• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.3
• /
• pp.868-873
• /
• 2004

Renal dysfunction could be developed as the secondary disease of liver cirrhosis. Delayed or suppresed lipid peroxidation by the treatment with physiological active substances could be explained as the antioxidative and protective effect in tissue damage. In this study, we investigated an antioxidative effect and renal function improvement of Hovenia dulcis in liver fibrosis(cirrhosis) induced rats. The female Sprague-Dawley rats (180∼210 g) were divided into 3 groups (Normal, AC: CCl₄ mixture treated group, AC-HV: CCl₄ mixture+ Hovenia dulcis treated group) and renal damage was developed by CCl₄ mixture administration in 4 weeks (0.8 ㎖/rat). The tissue of kidney and liver and sera were used for quantitative measurement of enzyme activity, MDA and Hyp. The histological change and gene expression of collagen α1(III) mRNA and a1(IV) mRNA were observed by Masson's trichrome staining and RT-PCR. As a result, the clinical biochemical parameters of liver function (AST and ALT) in sera of AC-HV group showed significantly 46.4% and 104.8% lower (p<0.005), and the level of ALP and BUN as the parameter of protein urine and azotemia showed 17.8 % and 25.8 % lower than in AC group. In AC-HV group, the concentration of MDA in kidney and liver was decreased significantly 15.8% and 21.3% when compared with AC group (p<0.01 -0.005). The content of Hyp in kidney of AC-HV group is merely higher than in AC group, in contrast to liver tissue. The expression of collagen α1(III) mRNA and collagen α1(IV) mRNA was decreased in AC, but both of collagen mRNA in normal and AC-HV group expressed fast similar. More massive lipid droplets, thicker collagen fiber bundles in portal triads and more formation of portal central septum were observed in the liver of AC group than in AC-HV group. In conclusion, CCl₄ mixture intoxication could be developed not only liver fibrosis(cirrhosis) but also renal dysfunction by the massive lipid peroxidation and suppression of interstitial collagen and basement membrane collagen synthesis. And the water extract of Hovenia dulcis may be possessed the antioxidative and protective effect and improvement of kidney function in renal dysfunction induced rats.

• Journal of Nutrition and Health
• /
• v.24 no.4
• /
• pp.337-343
• /
• 1991

The effect of 9-methyl folate on histidine oxidation, the uptake of an injected dose of $[^{3}H]folate$ by the livers and kidneys, the hepatic and blood folate levels were investigated by feeding crude x-methyl folate(XMF) at a level of 5 g per kg diet. 9-Methyl folate is konwn as a major forate antagonist in XMF to produce deficiency signs in rat. Feeding of XMF decreased histidine oxidation and hepatic folate levels significantly, which showed the function of 9-methyl folate as an antifolate in rats. The hepatic uptake of labeled folate in XMF- fed rats was decreased significantly. These data led to conclude that 9-methyl folate inhibited folate uptake and retention by tissue, especially liver, which could explain the low liver folate levels and the decreased histidine oxidation. However, only very low level of 9-methyl folate was detected in liver. It suggested that 9-methyl folate may be metabolized very quickly in the liver after uptaken.

• Toxicological Research
• /
• v.18 no.4
• /
• pp.331-339
• /
• 2002

Phenoxy compounds, 2,4-Dichlorophenol acetoxy acid (2,4-D) and 2,4-dichlorophenol (DCP), are widely used as a hormonal herbicide and intermediate for pesticide manufacturing, respectively. In order to assess the potential of these compounds as endocrine disruptors, we studied the androgenicity of them wing in vivo and in vitro androgenicity assay system. Administration of 2,4-D (50 mg/kg/day, p.o.) or DCP (100 mg/kg/day, p.o.) to rats caused an increase in the tissue weight of ventral prostate, Cowpers gland and glands penis. These increase of androgen-dependent tissues were additively potentiated when rats were simultaneously treated with low dose of testosterone (1 g/kg, s.c.). 2,4-D increased about 350% of the luciferase activity in the PC cells transiently cotransfected phAR and pMMTV-Luc at concentration of $10^{-9}$ M. In 2,4-D or DCP-treated castrated rats, testosterone 6$\beta$-hydroxylase activity was not significantly modulated even when rats were co-treated with testosterone. In vitro incubation of 2,4-D and DCP with microsomes at 50 $\mu$M inhibited testosterone 6$\beta$-hydroxylase activity about 27% and 66% in rat liver microsomes, about 44% and 54% in human liver microsomes and about 50% and 45% in recombinant CYP3A4 system, respectively. The amounts of total testosterone metabolites were reduced about 33% and 75% in rat liver microsomes, 69% and 73% in human liver microsomes and 54% and 64% in recombinant CYP3A4 by 2,4-D or DCP, respectively. Therefore, the additive androgenic effect of 2,4-D or DCP by the co-administration of the low dose of testosterone may be due to the increased plasma level of testosterone by inhibiting the cytochrome P450-mediated metabolism of testosterone. These results collectively suggested that 2,4-D and DCP may act as androgenic endocrine disrupter by binding to the androgen receptor as well as by inhibiting the metabolism of testosterone.

• Nutrition Research and Practice
• /
• v.10 no.1
• /
• pp.26-32
• /
• 2016

BACKGROUND/OBJECTIVES: It has been shown that vitamin A supplementation has different effects on skeletal health and the antioxidant system. Deficiency or excess of this vitamin can lead to health problems. Vitamin A can work as either an antioxidant or prooxidant depending on its concentration. The present study was conducted to investigate the effects of different doses of vitamin A supplementation on the antioxidant system in rats. MATERIALS/METHODS: Forty Spargue-Dawley male rats were divided into four groups according to the dose of vitamin A received: 0 (A0), 4,000 (A1), 8,000 (A2), and 20,000 (A3) IU retinyl palmitate/kg diet. After a feeding period of 4 wks, lipid peroxide levels, glutathione concentration, antioxidant enzyme activities, and vitamins A and E concentrations were measured. Histopathological changes were observed in rat liver tissue using an optical microscope and transmission electron microscope. RESULTS: Lipid peroxide levels in plasma were significantly decreased in the A1 and A2 groups compared to the A0 rats. Erythrocyte catalase and hepatic superoxide dismutase activities of the A2 group were significantly higher than those of the A0 group. Hepatic glutathione peroxidase activity was significantly lower in the A3 group compared to the other groups. Total glutathione concentrations were significantly higher in the A1 and A2 groups than in the A0 group. Histological examination of liver tissue showed that excessive supplementation of vitamin A might lead to lipid droplet accumulation and nuclear membrane deformation. CONCLUSIONS: These results indicate that appropriate supplementation of vitamin A might have a beneficial effect on the antioxidant system in rats.

• Journal of the Korean Society of Food Culture
• /
• v.5 no.2
• /
• pp.265-268
• /
• 1990

The effect of water extract in fruits of Omija (Schizandra chinensis Baillon) on alloxan-induced diabetic rats were determining the contents of metabolites and enzyme activities in the liver and serum of rat. The treatment with water extract in fruits of Omija showed increased in contents of protein, glycogen, and activity of glucose-6-phosphate dehydrogenase and a decreased in pyruvate content in the hepatic tissue from the alloxan treated group. These treatments were decreased contents of glucose, urea nitrogen, free fatty acid and activities of GPT, GOT, LDH.

• The Korea Journal of Herbology
• /
• v.22 no.2
• /
• pp.169-174
• /
• 2007

Objectives : This study was designed to investigate protective effects of Sayeoksanhap-Pyeongweisan-Gamiban(SPG) on hematological changes in rats damaged by CCl4 Methods : We investigated the effects of SPG on hematological changes in terms of AST/ALT levels, Total cholesterol, HDL-cholesterol and triglyceride in serum and lipid peroxidation in rat liver. Results : Administration of SPG decreased AST level in serum effectively. In addition, lipid peroxidation in liver tissue, which was elevated by injection of CCl4, was decreased by administration of SPG. In contrast, ALT level, Total cholesterol, HDL-cholesterol and triglyceride in serum were not affected by administration of SPG. Conclusion : These results suggest that oral administration of SPG was useful to protect liver against CCl4 by its antioxidant action in liver tissues.

• Biomedical Science Letters
• /
• v.7 no.3
• /
• pp.99-102
• /
• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1995.04a
• /
• pp.128-128
• /
• 1995

To investigate the mechanism of the regulation of cytochrome P450IA1 gene expression, ethoxyresorufin deethylase(EROD) and benzo(a)pyrene hydroxylase in B6 mouse liver, in isolated perfused rat liver system. and in B6 mouse hepatocyte Hepa-I cells were examined. In C57BL/6N mouse, 3-methylcholan- throne( 3MC ) treatment have resulted in the stimulation of EROD activity based on fluorometry by 2.79 fold comparirng with that of control. Measurement of mRNA of cytochrome P450 was carried out by either nothern blot or dot blot analysis. Findings are similar to that of studies with enzymes. Furhtermore, when RTPCR method was applied to detect mRNA in Hepa I cell and liver tissues the results were more clear. Cytochrome P450IA1 upstream DNA containing CAT construct was transfected into Hepa-1 cells. After transfection of CAT construct, 3MC and flavonoids, such as, chrysin, hesperetin, kaempferol, morin, myricetin and aminoyrine were treated. 48 Hours after treatments, cells were harvested and assayed for CAT mRNA by RTPCR. 3MC treatment to hepa I cells transfected with trout P450IA1-CAT construct increased CAT mRNA by 2.81 fold when it was compared with that of control. This increase CAT mRNA was decreased by concomitantly treated flavonoids and aminopyrine. The level of CAT protein was 29.2-58.0% of 3MC stimulated CAT protein. Results of this study suggested that RTPCR seems to be a very good method to study regulation of gene expression in liver tissue or Hepa cells.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.22 no.4
• /
• pp.863-870
• /
• 2008

The aim of this study was to investigate that Injinoryung-san-Ga-Samchilgun(IJORS) has an inhibitory effect on the development of liver fibrosis in rats. The influence of IJORS on liver stellate cell viability in rat was measured by the MTT assay, and proliferation was measured by the BrdU assay. The mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$, TIMP1, and TIMP2 all of which are associated with liver fibrosis, were analyzed by RT-PCR. The inhibitory effect of IJORS on procollagen production in hepatic stellate cell was examined using by enzyme immuno assay(procollagen Type 1 C-Peptide EIA). And after IJORS was orally administered to experimental rats with thioacetamide(TAA)-induced liver fibrosis for 4 weeks, the body weight, liver function test, complete blood and the change of portal pressure were measured. IJORS prevented hepatic stellate cell viability and proliferation in a dose-dependent manner. IJORS reduced the mRNA expression of procollagen type $1{\alpha}2$, ${\alpha}-SMA$ and TIMP1 and the production of procollagen protein. IJORS inhibited the increase of AST, ALT, WBC and portal pressure in rats administered by TAA. IJORS is considered to prevent liver fibrosis by inhibiting the activation of stellate cell and production of procollagen and prevent the progress of liver fibrosis by inhibiting the inflammation of liver tissue complicated in many liver disease.

• Biomedical Science Letters
• /
• v.11 no.4
• /
• pp.533-538
• /
• 2005

This investigation was performed to study the antioxidant activities of Hovenia dulcis THUNBER var. koreana Nakai fruits extracts and the effect of Hovenia dulcis fruits extracts on glucose, lipid metabolism in diabetic rats. DPPH free radical scavanging activitiy and superoxide anion radical Scavenging of Hovenia dulcis fruits $80\%$ methanol extracts were $0.06\pm0.002mg$ polyphrnol/ml and $0.l2\pm0.00lmg$ polyphmol/ml, respectively. Hovenia dulcis fruits $80\%$ methanol extracts were partitioned into hexan, dichloro methane, ethyl acetate and butanol, successively. Ethyl acetate fraction were good antioxidant activity. Streptozotocin (45 mg/kg body weight, i.p.) induced diabetic rats showed a significant increases of plasma glucose, triglyceride and total cholesterol. Concomitantly significant decrease of plasma high density lipoprotein. Glutathione level were decrease in cytosol of liver. Lipid peroxide were increase in microsome of liver. Group 1 and 2 were treated with Hovenia dulcis fruits ethyl acetate extracts 50 mg/kg body weight and 20mg/kg body weight for 24 days, individually. Group land 2 rats showed decreased plasma glucose, triglyceride, total cholesterol and lipide peroxide in microsome of liver tissue of rats, and increased plasma high density lipoprotein and glutathione in cytosol of liver tissue rats. The result suggest that Hovenia dulcis THUNBER var. koreana Nakai fruits extracts may effectively normalize the impaired antioxiants status in streptozotocin induced diabetic rats. Hovenia dulcis fruits ethyl acetate extracts were used to improve the imbalance between free radicals and antioxidant system due to the diabetes.