BACKGROUND: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. METHODS: Female Sprague Dawley(R) rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. RESULTS: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. CONCLUSIONS: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events.
BACKGROUND: Chronic ethanol consumption is associated with hepatic lipid peroxidation and the deposition or retention of aldehyde-adducted proteins postulated to be involved in alcohol-induced liver injury. The purpose of this study was to characterize hepatocellular formation of aldehyde-protein adducts during early stages of alcohol-induced liver injury. METHODS: Female Sprague Dawley(R) rats were subjected to the intragastric administration of a low-carbohydrate/high-fat total enteral nutrition diet or a total enteral nutrition diet containing ethanol for a period of 36 days. Indexes of hepatic responses to ethanol were evaluated in terms of changes in plasma alanine aminotransferase activity, hepatic histopathologic analysis, and induction of cytochrome P-4502E1 (CYP2E1). Immunohistochemical methods were used to detect hepatic proteins modified with malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE) for subsequent quantitative image analysis. RESULTS: After 36 days of treatment, rats receiving the alcohol-containing diet displayed hepatic histopathologies characterized by marked micro- and macrosteatosis associated with only minor inflammation and necrosis. Alcohol administration resulted in a 3-fold elevation of plasma alanine aminotransferase activity and 3-fold increases (p < 0.01) in hepatic CYP2E1 apoprotein and activity. Quantitative immunohistochemical analysis revealed significant (p < 0.01) 5-fold increases in MDA- and 4-HNE modified proteins in liver sections prepared from rats treated with alcohol. The MDA- or 4-HNE modified proteins were contained in hepatocytes displaying intact morphology and were colocalized primarily with microvesicular deposits of lipid. Aldehyde-modified proteins were not prevalent in parenchymal or nonparenchymal cells associated with foci of necrosis or inflammation. CONCLUSIONS: These results suggest that alcohol-induced lipid peroxidation is an early event during alcohol-mediated liver injury and may be a sensitizing event resulting in the production of bioactive aldehydes that have the potential to initiate or propagate ensuing proinflammatory or profibrogenic cellular events.
Authors: N Enomoto; K Ikejima; S Yamashina; A Enomoto; T Nishiura; T Nishimura; D A Brenner; P Schemmer; B U Bradford; C A Rivera; Z Zhong; R G Thurman Journal: Am J Physiol Gastrointest Liver Physiol Date: 2000-07 Impact factor: 4.052
Authors: H Kono; I Rusyn; M Yin; E Gäbele; S Yamashina; A Dikalova; M B Kadiiska; H D Connor; R P Mason; B H Segal; B U Bradford; S M Holland; R G Thurman Journal: J Clin Invest Date: 2000-10 Impact factor: 14.808
Authors: James J Galligan; Rebecca L Smathers; Kristofer S Fritz; L E Epperson; Lawrence E Hunter; Dennis R Petersen Journal: Chem Res Toxicol Date: 2012-05-01 Impact factor: 3.739
Authors: Martin J J Ronis; Angelica Butura; Brante P Sampey; Kartik Shankar; Ronald L Prior; Sohelia Korourian; Emanuele Albano; Magnus Ingelman-Sundberg; Dennis R Petersen; Thomas M Badger Journal: Free Radic Biol Med Date: 2005-09-01 Impact factor: 7.376
Authors: Sanjoy Roychowdhury; Megan R McMullen; Michele T Pritchard; Wei Li; Robert G Salomon; Laura E Nagy Journal: Free Radic Biol Med Date: 2009-07-17 Impact factor: 7.376
Authors: Rebecca L Smathers; James J Galligan; Colin T Shearn; Kristofer S Fritz; Kelly Mercer; Martin Ronis; David J Orlicky; Nicholas O Davidson; Dennis R Petersen Journal: J Lipid Res Date: 2013-01-28 Impact factor: 5.922
Authors: Vinood B Patel; Christina H Spencer; Tracey A Young; Mark O Lively; Carol C Cunningham Journal: Free Radic Biol Med Date: 2007-08-16 Impact factor: 7.376
Authors: Iraklis I Pipinos; Stanley A Swanson; Zhen Zhu; Aikaterini A Nella; Dustin J Weiss; Tanuja L Gutti; Rodney D McComb; B Timothy Baxter; Thomas G Lynch; George P Casale Journal: Am J Physiol Regul Integr Comp Physiol Date: 2008-05-14 Impact factor: 3.619