• Archives of Pharmacal Research
• /
• v.26 no.1
• /
• pp.47-52
• /
• 2003

The aim of this study was to investigate the effects of trauma on alterations in cytochrome P450 (CYP 450)-dependent drug metabolizing function and to determine the role of Kupffer cells in hepatocellular dysfunction. Rats underwent closed femur fracture (FFx) with associated soft-tissue injury under anesthesia, while control animals received only anesthesia. To deplete Kupffer cells in vivo, gadolinium chloride (GdCl$_3$) was injected intravenously via the tail vein at 7.5 mg/kg body wt., 1 and 2 days prior to FFx surgery. At 72 h after FFx, serum alanine aminotransferase (ALT) activity was increased, and this increase was attenuated by GdCl$_3$ pretreatment. Serum aspartate aminotransferase (AST) and lipid peroxidation levels were not changed by FFx. Hepatic microsomal CYP 450 content and aniline p-hydroxylase (CYP 2E1) activity were significantly decreased; decreases that were not prevented by GdC1$_3$. The level of CYP 2B1 activity was decreased by Kupffer cell inactivation, but not by FFx. There were no significant differences in the activities of CYP 1A1, CYP 1A2 and NADPH-CYP 450 reductase among any of the experimental groups. Our findings suggest that FFx trauma causes mild alterations of hepatic CYP 450-dependent drug metabolism, and that Kupffer cells are not essential for the initiation of such injury.

• Korean Journal of Pharmacognosy
• /
• v.28 no.4
• /
• pp.280-285
• /
• 1997

Pectenotoxin 2 (PTX2), isolated from marine sponges, was examined for its hepatotoxic potential using male ICR mice. PTX2 $(20\;or\;100\;{\mu}g/kg/day,\;ip)$ was administered to mice repeatedly for one or two week. Histopathological examination revealed an increase in granularity in the liver from the mice treated with PTX2. PTX2 did not alter the parameters for hepatotoxicity and nephrotoxicity such as sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and blood urea nitrogen (BUN). Cytochrome P-450, cytochrome $b_5$, or NADPH cytochrome c reductase was net changed by repeated administration of PTX2. Hepatic microsomal activity of p-nitroanisole O-demethylase, but not aminopyrine N-demethylase, was slightly depressed by PTX2 administerd repeatedly $(100\;{\mu}g/kg/day,\;ip)$ fur 2 weeks. The toxicity of PTX2 $(200\;{\mu}g/kg/day,\;ip)$ was determined in mice pretreated with a metabolic inducer or inhibitor such as phenobarbital, 3-methyl-cholanthrene, $CoCl_2$, or SKF 525-A. Significant alterations in lethality and hepatotoxicity of PTX2 were observed in mice pretreated with a metabolic modulator. The results suggest that liver seems to be the target organ for PTX2 toxicity and also that induction of the PTX2 toxicity may be associated with hepatic drug metabolizing activity.

• Parasites, Hosts and Diseases
• /
• v.59 no.3
• /
• pp.297-301
• /
• 2021

Toxoplasma gondii infection is widespread worldwide, not only posing a serious threat to human food safety and animal husbandry, but also endangering human health. The selectivity index was employed to measure anti-T. gondii activity. Hederagenin (HE) exhibited potent anti-T. gondii activity and low cytotoxicity. For this reason, HE was selected for in vivo experiments. HE showed 64.8%±13.1% inhibition for peritoneal tachyzoites in mice, higher than spiramycin 56.8%±6.0%. Biochemical parameters such as alanine aminotransferase, aspartate aminotransferase, glutathione, and malondialdehyde, illustrated that HE was a good inhibitor of T. gondii in vivo. This compound was also effective in relieving T. gondii-induced liver damage. Collectively, it was demonstrated that HE had potential as an anti-T. gondii agent.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.36 no.3
• /
• pp.291-297
• /
• 2007

This study was conducted to investigate the hepatic detoxification effect of microcluster-water (McW). Animal experiments were divided into 4 groups: distilled water intake group (DC), distilled water intake-bromobenzene treated group (DB), McW intake group (MC), and McW intake-bromobenzene treated group (MB). There were no significant differences in alanine aminotransferase and aspartate aminotransferase activities between DC and MC groups, but the activities in MB group were significantly (p<0.05) lower than those in DB group. No apparent changes of aniline hydrolase activity were shown in all experimental groups, while glutathione S-transferase activity in MC and MB groups was higher than that in DC and DB, respectively. The content of hepatic lipid peroxide in DC group was similar to that of MC group. In addition, the contents in DB and MB groups were significantly (p<0.05) increased than that of DC group. The increasing rate in MB group was lower than that of DB group. Also, the electron donating activity of McW was significantly (p<0.05) higher than that of distilled water. From these results, it could be suggested that McW has the possibility of having detoxification effect of bromobenzene induced hepatic injury by increasing glutathione S-transferase, which is known as a kind of hepatiic detoxification enzyme.

• Toxicological Research
• /
• v.3 no.2
• /
• pp.73-80
• /
• 1987

Primary cultures of adult rat hepatocytes were used to study the cytotoxicity of D-galactosamine. Hepatocytes were isolated by a collagenase perfusion technique and maintained as monolayers in serum-free medium on collagen-coated culture dishes. Treatment of galactosamine to the culture markedly inhibited the uptake of ${\alpha}$-aminoisobutyric acid (AIB) inducible with glucagon and dexamethasone. At0.1 mM of galactosamine, AIB uptake was inhibited significantly when treated for 12 hr. At higher doses (0.25, 0.5 and 1.0mM), a significant inhibition was noticed after 1 hr exposure. Generally the magnitude of the inhibition was related to the dose and treatment time of galactosamine. Treatment of galactosamine also produced a dose- and treatment time-related suppression of the tyrosine aminotransferase (TAT) induction caused by dexamethasone. Meanwhile, uptake of ouabain was not affected by the treatment of galactosamine. The viability of the hepatocytes was decreased only slightly by the treatment of galactosamine; more than 87% of the cells excluded tryphane blue when treated 1 mM galactosamine for 12 hr. Galactosamine induced depressions of AIB uptake and TAT activity were prevented by the simultaneous addition of uridine to the culture. D-Galactosamine, cytotoxicity, hepatocytes culture, ${\alpha}$-aminoisobutyric acid uptake, tyrosine aminotransferase.

• Nutritional Sciences
• /
• v.6 no.2
• /
• pp.85-93
• /
• 2003

The purpose of this study was to investigate the effects of a butanol fraction of fraction of Alisma canaliculatum All. Braun et Bouche (Ac), and of selenium (Se), on plasma gllucose and lipid levee in streptozotocin (STD-induced diabetic rats. Male Sprague-Dawley rats, fed the AIN-93 recommended diet, were divided into five groups: a non-diabetic control group (no STZ treatment), and four 572-induced diabetic groups which consisted of a diabetic-control group, an Ac-treated group, an Ac-Se treated group, and a Se-treated group. Diabetes was induced in the rats by an injection of STZ into the tail vein at a dose of 45 mg/kg body weight. The butanol (BuOH) fraction of Ac was orally administered at a rate of 400 mg/kg body weight for 21 days to both the Ac and Ac-Se groups. The supplementation of selenium in the Se and Ac-Se groups was achieved by adding (freshly, every day) 2 mg of Se as Na$_2$SeO$_3$ per kg of feed. The rats'body weights and hematocrit (Hct) levels were measured, along with plasma levels of glucose, insulin, cholesterol, HDL-cholesterol, triglyceride (TG), and free fatty acids (FFA). Aminotransferase activities were also analyzed. The non-diabetic rats gained weight, while the diabetic rats lost weight - except in the Ac-Se group, which maintained their initial weight. The blood glucose levels of the Ac group and the Se group were significantly lower than for the diabetic-control group. The plasma triglyceride levels were lowered when both Ac and Se were administered to diabetic rats. The concentrations of plasma FFA in the Ac-Se group were significantly lower compared with the diabetic-control group. Plasma cholesterol levels and alanine aminotransferase activity in the Ac, Ac-Se, and Se groups were significantly lower when compared with the diabetic-control group. Aspartate aminotransferase activity was significantly lower in the Se group compared to the other diabetic groups. These data show that treatment with a butanol fraction of Ac in combination with Se has no synergistic effect. Plasma glucose levels tended to be low when Se was administered to diabetic rats. Supplementation of Se in diabetic rats did not elicit a significant increase in plasma insulin levels or result in hypolipemic effects.

• Korean journal of food and cookery science
• /
• v.18 no.3
• /
• pp.300-308
• /
• 2002

The purpose of this study was to investigate the effect of chloroform(CHC1$_3$) fraction of Alisma canaliculatum All. Braun et Bouche(Ac) with selenium(Se) on the plasma glucose and lipid levels in streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into five groups. The normal and diabetic rats were separated into four groups: the STZ-control group, the Ac group, the Ac-Se group and the Se group. Diabetes was induced in the male rats by an injection of STZ into the tail vein at a dose of 45 mg/kg. The CHCl$_3$fraction of Ac(250 mg/kg) was administered orally for 14 days. The supplementation was achieved with the AIN-93 recommended diet by adding 2 mg/kg diet of selenium as Na$_2$SeO$_3$. which was prepared freshly everyday. The body weight, hematocrit(Hct), glucose, insulin, cholesterol, HDL-cholesterol, triglyceride(TG) and free fatty acids(FFA) concentrations in plasma were measured. The aminotransferase activities were also analyzed. The changes of body weight in the experimental groups were not significantly different from that of the STZ-control group, but diabetes hyperphagia accompanied changes with body weight loss in Ac-Se group. The levels of Plasma cholesterol were not significantly different among the experimental groups. The concentrations of FFA in the Ac-Se group increased significantly compared with the STZ-control group. The effect of Se alone significantly increased aspartate aminotransferase activity and alanine aminotransferase activity. The results showed that the treatment of CHCl$_3$fraction of Ac in combination with Se has no synergistic effect. There was a tendency for the plasma glucose levels to decrease when Se was administered into diabetic rats. Supplementation of Se in diabetic rats did not elicit a significant increase in plasma insulin levels and exhibited hypotriglyceridemic effect.

• Journal of Microbiology and Biotechnology
• /
• v.24 no.7
• /
• pp.998-1003
• /
• 2014

Aspartate aminotransferase (AST; E.C. 2.6.1.1), a vitamin B6-dependent enzyme, preferentially promotes the mutual transformation of aspartate and ${\alpha}$-ketoglutarate to oxaloacetate and glutamate. It plays a key role in amino acid metabolism and has been widely recommended as a biomarker of liver and heart damage. Our study aimed to evaluate the extensive preparation of AST and its application in quality control in clinical laboratories. We describe a scheme to express and purify the 6His-AST fusion protein. An optimized sequence coding AST was synthesized and transformed into Escherichia coli BL21 (DE3) strain for protein expression. Ideally, the fusion protein has a volumetric productivity achieving 900 mg/l cultures. After affinity chromatography, the enzyme activity of purified AST reached 150,000 U/L. Commutability assessment between the engineered AST and standard AST from Roche suggested that the engineered AST was the better candidate for the reference material. Moreover, the AST showed high stability during long-term storage at $-20^{\circ}C$. In conclusion, the highly soluble 6His-tagged AST can become a convenient tool for supplying a much better and cheaper standard or reference material for the clinical laboratory.

• Korean Journal of Medicinal Crop Science
• /
• v.7 no.2
• /
• pp.107-114
• /
• 1999

It has long been recognized that dropwort contains specific funtional subtances for protecting human liver and preventing and curing its diseases, and thus it has been widely utilized in traditional folk remedy. In the present study. fresh of fermented extract of dropwort shoots grown on dryland and fresh extract of those grown on flooded fie1d were fed to the rats suffering from acute, subacute or chronical toxication induced by alcohol administration, and their affects were investigated. Administration of alcohol to rats and mice for 2 days at 5ml of 30% EtOH/kg/day raised total cholesterol and total glyceride which were, however, great1y supressed when alcohol was administered to the laboratory animals previously fed on fresh or fermented extract of dryland dropwort, or fresh extract of flooded field-grown dropwort for 20 days, without significant differences among the extracts. The levels of alanine aminotransferase and aspartate aminotransferase which were raised by alcohol adminstration were also lowered by feeding dropwort extract, among which that of fermented dryland-grown one was more effective than the other two. Chronic alcohol toxication was induced to rats by administering 10% alcohol for 10 months and fermented dropwort extract or tap water was fed to the rats for 5 days. The rats fed on fermented dropwort extract were lower in total cholesterol by 40% and in tota1 glyceride by 60% than the control. Alanine aminotransferase and aspartate aminotransferase in the rats fed on fermented dropwort extract were decreased by 87.2% and 91.7%, respectively, compared to the control, and the rats recovered almost to normal. Activity of alkaline phosphatase, catalase, superoxide dismutase or glutathione peroxidase changed greatly by alcohol administration in the rats suffering from chronic as well as acute toxication. The extract of fermented dry land dropwort significantly lowed the activity of those enzymes, especially, alkaline phosphatase and superoxide dismutase. The present results suggesting the possible medicinal effect of fermented dropwort extract to liver diseases.

• Toxicological Research
• /
• v.11 no.2
• /
• pp.279-288
• /
• 1995

To apply the serum xanthine oxidase (XO) determining for the index of the toluene intoxication, the serum XO activity was compared with the other parameters, the activities of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), 5'-nucleotidase(5'-NT), alkaline phosphatase(ALP), guanase(GDA) and $\gamma$-gIutamyl transpeptidase(T-GTP). Concomitantly, the cause of increased level of serum XO was clarified in the present experimental conditions. Although the other serum enzyme activities, ALT, AST, 5'-NT, ALP, GDA and $\gamma$-GTP were respectively not found to be different between control group and toluene-treated group, the serum XO activity in toluene-treated group showed the higher levels than that in the control group. These suggested that the determination of serum XO activity could be used for monitoring the intoxication of toluene. On the other hand, the activities of XO both in the serum and liver were higher in toluene-treated or benzaldehyde-treated rats than those in each control group. In the pooled liver XO from each group, toluene-treated or benzaldehyde-treated group showed the higher $V_{max}$ value than the control group, whereas no changes were observed in liver XO activities between the control liver specimen and that preincubated with bertzaldehyde in vitro. The present results indicate that the increased level of XO in toluene-treated rats is due to the result of enzyme protein induction in liver cell by the benzaldehyde metabolized from toluene. All the more, the benzaldehyde may be acted as a substrate for XO, since the benzaldehyde induced the increased activity of both liver and serum XO, and no changes were found in purine catabolite, uric acid in serum or urine and liver purine catabolizing enzymes, adenosine deaminase, GDA, uricuse except XO in toluene-treated rats.