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. 2003 Jun;27(6):1015-22.
doi: 10.1097/01.ALC.0000071928.16732.26.

Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury

Brante P Sampey  1 , Soheila Korourian, Martin J Ronis, Thomas M Badger, Dennis R Petersen
Affiliations

Immunohistochemical characterization of hepatic malondialdehyde and 4-hydroxynonenal modified proteins during early stages of ethanol-induced liver injury

Brante P Sampey et al. Alcohol Clin Exp Res. 2003 Jun.

Abstract

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. VSports手机版.

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. V体育安卓版.

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 V体育ios版. 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. VSports最新版本.

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Figures

Fig. 1
Fig. 1
Photomicrographs of representative hematoxylin and eosin-stained liver sections prepared from an isocaloric-fed control rat (A) and a rat treated with ethanol for 36 days (B). A 40× magnification of the designated region reveals a foci of inflammatory cells by block arrows. Hepatocytes containing microsteatosis are designated with small arrows, whereas notched arrows designate macrosteatosis. Steatosis in the photomicrograph with 10× magnification (left) is concentrated in the periportal region.
Fig. 2
Fig. 2
Effects of chronic enteral ethanol administration on hepatic histopathology scores. Histopathologic assessment was performed as described in the text. Data are presented as mean ± SEM. *p < 0.05 compared with TEN controls.
Fig. 3
Fig. 3
Effect of chronic ethanol administration on CYP2E1 apoprotein and activity. Hepatic microsomes were isolated from TEN and ethanol-treated rats as described for determination of CYP2E1 apoprotein (A) expressed in arbitrary densitometric units (ADU) and activity (B). *p < 0.05 compared with TEN controls.
Fig. 4
Fig. 4
Immunohistochemical detection of MDA- and 4-HNE-modified proteins in liver sections prepared from TEN and ethanol-treated rats (magnification 10×). CV designates the central vein, whereas the periportal vein is identified by PP. Panels A and B are representative of MDA- or 4-HNE-stained sections from TEN control rats, respectively. Panels C (MDA) and D (4-HNE) are representative sections prepared from ethanol-treated rats. The enlarged areas of panels C and D show localization of immune-positive staining in hepatocytes characterized by normal morphology and microsteatosis. Quantitation of the immunostaining is presented in Table 2.
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