• Biomolecules & Therapeutics
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• v.16 no.1
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• pp.34-39
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• 2008

Oxidative stress may represent a common link between chronic liver damage and hepatic fibrosis. In the present study, we investigated activity changes of sphingomyelin catabolic enzymes, such as sphingomyelinases and ceramidases by using dimethylnitrosamine (DMN)-treated Sprague-Dawley (SD) male rats hepatic fibrosis model as a hepatic fibrosis model. Twenty rats divided into five groups received: (1) saline; (2) DMN for 1 week, (3) DMN for 2 weeks, (4) DMN for 3 weeks, and (5) DMN for 4 weeks by intraperitoneally 10 mg/kg of body weight for three consecutive days a week. Activities of acidic and neutral sphingomyelinases and acidic, neutral and alkaline ceramidases were measured in the liver and kidney from DMN-treated rats. We found increased ceramidase activities from 2-week and/or 3-week DMN treated rat livers compared to control rat liver. Acidic sphingomyelinase and alkaline ceramidase activities were significantly increased in 3-week DMN-treated rat kidneys compared to control rat kidney. Therefore, sphingolipid metabolizing enzymes and sphingolipid metabolites are supposed to be involved in liver fibrosis, although further investigation is necessary to elucidate meanings of sphingolipids during the liver fibrosis

• YAKHAK HOEJI
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• v.35 no.6
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• pp.522-529
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• 1991

The purpose of this research is to evaluate effects of chloramphenicol, phenobarbital and progesterone on damage of DNA, RNA and protein which was induced by dimethylnitrosamine. $N,N-Di[^{14}C]$ methyl-nitrosamine (DMN) was used as a damaging agent and levels of DNA, RNA and protein damage in liver, brain and pancreas were compared with a control group. Pretreatment of mice with chloramphenicol increased protein damage in pancreas two times more than the control level. Liver RNA damage was increased up to 5.8 times and brain DNA damage up to 6.95 times by treatment of phenobarbital but brain RNA damage was decreased significantly down to 21% of the control group. The damage of liver RNA was significantly decreased by treatment of progesterone, although liver protein damage, pancreas RNA damage and pancreas protein damage were increased.

• Herbal Formula Science
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• v.6 no.1
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• pp.119-139
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• 1998

This study was to investigate the protective and effects of Ikgukwhan and Ikgukbowhawhan on the liver cirrhosis or fibrosis induced by prolonged bile duct ligation; a new experimental model for cirrhosis and the intraperitoneal injection of dimethylnitrosamine in the rat. The development of fibrosis or cirrhosis and its inhibition by the two prescriptions were examined by the chemical analysis of AST, ALT, and hydroxyproline. The results obtained were as follows. 1. The increase of serum asparate aminotransferase induced by bile ductligation was inhibited by the administration of Ikgukwhan and Ikgukbowhawn extract. 2. The increase of serum alanine aminotransferase induced by bile duct ligation was inhibited by the administration of Ikgukwhan and Ikgukbowhawhan extract. 3. The increase level of serum AST and ALT induced by the intraperitoneal injection of dimethylnitrosamine was inhibited by the administration of Ikgukwhan and Ikgukbowhawhan extract. 4. The increase level of hydroxyproline volume in the damaged liver tissues in the rat was decreased by the oral administration of Ikgukwhan and Ikgukbowhawhan extract. But there were no significant differences in the inhibition rate between the two experimental groups.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.243-248
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• 2008

In the present study, we investigated activity change of sphingomyelin anabolic enzymes such as sphingomyelin synthase and ceramide synthase. Sprague-Dawley male rats treated with 10 mg/kg of DMN intraperitoneally were used as a hepatic fibrosis model. Sphingomyelin synthase and ceramide synthase activities were measured in 1-week, 2-week, 3-week and 4-week DMN-treated rats along with respective control group rats. We found the increased sphingomyelin synthase activity in 4-week DMN-treated liver but not in kidney. Ceramide synthase activity was significantly increased in DMN-treated kidney after 2-week treatment and in DMN-treated liver after 3-week treatment. Although further investigation is necessary to elucidate meanings of sphingolipid metabolites during the liver fibrosis, activity change of sphingolipid anabolic enzymes may imply that sphingolipid metabolism and sphingolipid metabolites could be involved in liver fibrosis especially under oxidative stress.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.179.3-180
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• 2003

Solanum lyratum (Solanaceae) has been used as a traditional analgesic, antipyretic and hepatoprotective agents in Korea. In this study, we investigated the hepatoprotective effect of ethylacetate extract of Solanum lyratum (SL) on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of SL (150, 300 mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase levels. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.122.1-122.1
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• 2003

Morin, one of the major natural flavonoids has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the hepatoprotective effect of morin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of morin (10, 20mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phospatase, and bilirubin levels. Morin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.116.2-116.2
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• 2003

Aspirin and aspirin-like nonsteroidal antiinflammatory drug have been the mainstay of therapy for rheumatoid arthritis. In this study, we investigated the hepatoprotective effect of aspirin on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of aspirin (7.5, 15mg/kg daily for 4 weeks) into the DMN-treated rats remarkably prevented the elevation of serum alanine transaminase, aspartate transaminase and alkaline phosphatase, and bilirubin levels. Aspirin also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.289.1-289.1
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• 2002

Quercetin, one of the most abundant flavonoids in human diet has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of quercetin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN caused a significant decrease in body and liver weight. Oral administration of quercetin (10 mg/kg daily for 4 weeks) remarkably prevented this DMN-induced loss in body and liver weight and inhibited the elevation of serum alanine transaminase. aspartate transaminase, and bilirubin levels. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.87-90
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• 2012

Cholangiocarcinoma (CCA) is the most common cancer in northeastern Thailand. At present, effective diagnosis of CCA either in humans or animals is not available. Monitoring the development and progression of CCA in animal models is essential for research and development of new promising chemotherapeutics. Ultrasonography has been widely used for screening of bile duct obstruction in CCA patients. In this study, we preliminarily investigated the applicability of ultrasonography to monitor the development and progression of CCA in Syrian golden hamsters (n=8) induced by Opisthorchis viverrini (OV)/dimethylnitrosamine (DMN) administration. Ultrasonography and histopathological examination of hamsters was performed at week 0, 20, 24 and 28 of OV infection or at the start of water/Tween-80 administration to controls. The ultrasonographic images of liver parenchyma and gallbladders of OV/DMN-induced CCA hamsters showed sediments in gallbladder, thickening of gallbladder wall, and hypoechogenicity of liver parenchyma cells. The ultrasonographic images of liver tissues were found to correlate well with histopathological examination. Although ultrasonography does not directly detect the occurrence of CCA, it reflects the thickening of bile ducts and abnormality of liver tissues. It may be applied as a reliable tool for monitoring the development and progression of CCA in animal models in research and development of new promising chemotherapeutics for CCA.

• Parasites, Hosts and Diseases
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• v.32 no.1
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• pp.13-18
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• 1994

Chronic Clonorchis sinensis (CS) infection Is etiologically related to cholangiocarcinoma (CHCA) in human and animals. This study was carried out to clarify the role of CS Infection on dimethylnitrosamine (DMN)-induced cholanglocarcinogenesis. Fifteen hamsters were administered with 15 ppm DMN for 4 weeks and one week later, the hamsters were infected with 15 metacercariae of CS (DMN→CS group). The other 15 hamsters were infected with CS and after 5 weeks they were treated with the drug, praziquantel. Again one week later, the hamsters were administered with DMN (CS→DMN group). The other IS hamsters were adulnistered with DMN and CS simultaneously (CS + DMN group) . Histopathological examination of the livers showed CHCA with papillary or adenomatous hyperplasia of bile ductules in 3 of 15 hamsters of DMN→CS group and in 11 of 15 hamsters of DMN + CS group. These results suggest that CS infection to hamsters may have a promoting effect on the development of CHCA.