Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis

Keegan, Andrew; Martini, Robert; Batey, Robert

doi:10.1016/0168-8278(95)80067-0

Cited by 75 publications

(51 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, no electron microscopic examination, no water and fat content measurement, and no MTR were available. Ethanol induced mitochondria damage and proliferation of SER in liver (29). Prolonged T 1water was reported by Hazle et al (8) and Ling and Brauer (30).…”

Section: Discussionmentioning

confidence: 58%

In vivo magnetic resonance (MR) study of fatty liver: Importance of intracellular ultrastructural alteration for MR tissue parameters change

Chai

Lin

Chen

et al. 2001

Magnetic Resonance Imaging

View full text Add to dashboard Cite

Fatty liver is thought to have a shorter T1 relaxation time than normal liver tissue, due to the accumulation of triglyceride. Previous studies regarding T1 and T2 relaxation times, however, show widely different results. In order to elucidate the mechanism responsible for the changes and diversity of relaxation times in fatty liver, we created two animal models in 14 rabbits, one acute form (N ‫؍‬ 6) and the other chronic form (N ‫؍‬ 8). Four rabbits were taken as a control group. Tissue relaxation times and the magnetization transfer (MT) effect of the liver tissue in these two models were measured. The results were correlated with biochemical analysis of water and fat content and histological examination, including findings in light microscopy and electron microscopy. Although the fatty ratio in both forms of fatty liver was similar, their tissue relaxation rate and MT effect were significantly different. The acute form showed prolongation of both T1 and T2 relaxation times (512 ؎ 51 msec vs. 710 ؎ 95 msec and 39 ؎ 1.8 msec vs. 48 ؎ 3.7 msec, respectively) and a decrease of the MT effect (50 ؎ 5.1% vs. 38 ؎ 6.3%), compared to those of the control group and preinduction liver. The chronic form showed shorter T1 and T2 values (526 ؎ 36 msec vs. 406 ؎ 56 msec and 36 ؎ 1.6 msec vs. 33 ؎ 2.3 msec, respectively) and a stronger MT effect (21 ؎ 0.9% vs. 26 ؎ 2.3%). In acute form fatty liver, electron microscopic examination revealed dramatic subcellular changes, such as vesicular transformation, a markedly increased amount of smooth endoplasmic reticulum (SER), and disruption of the crista. These changes were not found in the chronic form fatty liver. From this study, we concluded that the ultrastructural alteration in the subcellular organelles of hepatocyte might play a crucial role for the chameleonic presentation Index terms: fatty liver, MR; fatty liver, T1 relaxation time; fatty liver, T2 relaxation time; fatty liver, magnetization transfer effect; fatty liver; electron microscopy FATTY LIVER IS THE ACCUMULATION of triglycerides within hepatocytes. Fatty liver has been studied in vitro, on animal models, and in clinical cases with variable magnetic resonance (MR) methods, including conventional pulse sequences, chemical shift imaging, and MR spectroscopy. Although MR imaging (MRI) has higher sensitivity and specificity in tissue characterization than other imaging modalities, because of different relaxation times in normal and diseased tissues, in case of fatty liver, the MR diagnosis with conventional pulse sequences is not sensitive for detection of fatty deposition in the liver tissue (1,2). Chemical shift imaging works well in the assessment of the fatty amount in the liver by subtracting two sets of images, in-phase and out-phase images (3-7). MR spectroscopy, either by 1H or 13C techniques, successfully estimates fat content in the fatty liver (8 -14). The tissue relaxation changes of fatty liver have also been studied with various animal models. The results, however, were diverse (14 -21). The previous s...

show abstract

Section: Discussionmentioning

confidence: 58%

In vivo magnetic resonance (MR) study of fatty liver: Importance of intracellular ultrastructural alteration for MR tissue parameters change

Chai

Lin

Chen

et al. 2001

Magnetic Resonance Imaging

View full text Add to dashboard Cite

show abstract

“…An intake of 15 g ethanol/kg/d was achieved, as a result of which ethanol was estimated to account for 39% of total ingested kilojoules. As reported elsewhere (21), the serum ethanol concentration of the ethanol-consuming rats was regularly above 20 mM, and these blood levels were maintained throughout the day. After 16 wk on the diet, body weight in ethanol and pair-fed rats (group B, see below) was comparable, and histology showed that the livers of ethanol-fed rats developed steatosis without obvious inflammation, hepatocyte necrosis or fibrosis (21).…”

Section: Introductionmentioning

confidence: 80%

“…Animals in group A were fed commercial rat pellets (Allied Food, Sydney, Australia) and were induced to consume 40% ethanol in water, by introducing ethanol into the drinking water gradually, over 10 wk (21). An intake of 15 g ethanol/kg/d was achieved, as a result of which ethanol was estimated to account for 39% of total ingested kilojoules.…”

Section: Introductionmentioning

confidence: 99%

Chronic ethanol administration to rats decreases receptor-operated mobilization of intracellular ionic calcium in cultured hepatocytes and inhibits 1,4,5-inositol trisphosphate production: relevance to impaired liver regeneration.

Zhang¹,

Hornsfield²,

Farrell³

1996

J. Clin. Invest.

View full text Add to dashboard Cite

Ethanol, Liver Regeneration and [Ca] i transients. These changes were not due to an effect on the Ins(1,4,5) P 3 receptor on the endoplasmic reticulum or to a decrease in the size of the Ins(1,4,5) P 3 -mobilizable intracellular Ca 2 ϩ store. Further, mobilization of the same Ca 2 ϩ store by 2,5-di-tert -butylhydroquinone or thapsigargin restored the ability of hepatocytes from ethanol-fed rats to proliferate when exposed to EGF. It is concluded that chronic ethanol consumption inhibits liver regeneration by a mechanism that is, at least partly, the result of impaired receptor-operated [Ca 2 ϩ ] i signaling due to reduced generation of

show abstract

“…This could be indicative of more extensive damage previously observed in rats exposed to high doses of that substance. A higher dose of ethanol, (40 % v/v) results in steatosis, hepatitis, necrosis of hepatocytes and fibrosis, thus being suggested as an experimental model of the hepatic alcoholic disorder in Wistar rats (Keegan et al, 1995). Other authors who evaluated the toxicity of low doses of ethanol.…”

Section: Discussionmentioning

confidence: 99%

Ethanol in low chronic dose level attenuates major organic effects in malnourished rats

et al. 2009

View full text Add to dashboard Cite

The aim of the present study was to evaluate the chronic toxicity of ethanol low blood levels in malnourished rats. Female Wistar rats (220 g) were subjected to either an ad libitum diet (W, well-nourished, n=10) or food restriction (M, malnourished, n=10). Water (WW and MW) or ethanol solution (W5% and M5%) was offered to half of each nutritional group (n=5) as the only fluid source. The treatment was continued for two months. After sacrifice, blood biochemical parameters and macroscopic, histologic and morphometric evaluation of the liver were performed. Results indicated that: Ethanol consumption was higher in malnourished rats and minimized body weight loss in malnourished rats, while it decreased the body weight gain in well-nourished ones. Behavioral ethanol intoxication was more severe in malnourished rats. Malnutrition decreased hematocrit and hemoglobin but, on the other hand, ethanol was a protective factor of that effect (hemoglobin: MW 10.6 mg/dl / ME 13.02 mg/dl, p< 0.05). Ethanol increased the relative liver weight of both wellnourished and malnourished rats. Ethanol intake minimized iron pigment, collagen area and binuclear hepatocyte/ field increased by malnutrition. These data are in accordance with previous reports which showed ethanol as an important source of calories and, even chronically, ethanol still attenuates the effects of malnutrition.

show abstract

Ethanol-related liver injury in the rat: a model of steatosis, inflammation and pericentral fibrosis

Cited by 75 publications

References 19 publications

In vivo magnetic resonance (MR) study of fatty liver: Importance of intracellular ultrastructural alteration for MR tissue parameters change

In vivo magnetic resonance (MR) study of fatty liver: Importance of intracellular ultrastructural alteration for MR tissue parameters change

Chronic ethanol administration to rats decreases receptor-operated mobilization of intracellular ionic calcium in cultured hepatocytes and inhibits 1,4,5-inositol trisphosphate production: relevance to impaired liver regeneration.

Ethanol in low chronic dose level attenuates major organic effects in malnourished rats

Contact Info

Product

Resources

About