The study was done to investigate the effects of the extracts from the different parts of Lythrum salicaria (LS) on liver protective activities in chronically alcohol-treated rats. SD male rats except normal animals were administrated with alcohol ($30m{\ell}$ of 30%~40% ethanol/kg/day) and the extracts (300 mg/kg/day) for 10 weeks. Chronic alcohol administration decreased body weight, high density lipoprotein (HDL)-cholesterol and the reduced form-glutathione (GSH), whereas increased the ethanol content, glutamic-oxaloacetic transaminase (GOT), total cholesterol, low density lipoprotein (LDL)- cholesterol, triglyceride in blood/serum and the ratio of the oxidized form of glutathione (GSSG) and total GSH (GSSG/total GSH) in liver tissue. Groups treated with the extracts of leaf, root and stem, showed decrease in GOT, total cholesterol and GSSG/total GSH and increase in hepatic aldehyde dehydrogenase (ALDH), total GSH and serum albumin. Administration with the root extract of LS decreased blood ethanol content compared with the other part extracts. But, serum triglyceride values in rats treated with root and stem extract were higher than that of the negative control animals. Flower extract-fed group showed decrease in body weight and serum triglyceride, but increase in the ratio of GOT and glutamic-pyruvic transaminase (GPT), and GSSG/total GSH. From the results, we conclude that the extracts of root and leaf among the plant parts of LS might be useful for the amelioration of the chronic alcohol-induced liver demage of rat.
To evaluate an effect of xanthine oxidase(XO) reaction system on the carbon tetrachloride($CCl_4$) metabolism, $CCl_4$ was given twice at 0.1ml/100g body wt. at intervals of 18 hour to the rats and those pretreated with allopurinol (50mg/kg. body wt.). The influence of XO on the metabolism of $CCl_4$ was focused on the degree of liver damage and the activities of a $CCl_4$ metabolizing marker enzyme, glucose-6-phosphatase. The increasing rate of liver weight per body weight and the levels of serum alanine aminotransferase to the control group were more decreased in allopurinol-pretreated rats than in those treated with $CCl_4$ alone. The liver XO activities were more increased in $CCl_4$-treated rats than the control group and the $CCl_4$-treated rats pretreated with allopurinol showed a decreased activities of XO compared to the $CCl_4$-treated rats. The type conversion (type D --> type O) rate was more decreased tendency in allopurinol pretreated rats than those treated $CCl_4$ alone. In dialyzed liver enzyme preparations, all of the xanthine oxidase activities: $CCl_4$-treated, allopurinol and $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the control group, but similar Km value. Moreover, $CCl_4$-treated rats pretreated with allopurinol showed the more increased Vmax value than the group treated with $CCl_4$ alone. In conclusion, it can not be negate the possibility of metabolism of $CCl_4$ by the xanthine oxidase enzyme system.
Kim, Young-Ju;Jeong, Jae-Min;Kim, Seok-Ki;Son, Mi-Won;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
The Korean Journal of Nuclear Medicine
/
v.37
no.5
/
pp.301-307
/
2003
Purpose: Lipiodol is used for targeting liver cancers by administrating through the hepatic artery. In the present study, feasibility of Re-188-sulfur colloid suspension in lipiodol as a liver cancer targeting agent was investigated. Materials and Methods: Re-188-sulfur colloid was prepared, harvested by centrifugation, washed with organic solvent and then suspended into lipiodol. Biodistribution of Re-188-sulfur colloid in normal saline and its suspension in lipiodol in mice after 1 hr of injection through the tail vein were investigated. Biodistribution and autoradiography of tumor-hearing liver was acquired after 5 min post-injection into left ventricle of the tumor-inoculated rats. Results: After 1 hr of injection with Re-188-sulfur colloid suspensiob in lipiodol through the tail vein in normal mice (n=3), the uptakes in the liver and lung were $5.2{\pm}0.7\;and\;91.0{\pm}1.7%$ ID/organ, respectively. After 5 min of injection with Re-188-sulfur colloid suspention in lipiodol through the left ventricle in the tumor-inoculated rats (n=4), uptakes in the normal liver, hepatoma, and lung were $0.41{\pm}0.28,\;1.88{\pm}1.57,\;and\;1.65{\pm}1.54%$ ID/organ, respectively. And autoradiography of hepatoma showed increased uptake than normal liver tissues. Conclusion: Re-188-sulfur colloid suspension in lipiodol injected through the artery shows higher uptake in the hepatoma than normal liver tissue that indicates the feasibility as a new radiopharmaceutical for therapy of hepatoma.
Objectives : This study was undertaken to verify the effects of Gyeongshingangjeehwan18 (GGEx18) on obesity using ob/ob male mice. Methods : Eight-week old mice (wild-type C57BL/6J and ob/ob) were used for all experiments. Wild-type C57BL/6J mice were used as lean control and obese ob/ob mice were randomly divided into 5 groups: obese control, GGEx15, GGEx16, GGEx17, and GGEx18. After mice were treated with several kinds of GGEx for 11 weeks, body weight gain, feeding efficiency ratio, plasma lipid and glucose metabolism. Results : 1. Compared with obese controls, GGEx-treated mice had lower body weight gain and feeding efficiency ratio, the magnitudes of which were prominent in GGEx16 and GGEx18. 2. Consistent with their effects on body weight gain, GGEx16 and GGEx18 not only decreased plasma triglycerides levels, but also increased HDL-cholesterol concentration. 3. CT analysis revealed that visceral fat areas were decreased in all treatment groups compared with obese control mice. The decrease in visceral fat area was prominent in GGEx16 and GGEx18, although they were not statistically significant. 4. The size of adipocytes were significantly decreased by GGEx18, whereas the adipocyte number per unit area was significantly increased, suggesting that GGEx18 decreased the number of large adipocytes. Hepatic lipid accumulation was decreased by GGEx16 and GGEx18, and the inhibitory effect was most effective in GGEx18. 5. Plasma GOT and GPT concentrations were significantly lower following GGEx16 and GGEx18 treatment compared with obese controls. Organ weights were not changed by GGEx treatment, indicating GGEx do not show any toxic effects. Conclusions : These results suggest that GGEx may regulate obesity. Of the 4 compositions, GGEx18 seems to be most effective in improving obesity and lipid disorders.
The contents of bioactive materials (e.g. polyphenolics compounds, flavonoids, minerals, and fatty acids) and antioxidative activities (DPPH (${\alpha}$,${\alpha}$'-diphenyl-${\beta}$-picrylhydrazyl) free radical scavenging activity, peroxidation of linoleic acid and rat hepatocyte microsome, and Fe/Cu reducing power) were tested by in vitro experimental models using water, ethanol and methanol extracts of leaves (TOL) and fruits (TOF) from Thuja orientalis. Methanol extract from TOL showed the highest extraction yield (12.90%) as well as contents of polyphenolic compounds (16.02%) and flavonoids (0.25%). Major minerals were Ca, K, and Mg. Major fatty acids were palmitic and lauric acids in TOL and palmitic and decanoic acids in TOF. In oxidation of in vitro models using DPPH free radical scavenging activity, Fe/Cu reducing power, $Fe^{2+}$/ascorbate-induced linolenic acid peroxidation by ferric thiocyanate and thiobarbituric acid (TBA) methods, and autooxidation of rat hepatic microsomes membrane, anti-oxidative activities were stronger in all extracts of TOL than in those of TOF in a dose-dependent manner. From these results, methanol extract of TOL was shown to have the most potent anti-oxidative properties and the highes content of antioxidative compounds such as polyphenolic compounds and flavonoids.
This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.
[here are so many reports that pulsatile blood flow provides physiologic organ perfusions during cardiopulmonary bypass. So, we compared the recent 30 cases undergoing cardiac surgery by Cobe-Stckert pulsatile roller pump with another 30 cases by Polystan nonpulsatile roller pump. Pulsatile flow was applied during aortic-cross clamping period when synchronized to internal EKG simulator, and perfusion mode was changed to continuous nonpulsatile flow after declamping of aorta. Age, sex, weight, and disease entities were comparable and operative techniques were similar between two groups. 1. There were no differences in average ACC time, ECC time, and Operation time. 2. Postoperative artificial respiration time was 6hrs 30mins in nonpulsatile group and 4hrs 48mins in pulsatile group, and detubation time after ventilator weaning was 2hrs 44mins in nonpulsatile group and 1hrs 43mins in pulsatile group. 3. Average pulse pressure was 8mmHg in nonpulsatile group and 55mmHg in pulsatile group, and a mean arterial pressure was 66.0mmHg in nonpulsatile group and 60.7mmHg in pulsatile group. 4. Mean urine-output during ACC;ECC period was 9.717.3;9.913.2ml/kg/hr in nonpulsatile group and 14.215.0;15.817.5 in pulsatile group [p<0, 05], and thereafter progressive decrease of differences in urine output between two groups until POD 2, and lesser amounts of diuretics was needed in pulsatile group during same postoperative period. Serum BUN/Cr level showed no specific difference and urine concentration power was well preserved in both groups. 5. Plasma proteins and other Enzymes showed no differences between two groups, but serum GOT/GPT level was higher in nonpulsatile group till POD 2. 6. Serum Electrolytes showed no differences between two groups. 7. WBC, RBC, Platelet counts, Hgb and Hct were not different and Coagulogram was well preserved in both groups. 8. Plasma free Hgb level was 7.09mg% in pulsatile group compared with 3.48mg% in pulsatile group on POD 1 but was normalized on POD 2. Gross hemoglobinuria after ECC was noted in 6 cases [20%] of pulsatile group and 4 cases [13%] of nonpulsatile group. 9. In both groups, most patients were included in NYHA class III to IV [28 cases;93% in nonpulsatile group, 22 cases;73% in pulsatile group] preoperatively, and well improved to class I to 11[22 cases; 73% in nonpulsatile group, 30 cases; 100% in pulsatile group] postoperatively. There were 7 operative mortalities in nonpulsatile group only, which were 5 cases of TOF with hepatic failure, 1 case of multiple VSDs with low out-put syndrome, and 1 case of mitral valvular heart disease with cardiomyopathy. We concluded that the new, commercially available Cobe-Stckert pulsatile roller pump device was safe, simple, and reliable.
This study was attempted to investigate the effect of 'Angelicae gigantis Radix extract (AG.EX.)' and 'Angelicae acutilobae Radix extract (AA.EX.)' on the activities of GOT, GPT and alkaline phosphatase (A1.P), the contents of total cholesterol in serum of $CCl_4$ and D-galactosamine intoxicated rats, and the weight change ratio of body, liver and spleen in $CCl_4-intoxicated-rats$ by administering the extract of 300 and 500 mg/kg P.O.. Significant test was performed by comparision with the biochemical values between intoxicated-control group and extract-administered group. The activities of s-GOT, s-GPT and the contents of total cholesterol elevated by $CCl_4-intoxication$ were significantly decreased in all dose (300, 500 mg/kg) of Angelicae gigantis Radix-water extract (AG.WEX.) and alcohol extract (AG.AEX), and Angelica acutilobae Radix-water extract (AA.WEX.) and alcohol extract (AA.AEX.), respectively, as compared with the control group. And administered group of 300 mg/kg showed more significant decreasing effect than 500 mg/kg, and more significantly decreased in water extract of AG.EX. and ethanol extract of AA.EX. But in the activities of s-A1.P. inhibition effect were significantly decreased only in a dose of 300 mg/kg of AA.WEX. and AA.AEX. The activities of s-GOT and s-GPT elevated by D-galactosamine were not decreased in all samples, as compared to intoxicated-control group. But the activities of s-Al.p was significantly decreased as compared with control groups, in all samples and administration of 300 mg/kg was more significantly decreased than 500 mg/kg. The contents of total cholesterol remarkably decreased than the normal groups by D-galactosamine intoxication was not recovered in all samples. The increasing rate of the body weight increased by $CCl_4-intoxication$ were not decreased than the $CCl_4-control$ group in all sample groups. The increasing rate of liver weight increased by $CCl_4-intoxication$ were significantly decreased in 300 mg/kg of AA.AEX.AG.WEX. and AA.WEX., respectively, as compared with $CCl_4-control$ group.
Background: Up to 90% of a theophylline dose is biotransformed, by interaction with one or more the variants of the cytochrome P-450 drug metabolism system. Macrolides affect the elimination of theophylline by influencing on the microsomal enzyme systems. We evaluate the effect of erythromycin and new macrolides on the serum theophylline level and clearance. Method : Subjects consisted of moderate asthmatic patients with normal renal and hepatic functions. All subjects were non-smokers and treated with oral theophylline 400 mg per day. We randomly assigned 53 patients into four groups. Each group was treated with one macrolides, the first group erythromycin(n:19, 500 mg bid), second roxithromycin (n:14. 150 mg bid), third clarithromycin (n:10, 250 mg bid) and fourth azithromycin(n:10, 250 mg bid). We measured the serum theophylline level and clearance at three intervals, at pretreatment, after the first and fourth week after receiving the following macrolides, erythromycin, roxithromycin and clarithromycin. When azithromycin was administered, the serum theophylline level was measured at pretreatment and after one week of treatment They were measured by a computerized program of Bayesian method. Results : When compared with control, erythromycin and roxithromycin-treated groups had a significantly elevated serum theophylline level and decreased clearance. However, there were no significant changes of the serum theophylline level and clearance in clarithromycin and azithromycin-treated groups. Conclusion : These results suggest that theophylline dose may need to be readjusted and have periodic drug monitoring when erythromycin or roxithromycin is administered concurrently.
A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.
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