• Journal of Pharmaceutical Investigation
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• v.36 no.1
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• pp.19-22
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• 2006

The pharmacokinetics of nimodipine, following a single 16 mg/kg oral dose, was investigated in rabbits with hepatic failure induced by 0.5 mL/kg (mild), 1.0 mL/kg (moderate) and 2.0 mL/kg (severe) of carbon tetrachloride $(CCl_{4}$ : olive oil = 20 : 80, v/v). The plasma concentrations of nimodipine were determined by a high performance liquid chromatographic assay. The levels of sGOT and sGPT in rabbits with mild $(86.2{\pm}29.0\;and\;98.5{\pm}33.1\;unit/dL)$, moderate $(168.1{\pm}61.2\;and\;196.2{\pm}66.0\;unit/dL)$ and severe $(292.7{\pm}82.2\;and\;314.2{\pm}99.8\;unit/dL)$ hepatic failure were significantly increased compared to the control $(38.0{\pm}10.1\;and\;32.4{\pm}10.2\;unit/dL)$. The area under the plasma concentration-time curve (AUC) of nimodipine was significantly increased in mild $(131.7{\pm}28.1%)$, moderate $(168.8{\pm}32.8%)$ and severe $(204.6{\pm}58.3%)$ carbon tetrachloride-induced hepatic failure rabbits compared to the control (100%) rabbits. The volume of distribution $(V_{d})$ and the total body clearance $(CL_{t})$ of nimodipine were significantly decreased in all hepatic failure groups. The elimination rate constant $(K_{el})$ of nimodipine was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. There was a correlation between sGOT (y= 1.01x+241, r=0.993) or sGPT (y=0.92x +243, r=0.997) value and the AUC of nimodipine in the rabbits with hepatic failure. These findings suggest that the hepatic metabolism of nimodipine was inhibited by carbon tetrachloride-induced hepatic failure rabbits, resulting in the decrese in $V_{d}$ and $CL_{t}$ of nimodipine in the rabbits with mild, moderate and severe hepatic failure.

• Journal of Life Science
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• v.12 no.2
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• pp.136-143
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• 2002

Jaboyangyeong-hwan (IAE) has been known as a traditional medicine for the treatment of debility, fatigue, and liver diseases. The hepatoprotective effect of the water extract of Jaboyangyeong-hwan was investigated against carbon tetrachloride ($CCl_4$)-induced hepatic damage. A single intraperitoneal injection of $CCl_4$produced liver damage in rats as manifested by the significant rise of aspartate aminotransferase (AST, alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in serum as compared to those of untreated normal group. Pretreatments of rats with the JAE extract (300, 600, and 1200 mg/kg for 7 days) were significantly reduced AST, ALT, and ALP levels compared with $CCl_4$-treated control group. Treatment of rats with $CCl_4$led to significantly increase in lipid peroxidation and significantly decrease in cytochrome P450 and P450 reductase. The oral administration of the JAE extract significantly inhibited the accumulation of microsomal thiobarbituric acid reactive substance (TBARS) and increased the cytochrome P450 and P450 reductase activity. All these biochemical alterations resulting from $CCl_4$administration were inhibited by the pretreatment with JAE extract. These results suggest that JAE water extract can be useful as a hepatoprotective agent.

• Preventive Nutrition and Food Science
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• v.12 no.1
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• pp.16-22
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• 2007

In order to evaluate the hepatoprotective effect of an herb distillate, ie., a mixture of 28 traditional Korean herbs, germanium, tormarine and Gijangsoo (Gijang water), $CCl_4$ was intraperitoneally administered to rats before or after supplementation of the diluted herb distillate (HD) for 2 weeks. Then hepatic xanthine oxidase activity and serum lipid profiles were determined. The experimental groups had higher feed intake than the normal control (NC), but had lower weight gain. Water intake and the amount of feces were not significantly different, but urine was excreted in lower amounts in all the experimental groups compared to the NC. Liver weights in the HD-supplemented groups were lower than that of the distilled water-supplemented groups (DW-groups) after $CCl_4$-administration. Serum ALT activities in all the experimental groups were higher than that of the NC-group. However, the increasing activity of serum ALT in the HD-supplemented groups (HD-groups) was lower than that of the DW-groups. Total serum and LDL-cholesterol levels were higher in all the $CCl_4$-administered groups than in the NC-groups, and serum HDL-cholesterol levels were lower in all the experimental groups compared with the NC-groups. Meanwhile, the increasing rate of total serum and LDL-cholesterol levels and the decreasing rate of HDL-cholesterol in the HD-groups were lower than that of the DW-groups. But, levels of serum TG were similar among all the experimental groups. The activities of hepatic xanthine oxidase (XOD) type O of the $CCl_4$-administered rats showed a significant increase in and an increasing rate of XOD in the HD-groups, which was lower than that of the DW-groups. On the other hand, GST activities in all the experimental groups were significantly decreased, and the decreasing rate was lower in the HD-groups than in the DW-groups. The hepatic contents of GSH and LPO in all the rats were not changed by $CCl_4$ administration. These results suggest that the decreased liver damage in the HD-supplemented groups was due to the inhibition of XOD-type O activity by constituents of HD, as well as by a prevention/inhibition of serum lipid profile changes in $CCl_4$-treated rats. However, further detailed studies are needed to support this hypothesis.

• Korean Journal of Clinical Laboratory Science
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• v.44 no.4
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• pp.229-238
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• 2012

Cyclooxygenase(COX-2) is an inducible enzyme that catalyzes the synthesis of prostaglandins (PGs) from arachidonic acid. Over-expression of COX-2 has been reported to be associated with progressive hepatic fibrosis in chronic hepatic C infection and rat liver fibrosis induced by carbon tetrachloride($CCl_4$). Recently, it is well known that mast cell products can stimulate the proliferation of hepatic stellate cells and key players in liver fibrosis. But little is known regarding their role in $CCl_4$-induced liver fibrosis in rat. Our aim was to investigate the relation between COX-2 expression and mast cells during liver fibrosis after $CCl_4$ treatment. Thirty Wistar rats were divided into five groups (non-treated 0, 2, 4, 6 and 8-week after $CCl_4$-treatment). Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were used to assess the expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), collagen-1 and COX-2 in liver tissue from $CCl_4$-treated rats. The density of collagen and mast cells were determined using a computerized image analysis system in liver sections stained with picrosirius red and toluidine blue, respectively. The expression levels of ${\alpha}$-SMA, collagen-1 and COX-2 mRNA were significantly higher at 2 wk in $CCl_4$-treated groups than non-treated group. The number of mast cells in liver tissues increased gradually from 2 wk to 6 wk depending on the fibrosis severity but decreased abruptly at 8 wk. The significant increase of collagen-1 and ${\alpha}$-SMA mRNA expression in $CCl_4$-treated rats was continued until 6 wk while the COX-2 mRNA was significantly decreased at 8 wk. These results suggest that increased mast cells are closely associated with COX-2 over-expression during hepatic fibrogenesis of $CCl_4$-treated rats.

• Archives of Pharmacal Research
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• v.18 no.3
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• pp.179-182
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• 1995

Previous study showed that $CCl_4$ administration evoked a rapid decrease in cytochrome $P_{450}$ 2E1 protein soon after the exposure due to posttranslational inhibition(Biochem. Biophys. Res. Commun. 179:449-454, 1991). In this report, aniline hydroxylase and the amounts of immunoreactive $P_{450}$ 2E1 were rapidly decreased during day 1 to 2 and recovered during day 3 to 4 after a single dose of $CCl_4$. The activity of pentoxyresorufin-O-dealkylase was also suppressed at day 1 and began to repair from day 2. However, the decrease in immunoreactive $P_{450}$ 2C content was not observed. The decreases in $P_{450}$ 2E1 enzyme activity and immunoreactive protein by acute $CCl_4$ treatment were accompanied by a decline in $P_{450}$ 2E1 mRNA level. The data thus suggested a pretranslational reduction of $P_{450}$ 2E1 during day 1 to 2 after acute $CCl_4$ treatment.

• Journal of Radiation Industry
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• v.7 no.1
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• pp.81-85
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• 2013

This study was conducted to investigate the effect of fermented blackberry drinks (BD) on carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into four groups with 6 rats per group: control, $CCl_4$, $CCl_4$ plus BD $3ml\;kg^{-1}$, and $CCl_4$ plus BD $6ml\;kg^{-1}$. We found that the levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased and the activity of antioxidant enzyme glutathione peroxidase (GPx) in the liver was decreased in rats treated with $CCl_4$ alone when compared with the control group. However, the administration of BD attenuated the levels of serum AST and ALT in $CCl_4$-treated rats. Moreover, the administration of BD significantly increased the activity of GPx in $CCl_4$-treated rat livers. Taken together, these results suggest that BD could protect the liver from $CCl_4$-induced hepatic damage.

• Advances in Traditional Medicine
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• v.9 no.3
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• pp.225-231
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• 2009

The present study deals with the amelioration by Lagerstroemia speciosa Linn. leaf extract against hepatotoxicity induced by carbon tetrachloride ($CCl_4$), which was evaluated in terms of serum marker enzymes like serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, serum total bilirubin, total protein levels along with concomitant hepatic and antioxidants like superoxide dismutase, catalase, glutathione, glutathione peroxidase and lipid peroxidation enzymes were monitored. These biochemical parameters altered by the single dose level of $CCl_4$ (0.75 ml/kg body weight, i.p). Pre treatment with L. speciosa prior to the administration of $CCl_4$, at the doses of 50 and 250 mg/kg. body weight/day, p.o. for 7 days, significantly restored all the serum and liver tissue parameters near to the normal levels, respectively. Silymarin was used as a reference standard, prior to the administration of $CCl_4$ to rats. These findings indicate the protective potential of L. speciosa against hepato toxicity which possibly involve mechanism related to its ability of selective inhibitors of (reactive oxygen species like antioxidants brought about significant inhibition of TBARS suggesting possible involvement of $O_2{\cdot}-$, $HO_2{\cdot}$, and ${\cdot}OH$. In conclusion, the amelioration may be attributed to the synergistic effects of its constituents rather than to any single factor as the leaves are rich in tannins, sterols, flavonoids, saponins etc.

• YAKHAK HOEJI
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• v.40 no.3
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• pp.320-325
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• 1996

In order to evaluate the protective effects of galangin on $CCl_4$-induced hepatotoxicity, GOT, GPT and malondialdehyde(MDA) values were measured in ICR mice. Galangin,a flavonoid compound, was administered orally for six days and immediately $CCl_4$ was injected intraperitoneally after the last dose of galangin. Mice were sacrificed at 24h after the administration of $CCl_4$. In the multiple pre-treatments for 6 consecutive days, galangin showed more potent protective effects than silymarin as reference active compound in serum GOT, GPT and MDA values in the liver at all doses tested. Antioxidative activity was determined by measuring the amounts of MDA formed from ethyl linoleate by $H_2O_2$ in vitro. Galangin showed higher inhibition than silymarin. These results demonstrate a possible hepato-protective role of galangin against $CCl_4$-induced hepatotoxicity in vivo and $H_2O_2$-induced lipid peroxidation in vitro. Therefore, galangin may be capable of protecting hepatotoxicity.

• KSBB Journal
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• v.19 no.1
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• pp.12-16
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• 2004

Recently the measurement of biophoton emission has attracted increasing attention in the study on physiological state of biological systems. We report the measurements of biophoton emission from the mouse fatty liver induced by carbon tetrachloride, CCl$_4$. The hepatotoxin, CCl$_4$ in olive oil, was injected intraperitoneally into two groups of ICR mice which were made of 6 mice in each group. The control groups corresponding to the treated groups were prepared with the injections of olive oil only. After the injections, livers of two groups were extracted and measured biophoton emission in 24 hours and 72 hours later, respectively. We also extracted the plasma in the blood and measured the transaminase activity. Results show that biophoton emission from the livers in 24-hour treated group is 69.3${\pm}$21.2 counts/min/$\textrm{cm}^2$, which is two times more larger than that in 24-hour control group, 29.5${\pm}$5.9 counts/min/$\textrm{cm}^2$ Biophoton emission from the livers in 72-hour treated group is 37.0${\pm}$14.8 counts/min/$\textrm{cm}^2$. These biophoton results correlate with those of the biochemical assays. We conclude that biophoton emission can be used as a biomarker of mouse fatty liver induced by CCl$_4$.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.10
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• pp.1349-1355
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• 2006

This study was conducted to investigate the effect of methanol extract of Allomyrina dichotoma larva (MEAL) on carbon tetrachloride $(CCl_4)-induced$ hepatotoxicity in mice. ICR mice were divided into 5 groups [Vehicle control, $CCl_4\;(10{\mu}g/g)$ alone, $CCl_4$ plus a low dose $(50{\mu}g/g)$ of MEAL, $CCl_4$ plus a high dose $(100{\mu}g/g)$ of MEAL]. Silymarin $(2{\mu}g/g)$ was used as the reference in the experiment. Administration of MEAL tended to decrease the serum alanine transaminase (ALT) activity induced by $CCl_4$ treatment in mice. Hepatic concentration of thiobarbituric acid-reactive substances (TBARS) in a high-dose group of diet decreased to the level of silymarin-treated group. Hepatic activity of glutathione S-transferase in MEAL-treated group was lower than that of $CCl_4-treated$ group. Serum concentration of bilirubin was significantly increased by $CCl_4$ treatment, but MEAL or silymarin recovered the level. These results suggest that MEAL may exert the protective effect against $CCl_4-induced$ hepatotoxicity in mice. However, more intensive studies would be needed to elucidate the protective mechanism of the beetle on hepatotoxicity of mice.