• Korean Journal of Veterinary Research
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• v.32 no.1
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• pp.35-39
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• 1992

SMZ is one of the most widely used antibacterial agents in veterinary medicine. It is also used as a growth promotant in many species of domestic animals There are marked species differences in its metabolism and pharmacokinetics. However, its pharmacokinetic and metabolism in rabbits. which are ragarded not only as good laboratorty animals hut also as good economical animals in its own, are lacking. Sex-differences in drug metabolism are well recognized in wide range of animal species including rats. Males are known to he more active than females. It is also know that there are Significant differences in the direction of metabolic pathways. But recently, female goats are reported to be more active in the metabolie capacity of SMZ than the other sex by Dutch researchers at Utrecht. Therefore, it is not easy to make general conclusicn of having higher SMZ metal-die capacity in the male compared to the opposite sex in every animal species. In this regard, the study on metabolic pattern of SMZ in rabbits, which are regarded as hervivorous, is of interest because the dietary habbits of rabbit are comparable to thai of goal, NEW Zealand White rabbits of each sex were given SMZ(35mg/kg) as a bolus injection into the marginalean, vein in order to study its pharmacokinetic profiles(using plasma) anc metabolic pattem(24h urine) as specified in the methods anc materials. 1. In the rabbit, the major metabolic pathway of SMZ was the acetylation(the formation of $N_4AcSMZ$). There were hydroxylation pathways(50HSMZ, $6CH_2OHSMZ$) as well, in the metabolism of SMZ in the rabbit, but minor pathways. 2. No sex differences in the metabolic direction of SMZ and its metabolites formation were found from the urinary excreted metabolites of SMZ out of 24h collected urine. 3. The concentration-time curves of SMZ(35mg/kg, iv) in the plasma compartment were fitted to a one-compartment open model when using a computer program(NONLIN). There was also no difference in the pharmacokinetic pattem of SMZ between two sexes. 4. The emergence of $N_4AcSMZ$ metabolized from SMZ was very fast in the plasma of the rabbit The elimination of $N_4AcSMZ$ was prolonged as compared to that of the parent drug Vie found no sex difference in the elimination pattern of $N_4AcSMZ$ in the rabbit.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.3
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• pp.868-873
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• 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 the East Asian Society of Dietary Life
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• v.15 no.1
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• pp.20-28
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• 2005

The dietary effect of water extracts of Liriopis tuber(WELT) in the diabetic SD-rats on the level of blood sugar and serum cholesterol was investigated. The experimental plots divided into normal group(N), diabetic control(DC), 5% WELT-group(WELT-I) and 10% WELT-group (WELT-II). Each group was fed for 6 weeks, then continuously fed for 1 more week after streptozotocin injection. The loss of the body weight fed for one week after induction of the diabetes was 2.2～6.3% in the WELT-I and -II groups, but it was 18.6% in the DC-group. There was no significant difference in the feed intakes after diabetes induction between N-group and WELT-group, while it was significantly increased in DC-group. The feed efficiency ratios before diabetes induction were 1.70 in WELT-I group, 1.53～1.59 in the N, DC and WELT-II group, while the ratios after diabetes induction were 0.92 in DC-group, 1.51～1.83 in the N, WELT-I and -II group. While the amounts of water intakes for one week after diabetes induction was 625.4 mL in the DC-group, and it were 364.3～371.1 mL in the WELT-groups showing no significant difference with N-group. The excretion amounts of urine were 431.96 mL in DC-group for one week after diabetes induction, and it was 182～192.84 mL in WELT-groups. The ratios of liver weight against body weight were 2.74% in N-group, 2.93～2.96% in WELT-groups, but it was 4.01% in DC-group. The level of blood glucose in WELT-groups fed for one week after diabetes induction were 136.8～138.6 mg/dL showing no significant difference with N-group, but it was 357.8 mg/dL in DC-group. The level of serum triacylglycerol and serum total cholesterol were 93.8 and 68.7 mg/dL in N-group, 120.1 and 101.6 mg/dL in DC-group, 97.4～100.6 and 60.8～67.7 mg/dL in WELT-groups, respectively, showing no significant difference between N-group and WELT-groups. HDL-cholesterol/total cholesterol ratio were 0.63 in N-group, 0.57～0.67 in WELT -groups, which was significantly higher than that of DC-group(p<0.05). Atherogenic index were 0.58 in N-group, 0.49～0.74 in WELT-groups, but it was 1.32 in DC-group. The above results suggest that the WELT diets may have both preventive and curing effects against the diabetes.

• Biomolecules & Therapeutics
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• v.5 no.3
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• The Korean Journal of Pesticide Science
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• v.14 no.4
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• pp.490-498
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• 2010

Isotianil is a fungicide which has prevention effects against rice blast disease. In order to register this new pesticide, the series of toxicity data on animal testing were reviewed to evaluate its hazards to consumers and to determine its acceptable daily intake. Isotianil was almost excreted by urine and feces. It has low acute oral toxicity while has no skin toxicity and ocular irritation. Its skin sensitization was evaluated as slight. Genotoxicity of parent compound and metabolite was negligible. Chronic toxicity tests on rats and dogs showed changes of hematology, clinical biochemistry and liver weight. It had no reproductive and teratogenic effects. The estimation of Acceptable Daily Intake(ADI) is based on the lowest no-observed adverse effect level (NOAEL). The lowest NOAEL of 2.83 mg/kg bw/day was found in the twelve-months rats study. The NOAEL was based on increased liver weight and treatment-related effect on clinica chemistry finding at the nest higher dose level of 2.83 mg/kg bw/day. Therefore, it is considered appropriated to apply an uncertainty factor of 100 to the NOAEL 2.83 mg/kg bw/day from the rat study, resulting in an ADI of 0.028 mg/kg bw/day.

• Toxicological Research
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• v.25 no.3
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• pp.140-146
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• 2009

This study was performed to evaluate the toxicity of cadmium selenide for a period of 28 days in Sprague-Dawley rats. Each of 10 healthy male and females rats per group received daily oral administration for 28-day period at dosage levels 30, 300 and 1,000 mg/kg of body weight. Mortality and clinical signs were checked, and body weight, water intake and food consumption were also recorded weekly. There were no dose-related changes in food consumption or urine volume. All animals survived to the end of study with no clinical signs or differences in body weight gain observed when compared with the control group. At the end of study, all animals including control group, were subjected to necropsy. Blood samples were collected for hematology tests including coagulation time and biochemistry analysis. Blood coagulation time and relative organ weight were unaffected by all received doses. White Blood Cell (WBC) counts significantly increased in the 300 mg/kg administered male animal group when compared to the control. Monocyte (MO) value were also increased significantly in both 300 and 1,000 mg/kg male animal group. However, Mean Corpuscular Volume (MCV) were significantly decreased compared with the control in the 1,000 mg/kg dose groups for male and female animals. Mean Corpuscular Hemoglobin (MCH) decreased significantly for female in the 300 and 1,000 mg/kg group compared to the control. Blood biochemical values of Inorganic phosphorus (IP) were significantly increased in both the 300 and 1,000 mg/kg dose groups in male animals when compared to the control. Creatinine (CRE) levels indicated significant increase in kidney function for the female, 30 mg/kg dose group when compared with control. There was a significant decrease in thymus absolute organ weight in the female, 1,000 mg/kg dose group when compared with control. Histopathological findings revealed no evidence of injury related to cadmium selenide except for one case of focal hepatic inflammation in the high dose (1,000 mg/kg) group. One case of lung inflammation was also seen in the control group. Basis on these result, the No Observable Adverse Effect Level (NOAEL) of cadmium selenide was determined to be more than 1,000 mg/kg/day for male and female rats under conditions in this study.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.7
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• pp.1119-1125
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• 2004

The effect of hemicellulose extracted from soy fiber on the level of blood glucose and serum cholesterol in the streptozotocin-induced diabetic rat were investigated. The experimental plots were divided to cellulose group (control, 0.5％ hemicellulose group (H-l) and 1％ hemicellulose group (H-2) group. The groups were fed for 6 weeks, then fed for 1 week more after streptozotocin injection. Food intakes, weight gain and food efficiency ratio of H-2 group were higher, while water intakes and liver weight were lower than those of control and H-l group. The content of blood glucose and urine glucose were 212.8 mg/dL, 0.97 mg/dL in the control group, 160.5 mg/dL, 0.53 mg/dL in the H-l group, 141.0 mg/dL, 0.35 mg/dL in the H-2 group, respectively. There was no significantly difference in the content of neutral lipid, while the content of total serum cholesterol was 101.6 mg/dL in the control group, 73.8-78.4 mg/dL in the hemicellulose groups. The content of serum HDL-cholesterol in the all experimental groups showed no significantly difference showing 39.8-44.7 mg/dL. HTR and atherogenic index were 0.44 and 1.27 in the control group, but 0.54 and 0.46-0.85 in the hemicellulose groups, respectively.

• Biomedical Science Letters
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• v.12 no.1
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• pp.23-27
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• 2006

The rate of metallothionein synthesis on cadmium-poisoned rats reflects the level of toxicity, and also it reduces the toxicity which is caused by the uptake of cadmium. Chlorella supplementation in the diets of the cadmium-poisoned rats decreased the concentration of cadmium in blood and urine compared with the control group. Although the liver and kidneys of rats are major target organs of cadmium and coherence of metallothionein and cadmium, no previous study has determined the correlation between the rate of metallothionein synthesis in the liver and kidneys of rats and dietary supplementation of chlorella with cadmium uptake. This study analyzed total metallothionein level on the tissue of the liver and kidneys, the concentration of cadmium bound to the metallothionein, and the total concentration of cadmium on the tissue of the liver and kidneys after dietary supplementation with 1%, 5%, and 10% dried chlorella and 40 ppm of cadmium to 46 male SD rats (mean weight: $150\pm20\;g$) for 4 weeks. According to the data analysis of the total rate of metallothionein synthesis in the liver and kidneys, the group of SD rats on the supplementation with 1% chlorella and 40 ppm of cadmium showed a rate of $93.2\pm8.9\;ng/g$, a significant decrease of 58.8% compared to that of the control group of SD rats on the supplementation with cadmium only, which showed a rate of $227.3\pm32.5 ng/g$ (P=0.0001). In contrast, no significant difference was observed through the changing of chlorella concentrations between 5% and 10% chlorella supplementation with cadmium. The group supplemented with 1% or greater chlorella levels represented a greater decrease in the total cadmium concentration of the kidney and liver tissues, the amount of total metallothionein synthesis, the amount of metallothionein with binding to cadmium, and the concentration of free cadmium without binding to metallothionein. Consequently, the supplementation of 1% and 5% chlorella was effective in reducing the synthesis of metallothionein for cadmium uptake, but increased the rate of binding of cadmium to metallothionein.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.474-483
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• 2004

To know the effects between Cd inhalation toxicity and extract of Radix Achyranthis Bidentatae, 4 rat groups were exposed to Cd aerosol in air using whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cd concentration in air was 1.03㎎/㎥ and mass median diameter(MMD) was 1.69㎛. 3 different dose intraperitoneal injections of extract of Radix Achyranthis Bidentatae to 3 inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were from inhalation exposure group I and the highest lung and liver weight were also from inhalation exposure group I. The highest kidney weight was from inhalation exposure group III. The lowest Cd content in lung was 33.49㎍/g from inhalation exposure group I. The lowest Cd concentration in blood was 9.36㎍/㎗ from inhalation exposure control. Cd concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. The lowest Cd concentration in liver was 21.08㎍/g from inhalation exposure group III and The lowest Cd concentration in kidney was 15.78㎍/g from inhalation exposure group II. For weekly Cd concentration in urine, the value of the fourth week from inhalation exposure group III was the highest. For weekly Cd concentration in feces, the value of the first week from inhalation exposure group III was the highest. The highest metallothionein concentration in lung was 53.42 ㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 188.18㎍/g from inhalation exposure group III. The highest metallothionein concentration in kidney was 143.92㎍/g from inhalation exposure group III. The highest Hct, Hb, and WBC values were from inhalation exposure group II and the highest RBC value was from inhalation exposure group III.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1243-1252
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• 2002

To experiment the effects between cadmium inhalation toxicity and extracts of Folium Mori, rat inhalation exposure groups were exposed to cadmium aerosol in air by whole-body inhalation exposure for 6 hours/day, 5 days/week, and 4 weeks. Cadmium concentration in the air of cadmium aerosol was 1.02㎎/㎥ and mass median diameter(MMD) was 1.40μm. Intraperitoneal injection of extracts of Folium Mori to inhalation exposure groups was done for 4 weeks and the results were as follows: The highest body weight gain for 4 weeks and food intake per day were 126.39g/4 weeks and 19.18g/day from inhalation exposure group III, respectively. The highest lung and liver weight were 1.27g and 8.19g from inhalation exposure group II, respectively. The highest kidney weight was 1.805g from inhalation exposure control. The lowest cadmium content in lung was 86.39μg/g from inhalation exposure group III. The lowest cadmium concentration in blood was 7.12㎍/㎗ from inhalation exposure group III. Cadmium concentrations of 40.02㎍/g in liver and 69.18㎍/g in kidney were the lowest from inhalation exposure group I and III, respectively. For weekly cadmium concentration in urine, the value of the fourth week from inhalation exposure group III was the highest, 3.12㎍/㎖. For weekly cadmium concentration in feces, the value of the fourth week from inhalation exposure group III was the highest, 2.67 ㎍/g. The highest metallothionein concentration in lung was 74.65㎍/g from inhalation exposure group III and the highest metallothionein concentration in liver was 386.84㎍/g from inhalation exposure group II. The highest metallothionein concentration in kidney was 236.17 ㎍/g from inhalation exposure group II.