Name: the dimethylnitrosamine induced liver fibrosis model in the rat
Uploaded: 2016-06-17T14:15:00
Description: Watch this Scientific Journal Video about The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat at JoVE.com

The authors acknowledge the funding support from the Ministry of Education, Singapore, grant number MOE2010-IF-1-025.

All animal experiments were approved by the animal care and use committee of the School of Applied Science, Temasek Polytechnic.
1. Preparation of DMN
<ol>
	<li>Pipette 200 &#181;l of DMN (1 g/ml stock solution) and add 19.8 ml of PBS to prepare 10 mg/ml DMN solution for the injection. 
	Note: DMN is carcinogenic. Use a fume hood to prepare the DMN and perform the animal injections.</li>
</ol>
2. Intraperitoneal Injection of DMN
<ol>
	<li>Use male Wistar rats with an average weight...

<ol>
	<li>Magee, P. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toxic+liver+injury;+the+metabolism+of+dimethylnitrosamine.">Toxic liver injury; the metabolism of dimethylnitrosamine.</a> Biochem J. 64 (4), 676-682 (1956).</li><li>Pritchard, D. J., Butler, W. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Apoptosis-the+mechanism+of+cell+death+in+dimethylnitrosamine-induced+hepatotoxicity.">Apoptosis-the mechanism of cell death in dimethylnitrosamine-induced hepatotoxicity.</a> J Pathol. 158 (3), 253-260 (1989).</li><li>Madden, J. W., Gertman, P. M., Peacock, E. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dimethylnitrosamine-induced+hepatic+cirrhosis:+a+new+canine+model+of+an+ancient+human+disease.">Dimethylnitrosamine-induced hepatic cirrhosis: a new canine model of an ancient human disease.</a> Surgery. 68 (1), 260-267 (1970).</li><li>Jenkins, S. A., Grandison, A., Baxter, J. N., Day, D. W., Taylor, I., Shields, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+dimethylnitrosamine-induced+model+of+cirrhosis+and+portal+hypertension+in+the+rat.">A dimethylnitrosamine-induced model of cirrhosis and portal hypertension in the rat.</a> J Hepatol. 1 (5), 489-499 (1985).</li><li>J&#233;z&#233;quel, A. M., Mancini, R., Rinaldesi, M. L., Macarri, G., Venturini, C., Orlandi, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+morphological+study+of+the+early+stages+of+hepatic+fibrosis+induced+by+low+doses+of+dimethylnitrosamine+in+the+rat.">A morphological study of the early stages of hepatic fibrosis induced by low doses of dimethylnitrosamine in the rat.</a> J Hepatol. 5 (2), 174-181 (1987).</li><li>George, J., Chandrakasan, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+characteristics+of+dimethylnitrosamine+induced+fibrotic+liver+collagen.">Molecular characteristics of dimethylnitrosamine induced fibrotic liver collagen.</a> Biochim Biophys Acta, Protein Struct Mol Enzymol. 1292 (2), 215-222 (1996).</li><li>Winwood, P. J., Arthur, M. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kupffer+cells:+their+activation+and+role+in+animal+models+of+liver+injury+and+human+liver+disease.">Kupffer cells: their activation and role in animal models of liver injury and human liver disease.</a> Semin Liver Dis. 13 (1), 50-59 (1993).</li><li>Nakamura, T., Sakata, R., Ueno, T., Sata, M., Ueno, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhibition+of+transforming+growth+factor&#946;+prevents+progression+of+liver+fibrosis+and+enhances+hepatocyte+regeneration+in+dimethylnitrosamine-treated+rats.">Inhibition of transforming growth factor&#946; prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats.</a> Hepatology. 32 (2), 247-255 (2000).</li><li>Shek, F. W., Benyon, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+can+transforming+growth+factor+beta+be+targeted+usefully+to+combat+liver+fibrosis?.">How can transforming growth factor beta be targeted usefully to combat liver fibrosis?.</a> Eur J Gastroenterol Hepatol. 16 (2), 123-126 (2004).</li><li>Wang, J. H., Shin, J. W., Son, J. Y., Cho, J. H., Son, C. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antifibrotic+effects+of+CGX,+a+traditional+herbal+formula,+and+its+mechanisms+in+rats.">Antifibrotic effects of CGX, a traditional herbal formula, and its mechanisms in rats.</a> J Ethnopharmacol. 127 (2), 534-542 (2010).</li><li>Su, L. J., Hsu, S. L., Yang, J. S., Tseng, H. H., Huang, S. F., Huang, C. Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+gene+expression+profiling+of+dimethylnitrosamine-induced+liver+fibrosis:+from+pathological+and+biochemical+data+to+microarray+analysis.">Global gene expression profiling of dimethylnitrosamine-induced liver fibrosis: from pathological and biochemical data to microarray analysis.</a> Gene Expr. 13 (2), 107-132 (2006).</li><li>M&#252;ller, A., Machnik, F., Zimmermann, T., Schubert, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thioacetamide-induced+cirrhosis-like+liver+lesions+in+rats+usefulness+and+reliability+of+this+animal+model.">Thioacetamide-induced cirrhosis-like liver lesions in rats usefulness and reliability of this animal model.</a> Exp Pathol. 34 (4), 229-236 (1988).</li><li>Martinez-Hernandez, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+hepatic+extracellular+matrix.+II.+Electron+immunohistochemical+studies+in+rats+with+CCl4-induced+cirrhosis.">The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis.</a> Lab Invest. 53 (2), 166-186 (1985).</li><li>Pritchard, M. T., Apte, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Models+to+Study+Liver+Regeneration.">Models to Study Liver Regeneration.</a> Liver Regeneration. , 15-40 (2015).</li><li>Kountouras, J., Billing, B. H., Scheuer, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prolonged+bile+duct+obstruction:+a+new+experimental+model+for+cirrhosis+in+the+rat.">Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat.</a> Br J Exp Pathol. 65 (3), 305-311 (1984).</li><li>Marques, T. G., Chaib, E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Review+of+experimental+models+for+inducing+hepatic+cirrhosis+by+bile+duct+ligation+and+carbon+tetrachloride+injection.">Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection.</a> Acta Cir Bras. 27 (8), 589-594 (2012).</li><li>Wasser, S., Tan, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Experimental+models+of+hepatic+fibrosis+in+the+rat.">Experimental models of hepatic fibrosis in the rat.</a> Ann Acad Med Singapore. 28 (1), 109-111 (1999).</li><li>George, J., Chandrakasan, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Biochemical+abnormalities+during+the+progression+of+hepatic+fibrosis+induced+by+dimethylnitrosamine.">Biochemical abnormalities during the progression of hepatic fibrosis induced by dimethylnitrosamine.</a> Clin Biochem. 33 (7), 563-570 (2000).</li><li>Shimizu, I., Ma, Y. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+Sho-saiko-to,+a+Japanese+herbal+medicine,+on+hepatic+fibrosis+in+rats.">Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats.</a> Hepatology. 29 (1), 149-160 (1999).</li><li>Wang, Y., Gao, J., Zhang, D., Zhang, J., Ma, J., Jiang, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+insights+into+the+antifibrotic+effects+of+sorafenib+on+hepatic+stellate+cells+and+liver+fibrosis.">New insights into the antifibrotic effects of sorafenib on hepatic stellate cells and liver fibrosis.</a> J Hepatol. 53 (1), 132-144 (2010).</li><li>Machholz, E., Mulder, G., Ruiz, C., Corning, B. F., Pritchett-Corning, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Manual+Restraint+and+Common+Compound+Administration+Routes+in+Mice+and+Rats.">Manual Restraint and Common Compound Administration Routes in Mice and Rats.</a> J Vis Exp. (67), (2012).</li><li>Lee, G., Goosens, K. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sampling+Blood+from+the+Lateral+Tail+Vein+of+the+Rat.">Sampling Blood from the Lateral Tail Vein of the Rat.</a> J Vis Exp. (99), (2015).</li><li>Parkinson, C. M., O'Brien, A., Albers, T. M., Simon, M. A., Clifford, C. B., Pritchett-Corning, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+Necropsy+and+Selected+Tissue+and+Sample+Collection+in+Rats+and+Mice.">Diagnostic Necropsy and Selected Tissue and Sample Collection in Rats and Mice.</a> J Vis Exp. (54), (2011).</li><li>Ruehl-Fehlert, C., Kittel, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Revised+guides+for+organ+sampling+and+trimming+in+rats+and+mice--part+1.">Revised guides for organ sampling and trimming in rats and mice--part 1.</a> Exp Toxicol Pathol. 55 (2-3), 91-106 (2003).</li><li>Ishak, K., Baptista, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Histological+grading+and+staging+of+chronic+hepatitis.">Histological grading and staging of chronic hepatitis.</a> J Hepatol. 22 (6), 696-699 (1995).</li><li>Sant'Anna, L. B., Sant'Anna, N., Parolini, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Application+of+computer+assisted+image+analysis+for+identifying+and+quantifying+liver+fibrosis+in+a+experimental+model.">Application of computer assisted image analysis for identifying and quantifying liver fibrosis in a experimental model.</a> J Comput Interdiscip Sci. 2 (2), 139-148 (2011).</li></ol>

We have described a method to make an animal model of liver fibrosis and to assess the severity of liver fibrosis. It is important to deliver the correct dose of DMN and adhere to the schedule of weekly intraperitoneal injections. As the experiment progresses, it is crucial to weigh the rats and re-calculate the dose at the start of each week of DMN injections. Keep in mind that DMN is toxic and needs to be handled in the fume cabinet. We perform the intraperitoneal injections in the fume cabinet as well. With the need f...

DMN is a potent liver specific toxin. Its metabolism, tissue distribution, and ability to cause injury to livers of rats was reported by Magee1, and the mechanism of hepatocyte damage and cell death by apoptosis was described by Pritchard and Butler2. Intermittent administration of this compound was reported to induce liver fibrosis in dogs and rats3,4.
The mechanisms and morphologic changes of liver fibrosis have been extensively investigated using this model. In early studies using the rat, 3-week treatment with DMN produced centrilobular hemorrhagic necrosis followed by micronodular cirrhosis without steatosis5. It was shown that in early fibrosis, the collagen formed was more cross linked with type III being more prominent than type I6. In common with other causes, DMN-induced fibrotic changes were associated with an increase in Kupffer cells; hepatic macrophages that reside in the sinusoids. These cells morph into myofibroblasts and produce excessive amounts of extracellular matrix which is the primary problem in fibrosis7.
In terms of cellular signaling, Nakamura et al. demonstrated that TGF-&#946; plays a critical role in the progression of liver fibrosis8. They used an adenovirus expressing a truncated type II TGF-&#946; receptor, to specifically inhibit TGF-&#946; signaling. Liver fibrosis in these rats was spectacularly halted during DMN treatment when compared to control groups. Other studies have confirmed that suppression of TGF-&#946; leads to alleviation of liver fibrosis development9,10. The model was also used in a global gene profiling study to identify other fibrosis markers and proteins which could be used as drug targets for anti-fibrotic therapy11.
Other chemical agents used to induce liver fibrosis include thioacetamide (TAA) and carbon tetrachloride (CCl4). TAA was used first in rats and later in mice12. The advantages of this model include: ease of chemical administration in drinking water, the reproducibility of the model with characteristic micronodular cirrhosis and biochemical changes. The disadvantages include: the long time period of 3 months for liver fibrosis to develop and the lack of understanding of the molecular mechanism for induction of liver fibrosis. As for CCl4, its use has declined for the following reasons: it does not mimic human liver disease, has harmful effects on the ozone layer, causes pain and distress to animals, is very toxic to humans and requires extra precautions in its handling and disposal13,14.
Prolonged bile duct obstruction (by surgical intervention) as an experimental model for liver cirrhosis was first reported by Kountouras et al.15. This method is nontoxic to humans and animals. However, the time required for liver fibrosis to develop varies. A review of 30 reports by Marques et al.16, found that it took from seven days to four weeks after surgery for liver fibrosis to develop. The pathological changes described mimic those of human chronic biliary fibrosis and the model would be more suited for researchers interested in this area.
In summary, the intermittent administration of a constant dose of DMN in the rat over 4 weeks produces liver fibrosis that mimics the human disease. Dosed rats show progressive development of liver damage and parenchymal fibrosis4,17. Disease progression and severity can be monitored via blood samples or sacrifice of animals at specific time points and the effect is highly reproducible18. Thus the model has been widely used to study the mechanisms of liver fibrosis and cirrhosis as well as to screen for potential anti-fibrotic agents10,19,20.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Dimethylnitrosamine</td>
			<td>Wako</td>
			<td>147-03781</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Formalin</td>
			<td>Sinopharm chemicals</td>
			<td>F63257009</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethanol</td>
			<td>Sigma</td>
			<td>64-17-5</td>
			<td></td>
		</tr>
		<tr>
			<td>Xylene</td>
			<td>Fisher</td>
			<td>1330-20-7</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Masson trichome stains</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Aniline Blue</td>
			<td>Electron Microscopy Sciences</td>
			<td>#42755</td>
			<td></td>
		</tr>
		<tr>
			<td>Acid Fuschin</td>
			<td>Electron Microscopy Sciences</td>
			<td>RT42685</td>
			<td></td>
		</tr>
		<tr>
			<td>Scarlet Red</td>
			<td>Electron Microscopy Sciences</td>
			<td>#26905</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphotungstic Acid Hydrate</td>
			<td>ALFA AESAR</td>
			<td>ALFA40116.4</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphomolybdic Acid Hydrate</td>
			<td>Sigma SG</td>
			<td>221856-25G</td>
			<td></td>
		</tr>
		<tr>
			<td>Weigert&#39;s Iron Hematoxilyn</td>
			<td>Merck</td>
			<td>1.15973.0002</td>
			<td></td>
		</tr>
		<tr>
			<td>DPX Mounting Medium</td>
			<td>Merck</td>
			<td>HX066873</td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td></td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Tissue processor</td>
			<td>Leica</td>
			<td>Leica TP 1020</td>
			<td></td>
		</tr>
		<tr>
			<td>Embedding machine</td>
			<td>Sakura</td>
			<td>&#160;Sakura Tissue Tek TEC5 Embedding System</td>
			<td></td>
		</tr>
		<tr>
			<td>Microtome</td>
			<td>Leica</td>
			<td>Leica RM 2235</td>
			<td></td>
		</tr>
		<tr>
			<td>Vet Test Analyzer</td>
			<td>Idexx</td>
			<td>Vet Test 8008</td>
			<td></td>
		</tr>
	</tbody>
</table>

the dimethylnitrosamine induced liver fibrosis model in the rat

Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg dimethylnitrosamine (DMN), given intraperitoneally for three consecutive days per week. Intraperitoneal injections were performed in the fume hood as DMN is a known hepatoxin and carcinogen. The model has several advantages. Firstly, liver changes can be studied sequentially or at particular stages of interest. Secondly, the stage of liver disease can be monitored by measurement of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. Thirdly, the severity of liver damage at different stages can be confirmed by sacrifice of animals at designated time points, followed by histological examination of Masson&#39;s Trichome stained liver tissues. After four weeks of DMN dosing, the typical fibrosis score is 5 to 6 on the Ishak scale. The model can be reproduced consistently and has been widely used to assess the efficacy of potential anti-fibrotic agents.

DMN treated rats lose weight and become less vigorous with ruffled hair coat. There is significant loss in average body weights of DMN treated rats; first detectable after 2 weeks of DMN treatment, and this difference remains through weeks 3 and 4 after DMN treatment (Figure 1a). As the rats receive DMN over successive weeks, damage to the liver causes it to become smaller. The liver index; which is the percent of liver weight at final body weight was significantly lower ...

Watch this Scientific Journal Video about The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat at JoVE.com

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat

We describe a method to produce an animal model of liver fibrosis in the rat, and assess the degree of fibrosis by histological examination of the liver. The model can be used to study the development of liver disease as well as to test the efficacy of potential anti-fibrotic agents.

Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg ...

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