  
Thangavelu Lakshmi

2016 ◽  
Vol 311 (4) ◽  
pp. G667-G674 ◽  
Author(s):  
Natalie J. Torok

Reactive oxygen species are implicated in physiological signaling and cell fate decisions. In chronic liver diseases persistent and increased production of oxidative radicals drives a fibrogenic response that is a common feature of disease progression. Despite our understanding the biology of the main prooxidant enzymes, their targets, and antioxidant mechanisms in the liver, there is still lack of knowledge concerning their precise role in the pathogenesis of fibrosis. This review will examine the role of physiological redox signaling in the liver, provide an overview on recent advances in prooxidant and antioxidant pathways that are dysregulated during fibrosis, and highlight possible novel treatment targets.


2021 ◽  
Vol 12 ◽  
Author(s):  
Vishakha Singh ◽  
Amit Khurana ◽  
Prince Allawadhi ◽  
Anil Kumar Banothu ◽  
Kala Kumar Bharani ◽  
...  

Programmed cell death protein 1 (PD-1)/PD-ligand (L)1, the immune checkpoint inhibitors have emerged as a promising strategy for the treatment of various diseases including chronic liver diseases (CLDs) such as hepatitis, liver injury and hepatocellular carcinoma (HCC). The role of PD-1/PD-L1 has been widely inspected in the treatment of viral hepatitis and HCC. PD-1 is known to play a crucial role in inhibiting immunological responses and stimulates self-tolerance by regulating the T-cell activity. Further, it promotes apoptosis of antigen-specific T-cells while preventing apoptosis of Treg cells. PD-L1 is a trans-membrane protein which is recognized as a co-inhibitory factor of immunological responses. Both, PD-1 and PD-L1 function together to downregulate the proliferation of PD-1 positive cells, suppress the expression of cytokines and stimulate apoptosis. Owing to the importance of PD-1/PD-L1 signaling, this review aims to summarize the potential of PD-1/PD-L1 inhibitors in CLDs along with toxicities associated with them. We have enlisted some of the important roles of PD-1/PD-L1 in CLDs, the clinically approved products and the pipelines of drugs under clinical evaluation.


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