• YAKHAK HOEJI
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• v.53 no.6
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• pp.314-320
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• 2009

We examined metabolic conversion of cysteine into glutathione (GSH) and taurine in rat liver under oxidative stress. Administration of tert-butylhydroperoxide (t-BHP) into the portal vein of male rats resulted in a rapid elevation of serum sorbitol dehydrogenase, alanine aminotransferase, and aspartate aminotransferase activities, which decreased gradually in 24 hr. Hepatic cysteine concentration was reduced in 3 hr, and recovered progressively, reaching a level greater than 200% of the normal value in 24 hr. GSH was increased both in liver and blood at 9 hr after t-BHP challenge, whereas hypotaurine or taurine was not altered. $\gamma$-Glutamylcysteine synthetase (GCS) activity was increased from 9 hr after t-BHP treatment, but protein expression of the GCS-heavy subunit was not changed in liver. Activity or expression of cysteine dioxygenase was not affected by t-BHP treatment. Taken together, these data show that an acute oxidant challenge to the rats may induce upregulation of cysteine availability and GCS activity, resulting in an enhancement of hepatic GSH synthesis, but the increased cysteine level does not stimulate taurine synthesis via cysteine sulfinate pathway. It is indicated that the regulation of GSH and taurine biosynthesis from cysteine is not solely dependent on the cysteine concentration in rat liver under oxidative stress.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.244-250
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• 1993

Hematotoxicity and vascular irritation of DA-125, a new anthracycline antitumor antibiotic, were investigated in mice and rabbits. In hematotoxicity study, healthy male ICR mice were treated with DA-125 by a single intravenous injection at doses of 18 and 24 mg/kg. After 4, 8, 12 and 16 days WBC count, RBC count, hemoglobin concentration, hematocrit value, and platelet counts were measured respectively. As a positive control, 12 mg/kg of doxorubicin (DXR) was used in the same manner. Remakable reductions of WBC counts in groups treated with DA-125 or DXR were observed 4 days after administration and returned to normal range 8 days after injection in groups of DA-125 18 mg/kg and DXR 12 mg/kg. The recovery of leukopenia induced in a group of DA-125 24 mg/kg took about 16 days after administration. The RBC counts, hemoglobin concentrations and hematocrit values also decreased in all drug treated groups on day 8 and recovered thereafter. The platelet counts of groups treated with DA-125 or DXR decreased on day 4 and recovered from day 8 of experiment. Local vascular irritation of DA-125 was also assessed in rabbits. The obtained results can be summarized as follows. 1. Thrombophlebitis was not induced even after daily intravenous administration of 0.4% solution of DA-125 or 0.2% solution of DXR for 7 days. 2. Macro- and microscopic observations revealed that the irritative activity of 0.4% solution of DA-125 in blood vessels was not so much different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 7 days. 3. Mild inflammatory reaction was noted around vessels in rabbits treated with 0.2% solution of DXR after consecutive intravenous infusion for more than 5 days. 4. The potencies of vascular irritation of the test solutions were summarized in the following order; saline = 0.4% DA-125<0.2% DXR. These results indicated that DA-125 showed similar pattern of hematotoxicity with DXR but was less hematotoxic than DXR, and that 0.4% solution of DA-125 did not elicit unusual toxic properties when injected through intravenous route for clinical practice.

• Korean Journal of Animal Reproduction
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• v.16 no.2
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• pp.103-107
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• 1992

The present study was conducted to find out the changes of progesterone levels in pre and post partum by the PGF2$\alpha$ administration to control artificial parturition in Korean native goats. A total of 24 goats were offered for this experiment. The animals were divided into 4 goats per treatment by the administration time(142, 145 or 148 day of pregnancy). Blood samples were taken from jagular vein pre-post partum by the PGF2$\alpha$ intramuscular administration. The progesterone in serum was assayed by radioimmunoassay. The serum progesterone level in late-pregnant goats averaged 4.85$\pm$0.55ng/ml, 4.05$\pm$0.47ng/ml or 2.76$\pm$0.25ng/ml on 142, 145 or 148 days of gestation. After the intramuscular injection with PGF2$\alpha$ for inducing parturition, it decreased remarkably to below 1.0ng/ml and to the base level(0.4~0.6ng/ml) at day 1 after parturition. And then this base level of progesterone was maintained until the final examination at 9 days of postpartum. No significant difference was found in the serum levels of progesterone between the doses treated for parturition induction. It was concluded that exogenous PGF2$\alpha$, administrated intramuscularly, induced premature parturition with causing withdrawal of progesterone levels for triggering luteolysis.

• Journal of Veterinary Science
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• v.25 no.4
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• pp.58.1-58.8
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• 2024

Importance: Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). Objective: This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). Methods: In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. Results: The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 ㎍/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). Conclusions and Relevance: These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.

• The Journal of Korean Medicine
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• v.20 no.3 s.39
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• pp.45-53
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• 1999

Since Radix Stemonae was recorded hypothennal and a little toxic in the 'Myngyubelrok (名醫別錄)', it has been recorded as having the same nature in many herbal books. However, the security of Radix Stemonae when used to treat respiratory disease over a long term has not been studied until now. Therefore, the objective of this study is to determine the effects of Radix Stemonae on the main organs if Radix Stemonae is administrated over a long term. In order to investigate the histological changes of the liver and kidneys of rats after oral administration of Radix Stemonae extract, the experimental rats were subdivided into control, 1, 3, 5, 7, 21, 28 and 35 days after administration groups, and 10 rats per group were used in this study. The control group was sufficiently supplied with water and solid forage. The other groups were administrated the reagent at 5mg/kg once a day by oral injection. Several times each day, the experimental groups were carefully observed for any changes of general condition, toxic symptoms, activity, appearance and the number of dead rats. The experimental groups were weighed and narcotized. For the histological observation, the tissues of liver and kidneys of the experimental groups were collected, stained by hematoxylin-eosin stain, and evaluated by observing the changes of gross appearance and by observing microscopic findings. 1. This drug, during the experimental term, did not induce any toxicological effect in mortality, abnormal symptoms or changes of body weight except for the 1 day after administration groups whose body weights were decreased, compared to the control group. 2. No gross changes of the liver and kidneys were observed in this study. 3. No histological changes of the liver were detected in 1 day after administration groups. However, dilation of the central vein was observed in 3, 5 and 7 days after administration groups and chronic passive congestion of the liver was demonstrated in the 21 days after administration groups. In the 28 and 35 days after administration groups, a centrolobular disposition of fatty tissue (adipose cell) was observed. 4. No histological changes of the kidneys were observed in this study. It is evaluated that if Radix Stemonae is administrated for a long term, it induces toxicity in the liver. So, to examine the toxicity of Radix Stemonae on the liver and kidney, it is necessary that the studies of biochemistry and electron microscopic findings about Radix Stemonae be systematically performed.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.17 no.10
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• pp.432-438
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• 2016

This study was conducted to investigate the effects of Lespedeza caneata extract on the livers of alcohol-administered mice. The study subjects were divided into a control (Con), alcohol administration (AL), alcohol and Lespedeza Caneata extract 200 mg/kg administration (AL-LC 200), and alcohol and Lespedeza caneata extract400 mg/kg administration (AL-LC 400) group. Distilled water was administrated orally to control and alcohol groups for ten days, while Lespedeza caneata extract was administered orally to alcohol and Lespedeza caneata extract groups for ten days. All experimental groups were fasted for twelve hours seven days after the oral administration, after which distilled water was administered orally to Con five times at twelve-hour intervals. At the same time, 50% ethanol (MERCK, USA) at 10 g/kg concentration was administered orally to AL and AL-LC groups five times at 12-hour intervals. The AST, ALT enzyme activation in blood and histology of the liver were then evaluated. AST and ALT in AL-LC groups were lower than in the AL group. Particularly, the AL-LC 200 and AL-LC 400 groups had significantly lower AST activation than the AL group. Histological results showed that most of the subjects in the AL group had necrosis and deformation in their livers, while fat droplets were accumulated in hepatic cells around the central vein. AL-LC 200 group revealed that a portion of the central vein was swollen, liver cells were expanded, and small fat droplets were accumulated. In the AL-CL 400 group, the central vein was normal and small fat droplets were accumulated in some liver cells. However, most of the liver cells appeared normal in the AL-CL 400 group. These results suggest that the extracts of Lespedeza caneata prevented alcohol induced liver damage in mice and have great potential for use as natural health products.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.67-77
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• 1993

Acute and chronic effects of ethanol (EOH) administration on the cardiovascular and hormonal responses to repeated hemorrhage were investigated in conscious normotensive Wistar rats and spontaneously hypertensive rats (SHR). The chronic EOH treated group received 5% EOH (vol/vol) ad libitum in the drinking water far the first week,10% for the last 2 weeks, and 20% for the last 5 weeks from the age of 6 weeks. The EOH free group received tap water. Chronic EOH and EOH free groups were randomly subdivided into acute EOH infusion and control groups. Under ether anesthesia, catheters were inserted into the femoral vein and both femoral arteries. After rats regained consciousness and their blood pressure was stabilized, responses to quick hemorrhage (5 ml/kg BW) were tested. In the acute EOH infusion group, hemorrhage was induced 20 min after EOH infusion (1.0 g/kg BW), Baroreceptor reflex sensitivity was assessed by the ratio of changes in hen.1 rate and mean arterial pressure (${\Delta}HR/{\Delta}MAP$) immediately after the hemorrhage. Chronic EOH administration elevated MAP in Wistar rats. During acute EOH infusion, MAP do- creased and HR increased in all groups. In comparison to EOH free control rats, acute or chronic EOH treated rats showed a greater reduction in MAP and a smaller elevation in heart rate in response to a hemorrhage. The degree of MAP reduction was significantly greater in SHR than in Wistar rats. Both the acute and chronic EOH administration attenuated the baroreceptor reflex and retarded MAP recovery, again the trend being much more prominent in SHR. The increase in plasma vasopressin and lenin concentrations after hemorrhage were intensified by the chronic EOH administration. SHR showed a greater vasopressin response but a smaller lenin response than Wistar rats. These results indicate that the EOH treated rats, particularly SHB, are prone to shock by a hemorrhage, which may be partly attributed to an impaired baroreceptor reflex function.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.114-133
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• 1998

In order to investigate the effects of Alcohol-Steamed Rhei Rhizoma and Row Rhei Rhizoma on varied extract time in both endotoxin-induced blood stasis model(hereafter Endotoxin Model) and hydrocortisone acetate-induced blood stasis model (hereafter HA Model), Half of rats were treated with endotoxin(0.4mg/kg, single Ⅳ, into caudal vein) for Endotoxin Model. Thereafter, they were orally administrated water extract of Alcohol-Steamed Rhei Rhizoma or Row Rhei Rhizoma, which were boiled during 30, 60, 120 minute, respectively. Finally, the number of platelet, fibrinogen, prothrombin time, hematocrit, the number of RBC and WBC were measured after sacrifice. The remainder rats were treated with hydrocortisone acetate(10mg/kg, daily IM for 7 days into the muscular rump) for HA significantly decreased. Together, they were orally administrated for 7 days water extract of Alcohol-Steamed Rhei Rhizoma or Row Rhei Rhizoma that were boiled above methods Finally, the number of platelet, fibrinogen, prothrombin time, hematocrit, the number of RBC and WBC were measured after sacrifice. The results were summarized as follows : 1. The number of platelet was significantly increased in boiled water extract for 30 min of Row Rhei Rhizoma group as compared with that of control group in Endotoxin Model. 2. Fibrinogen level was significantly increased in all administration groups as compared with that of control group in Endotoxin Model. It was significantly increased in all administration groups except boiled water extract for 30 min of Alcohol-Steamed Rhei Rhizoma group as compared with that of control group in HA Model. 3. Prothrombin time was significantly shortened in boiled water extract for 60 min of Alcohol-Steamed Rhei Rhizoma group and boiled water extract for 120 min of Alcohol-Steamed Rhei Rhizoma group as compared with that of control group in Endotoxin Model It was significantly shortened all administration groups as compared with that of control group in HA Model. 4 Hematocrit was significantly increased in all administered groups except boiled water extract for 60 min of Alcohol-Steamed Rhei Rhizoma group and boiled water extract for 30 min of Row Rhei Rhizoma group as compared with that of control group in Endotoxin Model. It was significantly increased in all administration groups as compared with that of control group in HA Model. 5. The number of RBC was significantly decreased in boiled water extract for 60 min of Alcohol-Steamed Rhei Rhizoma group, boiled water extract for 120 min of Alcohol -Steamed Rhei Rhizoma group and boiled water extract for 30 min of Row Rhei Rhizoma administered group in Endotoxin Model. It was significantly increased boiled water extract for 30 min of Row Rhei Rhizoma group and boiled water extract for 60 min of Row Rhei Rhizoma group in HA Model as compared with data of control group. 6 The number of WBC was significantly decreased in all administered groups except boiled water extract for 30 min of Alcohol-Steamed Rhei Rhizoma group and boiled water extract for 60 min of Alcohol-Steamed Rhei Rhizoma group as compared with that of control group in HA Model.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.265-271
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• 2001

In order to elucidate the influence of intestinal and hepatic first-pass effect on the pharmacokinetics of triflusal, the biotransformation of triflusal in the gastrointestinal tract and liver was designed. Moreover, we tried to establish an HPLC method applicable for bioassay and available to pharmacokinetics, not only with the simultaneous determination of triflusal and its active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), but also with improving sensitivity. After the administration of triflusal (10 mg/kg) and HTB (10 mg/kg) into femoral vein, portal vein (only triflusal) and oral route (only triflusal), pharmacokinetic parameters were investigated from the plasma concentration-time profiles of triflusal and HTB in rats. An HPLC method was developed for the simultaneous determination of triflusal and HTB in rat plasma, urine and bile. The HPLC analysis was carried out using a C18 column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The calibration curves were linear over the concentration range $0.05-5.0\;{\mu}g/ml$ for triflusal and $0.2-200.0\;{\mu}g/ml$ for HTB with correlation coefficients greater than 0.999 and with intra-day or inter-day coefficients of variation not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rats. It was supposed that triflusal was almost metabolized in vivo because urinary and biliary excreted amounts of triflusal could be ignored as it was lower than 1.2% of the administered dose. According to the gastrointestinal and hepatic biotransformation pathways of triflusal, it was found that triflusal was hydrolyzed by about 5% in intestine and metabolized by about 53% in liver, and that the bioavailability of triflusal after oral administration of triflusal was 0.44, and also that the fraction of total elimination rate of triflusal which formed HTB in liver $(F_{mi},\;%)$ was about 98%. These results showed that triflusal was almost metabolized in liver, and the total elimination of triflusal in the body was dependent to the formation rate of HTB from triflusal in liver.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.932-939
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• 2002

The aim of the present study was to determine the characteristics of cytisine on the secretion of catecholamines (CA) in isolated perfused rat adrenal glands, and to clarify its mechanism of action. The release of CA evoked by the continuous infusion of cytisine ($1.5{\times}10^{-5} M$) was time-dependently reduced from 15 min following the initiation of cytisine infusion. Furthermore, upon the repeated injection of cytisine ($5{\times}10^{-5}$), at 30 min intervals into an adrenal vein, the secretion of CA was rapidly decreased following the second injection. Tachyphylaxis to the release of CA was observed by the repeated administration of cytisine. The cytisine-induced secretion of CA was markedly inhibited by pretreatment with chlorisondamine, nicardipine, TMB-8, and the perfusion of $Ca^{2+}$-free Krebs solution, while it was not affected by pirenzepine or diphenhydramine. Moreover, the secretion of CA evoked by ACh was time-dependently inhibited by the prior perfusion of cytisine ($5{\times}10^{-6} M$). Taken together, these experimental data suggest that cytisine causes secretion of catecholamines from the perfused rat adrenal glands in a calcium-dependent fashion through the activation of neuronal nicotinic ACh receptors located in adrenomedullary chromaffin cells. It also seems that the cytisine-evoked release of catecholamine is not relevant to the activation of cholinergic M$_1$-muscarinic or histaminergic receptors.