• Parasites, Hosts and Diseases
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• v.31 no.1
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• pp.21-30
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• 1993

The study was carried out to observe the effects of Clonorchis sinensis Infection on induction of cholangiocarcinoma in Syrian golden hamsters to which 15 ppm dimethylnitrosamine (DMN) solution was administered for 8 weeks. The histopathological changes of the bile duct and liver cells were observed at the 11th week. In six of 8 hamsters (75%) which were treated with DMN and then infected with C. sinenis, the livers developed cholangiocarcinoma at 10 weeks after the infestation of C. sinenis. The features of cholangiocarcinoma lesions were adenomatous or papillary hyperplasia of the bile duct epithelia showing distinct anaplastic changes with mucinous cell metaplasia and necrotic area. In the hamsters which received either DMN or C. sinenis alone, the livers showed only hyperplastic changes of the bile duct epithelial cells. It was suggested that C. sinensis infection and DMN administration could be a synergism on the development of cholangiocarcinoma in Syrian golden hamsters.

• 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.

• Korean Journal of Pharmacognosy
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• v.34 no.1 s.132
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• pp.60-64
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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. SL also increased serum protein level and reduced the hepatic level of malondialdehyde in DMN-treated rats. Furthermore, DMN-induced elevation of hydroxyproline content was reduced by the treatment of SL. In conclusion, these results demonstrated that SL exhibited in vivo hepatoprotective effect against DMN-induced liver injury, and suggest that SL may be useful in the prevention of liver damage.

• 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

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.84-94
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• 1991

The purpose of this study was to evaluate the influence of high does carbon tetrachloride($CCl_4$) on the hepatotoxic effect of dimethylnitrosamine(DMN) which induces acute hemorrhagic necrosis in liver. Rats were injected intraperitoneally DMN dissolved in physiologic saline by a dose of 40mg/kg. For changes related to $CCl_4$ pretreatment, rats were injected intraperitoneally $CCl_4$ dissolved in olive oil by a dose of 0.4mg/kg, and then injected DMN. The livers were extracted from the rats 3, 6, 12, 24, 48, 72, and 120 hours after $CCl_4$ and/or DMN injection. Liver tissues were examined with light and electron microscopes. The results were summarized as follows ; Light microscopic findings : Severe centrilobular hemorrhagic necrosis developed from 12 hours after injection of DMN and continued to 120 hours. On injection of DMN after $CCl_4$ pretreatment, Massive necrosis occurred early. But active regenerative changes were produced in 24 hours. In 120 hours, the liver recovered in almost normal appearance. The degree of necrosis in pretreated group was similar to that in DMN injection only, and the time of recovery was faster in preteated group. Electron microscopic findings ; The early change was mainly disorganization of RER in DMN injection, and clumping and vesicular dilatation of ER in injection of $CCl_4$. In pretreatment group the early change was similar in appearance with $CCl_4$ group, but severer in degree. According to the results, it was revealed that acute toxic effect of DMN was recovered more rapidly in pretreatment group. Thus it was suggested that $CCl_4$ had protective effect in DMN hepatotoxicity.

• Journal of Yeungnam Medical Science
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• v.4 no.1
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• pp.89-96
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• 1987

Carbon tetrachloride and Dimethylnitrosamine, both potent hepatotoxic agents, affect the hepatic lobules with fatty changes and central necrosis, and hemorrhagic necrosis. To study the effects on morphologic changes of the hepatic lobules in cases of single and repeated treatment of both hepatotoxins, sublethal doses of carbon tetrachloride, 0.4ml/kg, and dimethylnitrosamine, 40mg/kg of rats were given intraperitoneally single, twice and triple. With interval of 3 days, and the results were as follows : 1. The fatty changes and central necrosis of the hepatic lobules were milder and more quickly disappeared in the rats with twice or triple treatment than single administration of carbon tetrachloride, and regenerative changes of hepatic and sinusoidal cells achieved fater in the rats with repeated administration of carbon tetrachloride than those with single treatment. 2. The hemorrhagic necrosis of the hepatic lobules was not significantly influenced by the times of DMN treatment, but the hyperplastic changes showed more active to animals, with multiple administration of DMN.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.413-418
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• 2004

Objectives : Cirsii Japonici Herba (CJH) is one of medicinal plants that has been frequently used for styptic purposes in Asian countries. In order to evaluate a hepatoprotective effects of CJH in the liver fibrotic diseases, the present study investigated how CJH improves a hepatic function in the dimethylnitrosamine(DMN) treated rat. Methods : CJH were orally administered to rats that has been treated with DMN. Subsequently, the amount of blood L-asparate aminotransferase (AST), L-alanine aminotransferase (ALT), and hydroxyproline were quantitated. Several histopathological markers for examining the degree of hepatic fibrosis were investigated by H-E and Masson-Trichrome staining. Results: DMN treatment caused a increase of relative liver weight to the body at 14 days after DMN induction, Administration of CJH with 100mg/kg and 1,000mg/kg dose decreased significantly the AST level elevated by DMN injection(p<0.01). But ALT level was not improved. The hydroxyproline level was reduced by a simultaneous treatment of CJH with DMN for 7 days, but not recovered completely to its normal value, CJH administration improved conspicuously the DMN-induced histopathological changes of liver such as granuloma, but cell necrosis and fibrosis were not improved with CJH 1,000mg/kg dose. Conclusion: These results indicate that CJH has protective effect on liver injury and can inhibit liver fibrosis Induced by DMN in rats.

• 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.172.2-173
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• 2003

Naringenin, a phytoalexin found in grapefruit. has been reported to exhibit a wide range of pharmacological properties. The aim of the present study is to evaluate the protective effect of naringenin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Fibrosis was induced by intraperitoneal injection of DMN. Naringenin was given orally at 20 mg/kg and 50 mg/kg daily for 4 weeks. (omitted)

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.181.1-181.1
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• 2003

Polyphenolic compounds have been reported to exhibit a wide range of pharmacological properties. In this study. we investigated the hepatoprotective effect of skin and seed of grape which contain abundant polyphenol compounds on dimethylnitrosamine(DMN)-induced liver damage in rats. Ingestion of skin and seed of grape (10％ diet, 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. (omitted)