• Toxicological Research
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• v.34 no.2
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• pp.85-95
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• 2018

The term Butterfly tea refers to decoction of Mariposa christia vespertilionis leaves which is widely consumed by cancer patients throughout Malaysia and has gained a huge popularity among Malaysians, not only cancer patients but also researchers to discover the real potential of this plant. Herein, the study is aimed at evaluating the possible toxicity in 28-day subacute oral toxicity of ethanolic extract M. christia vespertilionis in male Sprague Dawley rats. The 28-day subacute toxicity study was conducted to detect the no-observed adverse effect level (NOAEL). In this study, a total of 30 rats were divided into the control, 5% DMSO (vehicle), low dose (75 mg/kg), medium dose (125 mg/kg) and high dose (250 mg/kg) groups. The extract was administered daily from day 1 until day 28. At the end of the study, the animals were humanely sacrificed and assessed for the effect extract of Mariposa christia vespertilionis leaves on body weight and relative organ weights and haematological, biochemical and histopathological parameters. The haematological and serum biochemical parameters for the assessment of kidney and liver injuries were carried out. Results of haematological and serum biochemistry results showed no changes in the control and treated groups. In the histopathology, evaluation of kidney tissues in all treated groups showed no significant (p > 0.05) lesions. In contrast to kidney, liver tissues showed significant differences (p < 0.05) in lesions observed in low dose (430 mg), medium dose (700 mg) and high dose (1480 mg) groups with very mild, mild and mild to moderate lesion of hepatic necrosis, in the respective groups, and very mild hepatic degeneration and hepatitis were scored in all three groups.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.2
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• pp.123-130
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• 2019

In this study, we investigated the effects of MOK pharmacopuncture at high-doses which are increased 10 to 100-fold in clinics, on propylthiouracil (PTU)-induced hypothyroidism in rats and the safety. We measured the changes of body weight, food and water intake, body temperature, the serum levels of thyroid hormones (TSH, T3, and T4), AST and ALT, glucose, lipid metabolites (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride) and observed histopathological changes of thyroid tissues by H&E staining. We also analyzed the peaks of constituents of MOK using HPLC. In the results, the treatment of MOK pharmacopuncture at high-dose (30 mg/kg) in hypothyroidism-induced rats for 2 weeks was shown the improvement effects on the decrease of body weight, food intake, and body temperature, The MOK pharmacopunture at high dose regulated the imbalance of thyroid hormones, glucose, and lipid metabolites and also inhibited the structural damages of thyroid tissues. In liver damage, the MOK pharmacopuncture at high dose reduced the increase of AST and ALT levels in hypothyroid rats. We identified the MOK constituents in HPLC analysis. In conclusion, the treatment of MOK pharmacopuncture at high dose has a therapeutic effect on hypothyroidism without liver toxicity, suggesting that the MOK pharmacopuncture be usefully applicable to treat with hypothyroidism in clinics.

• BMB Reports
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• v.38 no.5
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• pp.563-570
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• 2005

Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced liver injury. A model of liver injury in female rats was done by intraperitoneal injection of TAM in a dose of $45\;mg\;Kg^{-1}\;day^{-1}$, i.p. for 7 successive days. GTE in the concentration of 1.5%, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in liver homogenate of tamoxifen-intoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations transaminase) levels. The oral administration of 1.5% GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases levels. The data obtained from this study speculated that 1.5% GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced liver injury in rats.

• Toxicological Research
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• v.24 no.2
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• pp.113-117
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• 2008

Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

• Korean Journal of Plant Resources
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• v.36 no.3
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• pp.198-206
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• 2023

The effectiveness of the extracts of Alnus japonica and Portulaca oleracea, which are effective in improving alcohol-induced liver damage, was confirmed using acute and chronic alcoholic liver injury animal models. In the acute alcoholic liver injury model, dieting Alnus japonica and Portulaca oleracea complex (ALPOC) at a dose of 50 mg/kg showed no significant change in liver or body weight, while measured plasma ALT activity to be deficient (28.12 U/ml) compared to the alcohol intake group (42.5 U/ml), and confirmed that restored it to an average level. It showed an improvement of 34.9% compared to the alcohol intake group. AST activity confirmed that it showed a very effective liver protection activity by showing a gain of 12.6%. The chronic alcoholic liver damage animal model demonstrated that ALT showed an improvement effect of 25%, and AST showed an effect similar to that of the positive control group, Hovenia extract. In addition, through H&E staining analysis, observed that the ALPOC improved the necrosis and bleeding of the liver. And the ALPOC group showed intense antioxidant activity of 127% or more compared to the alcohol intake group, and this was confirmed to have a very high activity, which is more than 20% higher than that of the hovenia fruit extract.

• Progress in Medical Physics
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• v.21 no.2
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• pp.165-173
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• 2010

In this paper, we evaluated the performance of 3D CRT, IMRT and three kind of RA plannings to investigate the clinical effect of RA with liver cancer case. The patient undergoing liver cancer of small volume and somewhat constant motion were selected. We performed 3D CRT, IMRT and RA plannings such as 2RA, limited triple arcs (3RA) and 3MRA with Eclipse version 8.6.15. The same dose volume objectives were defined for only CTV, PTV and body except heart, liver and partial body in IMRT and RA plannings. The steepness of dose gradient around tumor was determined by the Normal Tissue Objective function with the same parameters in place of respective definitions of dose volume objectives for the normal organs. The approach between the defined dose constraints and the practical DVH of CTV, PTV and Body was the best in 3MRA and the worst in IMRT. The DVHs were almost the same among RAs. Plans were evaluated using Conformity Index (CI), Homogeneity Index (HI) and Quality of coverage (QoC) by RTOG after prescription with dose level surrounding 98% of PTV in the respective plans. As a result, 3MRA planning showed the better favorable indices than that of the others and achieved the lowest MUs. In this study, RA planning is a technique that is possible to obtain the faster and better dose distribution than 3D CRT or IMRT techniques. Our result suggest that 3MRA planning is able to reduce the MUs further, keeping a similar or better targer dose homogeneity, conformity and sparing normal tissue than 2RA or 3RA.

• Journal of radiological science and technology
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• v.34 no.4
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• pp.341-349
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• 2011

This study was to measure the patient dose difference between 3D treatment planning CT and 4D respiratory gating CT. Study was performed with each 10 patients who have lung and liver cancer for measured patient exposure dose by using SOMATON SENSATION OPEN(SIMENS, GERMANY). CTDIvol and DLP value was used to analyze patient dose, and actual dose was measured in the location of liver and kidney for abdominal examination and lung, heart and spinal cord for chest examination. Rando phantom were used for the experiment. OSLD was used for in-vitro and in-vivo dosimetry. Increasing overall actual dose in 4D respiratory gated CT-simulation using OSLD increase the dose by 5.5 times for liver cancer patients and 6 times for lung cancer patients. In CT simulation of 10 lung cancer patients, CTDIvol value was increased by 5.7 times and DLP 2.4 times. For liver cancer patients, CTDIvol was risen by 3.8 times and DLP 1.6 times. The accuracy of treatment volume could be increased in 4D CT planning for position change due to the breaths of patient in the radiation therapy. However, patients dose was increased in 4D CT than 3D CT. In conclusion, constant efforts is required to reduce patients dose by reducing scan time and scan range.

• Journal of Microbiology and Biotechnology
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• v.15 no.4
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• pp.887-890
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• 2005

To evaluate the hepatoprotective activity of lactic acid bacteria, their effects on tert-butylperoxide (t-BHP)-induced hepatotoxicity in mice were measured. When lactic acid bacteria at doses of 0.5 and 2 g (wet weight)/kg were orally administered to mice with t-BHP-induced liver injury, these bacteria significantly inhibited the increase of plasma alanine aminotransferase and aspartate aminotransferase activities by $17-57\%$ and $57-66\%$ of the t-BHP control group, respectively. However, these lactic acid bacteria did not protect cytotoxicity induced by t-BHP against HepG2 cells. The inhibitory effects of these lactic acid bacteria at a dose of 15 g/kg were comparable with that of diphenyl dimethyl bicarboxylate at a dose of 0.2 g/kg, which has been used as a commercial hepatoprotective agent. Among these lactic acid Jacteria, Bifidobacterium longum HY8001 exhibited the most potent hepatoprotective effect. These orally administered lactic acid bacteria inhibited liver lipid peroxidation on t-BHP-induced hepatotoxicity of mice. We suggest that lactic acid bacteria may be an effective agent against liver injury.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.565-570
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• 1999

Intracellular accumulation of bile acids in the hepatocytes during cholestasis is thought to be pathogenic in cholestatic liver injury. Due to the detergent-like effect of the hydrophobic bile acids, hepatocellular injury has been attributed to direct membrane damage. However histological findings of cholestatic liver diseases suggest apoptosis can be a mechanism of cell death during cholestatic liver diseases instead of necrosis. To determine the pattern of hepatocellular toxicity induced by bile acid, we incubated primary cultured rat hepatocytes with a hydrophobic bile acid, Glycochenodeoxycholate (GCDC), up to 5 hours. After 5 hours incubation with $400\;{\mu}M$ GCDC, lactate dehydrogenase released significantly. Cell viability, quantitated in propidium iodide stained cells concomitant with fluoresceindiacetate was decreased time- and dose-dependently. Most nuclei with condensed chromatin and shrunk cytoplasm were heavily labelled time- and dose-dependently by a positive TUNEL reaction. These findings suggest that both apoptosis and necrosis are involved in hepatocytes injury caused by GCDC.

• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.389-399
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• 2004

Metallothionein (MT), a small protein molecule which can bind or release metal ions, is involved in the regulation of cellular metal homeostasis. This study was investigated the accumulation of cadmium in blood, tissue (liver, kidney and brain), and the effect of cadmium on several key genes (MT-I, MT-II, ZnT-1) in zinc metabolism in the mouse. Mouses weighing 20∼25 g were randomly assigned to control and cadmium treated group (Cd group). Cd group was intraperitoneally injected with cadmium 2, 4, 8 mg/kg and control group was administerd with saline. Mouses of each group were sacrificed by decapitation 4 hours after the administration of cadmium. Cadmium contents in blood, liver, kidney and brain were increased by a dose-dependent manner. Accumulation of cadmium was mainly occurred in liver and kidney. Induction of MT-I and MT-II protein was increased, but ZnT-1 expression was decreased in a dose-dependent manner by the treatment of 2∼8 mg/kg cadmium. These results suggested that cadmium can be transported to brain and alter the expression of several key genes in zinc homeostasis.