Aspirin can prevent liver damage that afflicts millions

[theblackalchemist]

Simple aspirin may prevent liver damage in millions of people suffering from side effects of common drugs, alcohol abuse, and obesity-related liver disease, a new Yale University study suggests.

 

The study in the January 26 edition of Journal of Clinical Investigation documents that in mice, aspirin reduced mortality caused by an overdose of acetaminophen, best known by the brand name Tylenol. It further showed that a class of molecules known as TLR antagonists, which block receptors known to activate inflammation, have a similar effect as aspirin. Since these agents seem to work by reducing injury-induced inflammation, the results suggest aspirin may help prevent and treat liver damage from a host of non-infectious causes, said Wajahat Mehal, M.D., of the Section of Digestive Diseases and Department of Immunobiology at Yale School of Medicine.

 

"Many agents such as drugs and alcohol cause liver damage, and we have found two ways to block a central pathway responsible for such liver injury," Mehal said. "Our strategy is to use aspirin on a daily basis to prevent liver injury, but if it occurs, to use TLR antagonists to treat it."

 

Promising drugs that have failed clinical trials because of liver toxicity might be resurrected if combined with aspirin, Mehal said.

 

"This offers the exciting possibility of reducing a lot of pain and suffering in patients with liver diseases, using a new and very practical approach," Mehal said.

 

 

Source: Yale University

[theblackalchemist]

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Aspirin counteracts new mechanisms of acetaminophen-induced liver damage

 

Overdoses of acetaminophen (also known as paracetamol) account for most drug overdoses in a number of countries, including the United States. Such overdoses damage the liver, causing acute liver failure, which can be fatal. Wajahat Mehal and colleagues, at Yale University, New Haven, have now provided new insight into the mechanisms by which acetaminophen causes liver damage in mice and determined that aspirin provides substantial protection from these toxic effects of acetaminophen.

 

Overdoses of acetaminophen cause two waves of liver damage. The first wave of liver cell destruction is a result of the toxic nature of acetaminophen. The second wave is mediated by molecules of the immune system, which is activated in response to the initial acetaminophen-induced liver damage. In the study, the first wave of dying mouse liver cells were found to promote the production of immune molecules known as proinflammatory cytokines by sinusoidal endothelial cells in the liver. This production of proinflammatory cytokines required two signaling pathways to be active, one initiated by the protein Tlr9 and one activated by a protein complex known as the Nalp3 inflammasome. Interestingly, aspirin was found to protect mice against acetaminophen-induced liver damage by downregulating proinflammatory cytokine production. In an accompanying commentary, Jacquelyn Maher, at the University of California, San Francisco, discusses the importance of these data for understanding the mechanisms underlying a severe clinical condition.

 

 

Source: Journal of Clinical Investigation