• Korean Journal of Clinical Pharmacy
• /
• v.9 no.1
• /
• pp.55-61
• /
• 1999

The object of this work was to study the pharmacokinetic differences and the cause of these differences in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride treatment when aminophylline (8 mg/kg as theophylline, i.v.) was injected. The concentrations of theophylline and its major metabolite (1,3-dimethyluric acid) in plasma were determined by HPLC. In addition, formation of 1,3-dimethyluric acid from theophylline in microsomes was determined. In cirrhotic rats, the systemic clearance of theophylline was reduced to $17\%$ of the control value while AUC (area under the plasma concentration-time curve) and $(t_{1/2})_{\beta}$ were increased to about 6 fold and 10 fold, respectively. The formation of 1,3-dimethyluric acid was decreased to $33-41\%$ of the control value in microsomes of cirrhotic rat liver. From these results, it can be concluded that in cirrhotic rats induced by N,N-dimethylnitrosamine or carbon tetrachloride the total body clearance of theophylline is markedly reduced due to a reduced hepatic metabolism.

• Environmental Analysis Health and Toxicology
• /
• v.20 no.3 s.50
• /
• pp.237-242
• /
• 2005

This study il focused on the hepatopreventive effect in cirrhotic rats induced by N, N -dimethylnitrosamine treatment when organir Lulfur -containing compoundE were orally injected. Biochemical parameters (aspatate transaminase (AST), alanine transaminase (ALT) alkaline phosphatase (ALP), 1-protein and t-bilirubin) were measured in serum injured liver tissue. The increased AST and ALT values were significantly reduced by organic sulfur-containing compounds at the oral dotes of 50 mg/kg. The result of morphological changes have illustrated the accumulation of liver damages, Each as inflammatory cell accumulation and cirrhosis, caused by N, N-dimethylnitrosamine. Also, it was found that liver damages were prevented by the treatment of organic sulfur- containing compounds.

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

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

• Korean Journal of Pharmacognosy
• /
• v.34 no.1 s.132
• /
• pp.60-64
• /
• 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.

• YAKHAK HOEJI
• /
• v.30 no.1
• /
• pp.8-13
• /
• 1986

It has been assumed that nitrite, one of the precursor of N-nitrosamine, in human saliva must have been formed from salivary nitrate through the action of microorganism in the oral cavity. In this paper, we have tested the concentration of nitrite and nitrate in human saliva and the degrees of nitrate reduction by oral microflora and identified some bacteria which were able to reduce nitrate. The concentration of nitrite and nitrate was 1.7~9.5ppm and 9.0~28.5ppm respectively. The numbers of total bacteria and nitrate reducing bacteria in four korean human saliva sample were 15~63${\times}10^8$ CFU and 1.0~6.0${\times}10^8$ CFU and the main nitrate reducing bacteria were Streptococcus uberis which was presented in large quantities and showed remarkable reductive activity. Lastly, we knowed that N-dimethylnitrosamine was formed by the reaction between dimethylamine and nitrite in the presence of St. uberis in vitro.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.172.2-173
• /
• 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
• /
• 2003.04a
• /
• pp.181.1-181.1
• /
• 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)

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.180.1-180.1
• /
• 2003

Proanthocyanidins, one of the major natural polyphenolic compounds of grape has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the hepatoprotective effect of proanthocyanidins on the dimethylnitrosamine (DMN)-induced liver damage in rats. Oral administration of proanthocyanidins (20, 50mg/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. (omitted)

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.288.2-288.2
• /
• 2002

Herbal medicines are increasingly being utilized to treat a wide variety of disease processes. We previously reported that aqueous extract from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil (CK). had hepatoprotective effects against acetaminophen induced liver injury. In the present study, we assayed the preventive and therapeutic effects of CK on experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. (omitted)