Liver transplants: here's how omega-3s protect against inflammation

Fish oil protects liver from inflammation caused by transplants and other surgeries

Unraveled are the molecular mechanisms activated by Omega 3s to protect the liver from inflammation caused by surgeries, including transplants. They were discovered by a group of researchers from the University of Chile in Santiago in a study published in the journal PloS One. The discovery opens new perspectives in preventing ischemia-reperfusion damage, a phenomenon often associated with some operations.

The protective role of omega-3s in liver transplantation

Ischemia is a situation in which the flow of blood to an organ decreases or, even, is nullified. This phenomenon, associated with events such as heart attack or certain surgeries, results in a tissue-damaging oxygen deficiency. On the other hand, reperfusion, i.e., the restoration of blood circulation, can also damage organs, especially because of the strong inflammation triggered by the activation of the immune system. In particular, ischemia-reperfusion damage seriously endangers tissue health after some surgeries in which these two phenomena occur. A much-studied case is that of liver transplants, where it has been shown that this type of damage can be limited through appropriate treatments of the organ to be transplanted. Experiments have, for example, shown that in rats the intake of the Omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) protects the donor liver from damage. The effectiveness of these fatty acids is based on reducing the activation of NF-kB, an inflammation-associated protein that is activated by this type of damage.

New details on mechanisms of action

The South American researchers uncovered further details of this process by analyzing the activity of NF-kB and other related molecules in rats that were given a fish oil supplement for 7 days prior to inducing ischemia-reperfusion damage to the liver. After this first week, liver damage was induced with 1 hour of ischemia followed by 20 hours of reperfusion. Regarding general liver health status, Omega-3 intake was associated with normalization of transaminase levels and liver morphology, parameters altered in liver damage. Molecular analyses have, moreover, revealed that in addition to reducing NF-kB activation, these fatty acids promote the association between NF-kB and a molecule with anti-inflammatory action, PPAR-α. At the same time, the researchers found that Omega-3 treatment increases the stability of IκB-α, a molecule that counteracts NF-kB activation. The result of these phenomena is an increase in the expression of PPAR-α-regulated genes and a normalization of the levels of IL-lβ and TNF-α, two pro-inflammatory molecules whose production is controlled by NF-kB.

Omega-3, an efficacy with no more secrets

Taken together, these data indicate that PPAR-α and NF-κB compete to control the production of inflammation mediators. Omega-3 fatty acids, therefore, would protect the liver from ischemia-reperfusion injury by promoting the formation of complexes between PPAR-α and NF-κB and increasing the stability of IκB-α.  

Source 

1. Zúñiga J, Cancino M, Medina F, Varela P, Vargas R, Tapia G, Videla LA, Fernández V, "N-3 PUFA supplementation triggers PPAR-α activation and PPAR-α/NF-κB interaction: anti-inflammatory implications in liver ischemia-reperfusion injury," PLoS One. 2011;6(12):e28502. Epub 2011 Dec 8