FRIDAY, April 11 (HealthDay News) -- Deleting a gene involved in protecting cells against xenobiotic and oxidative stress leads to liver damage and death in mice fed an ethanol diet, researchers report in the April issue of Gastroenterology.
Jutta Lamle, from Medical School Hannover in Hannover, Germany, and colleagues generated mice lacking the transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2-/-) and fed them an ethanol diet.
The researchers found that mortality linked to liver failure was much higher in mice lacking Nrf2-/- than wild-type mice fed similar doses of ethanol. Ethanol feeding of these mice led to a reduced ability to detoxify acetaldehyde, marked steatosis in the liver, a gradual depletion of total and mitochondrial-reduced glutathione, pronounced structural and functional changes to mitochondria, and an aggravated inflammatory response mediated by Kupffer cells.
"Together these changes lead to a vicious cycle of accumulating hepatocellular damage, ultimately leading to liver failure and death of Nrf2-/- mice," Lamle and colleagues conclude. "Our data establish a central role for Nrf2-/- in the protection against ethanol-induced liver injury."
Abstract
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