• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.39-40
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• 2003

Ochratoxin A (OA), a potent nephrotoxin in several species, is knownto be a renal carcinogen in animals and is implicated in the etiology of Balkan endemic nephropathy (BEN). The NTP (National Toxicology Program) classified Ochratoxin A as having clear evidence of carcinogenic activity, based on uncommon tubular adenomas and tubular cell carcinomas of the kidney and multiple fibroadenomas of the mammary gland, seen in the rat.(omitted)

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.285-291
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• 1999

DA-7101 is a new combined formulation of cefatrizine:clavulanic acid (2:1) under development as oral abtibiotics. The general pharmacological properties of DA-7101 on central nervous, cardiovascular, gas-trointestinal and other organ systems were studied by oral administration, in vivo and in vitro. DA-7101 had no marked effects all tests studied such as general behavior, hexobarbital-induced sleeping, spontaneous activity, anticonvulsion, body temperature, acetic acid-induced writhing, rotarod performance, heart rate and blood pressure in cats, isolated ileum movement, intestinal transition, gastric juice secretion and urine volume and electrolytes in rats. But exceptionally at the highest dose of 900 mg/kg, DA-7101 increased hexobarbital-induced sleeping time, caused a slight hypotension and decreased the secretion of gastric juice. These results suggest that at the estimated clinical dose DA-7101 would not bring about any serious acute adverse effects clinically.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.4
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• pp.563-569
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• 2013

This study was carried out to investigate the dose-response of chitooligosaccharide (with a molecular weight of 1~3 kDa) on antimicrobial activity and lipid lowering functions in rats. Sprague-Dawley male rats were given experimental diets containing 0 (control), 0.5, 2, or 5% chitooligosaccharide (COS) for 5 weeks. Weight gain and food intake were significantly lower in rats fed 5% COS than control rats and rats fed 0.5 and 2% COS. The numbers of fecal bacteria, including bifidobacteria, lactobacilli, bacteroides, total anaerobes, and total aerobes, which reflect gut microbiota, were significantly decreased in rats fed 5% COS. Plasma triglyceride concentrations significantly decreased in a dose-dependent manner in rats fed 2% or 5% COS, while plasma total cholesterol was not significantly different among groups. The hepatic concentration of triglycerides was lower in rats fed 5% COS, and fecal triglycerides significantly increased in rats fed 5% COS. These results indicate that 5% COS supplementation in a diet may exert antimicrobial activity in vivo, and inhibit the proliferation of typical gut microbes, while lowering lipids.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.202-202
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• 2002

• YAKHAK HOEJI
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• v.42 no.2
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• pp.205-213
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• 1998

The efficacy of DA-6034, a new flavonoid derivative, was investigated in comparison with sulfasalazine in a trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. Under light anaesthesia with ether, rats were subjected to intracolonic administration of 30mg TNBS in 50% ethanol (0.5ml) and were then sacrificed at 7 or 21 days after colitis induction. The TNBS control group (the saline treated colitic rat) exhibited ulceration and inflammation of the distal colon with formation of granuloma and pathologic connections. Moreover, an increase in colonic myeloperoxidase (MPO) activity (investigated as an index of leukocyte adhesion and accumulation) and an elevated colonic leukotriene $B_4$ ($LTB_4$) level were observed. The colitic rats received DA6034 (0.3-30mg/kg) or sulfasalazine (50-100mg/kg), prednisolone (0.3-3mg/kg) after the induction of colitis until they were sacrificed. Oral treatment with DA-6034 resulted in significant reductions of macroscopic colonic damage, colonic inflammation. DA6034 had a more potent effect than sulfasalazine and prednisolone on macroscopic colonic damage, while it has similar effect with prednisolone on the reduction of colonic $LTB_4$ synthesis and MPO activity. This study show, therefore, that DA-6034 is effective m attenuating the colonic lesion in an TNBS-induced colitis model. Furthermore, the results suggest that the effect of DA-6034 is partially related to its action on $LTB_4$ synthesis and MPO inhibition.

• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.181-189
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• 2013

Motilitone$^{(R)}$ (DA-9701) is a new herbal drug that was launched for the treatment of functional dyspepsia in December 2011 in Korea. The heterogeneous symptom pattern and multiple causes of functional dyspepsia have resulted in multiple drug target strategies for its treatment. DA-9701, a compound consisting of a combination of Corydalis Tuber and Pharbitidis Semen, has being developed for treatment of functional dyspepsia. It has multiple mechanisms of action such as fundus relaxation, visceral analgesia, and prokinetic effects. Furthermore, it was found to significantly enhance meal-induced gastric accommodation and increase gastric compliance in dogs. DA-9701 also showed an analgesic effect in rats with colorectal distension induced visceral hypersensitivity and an antinociceptive effect in beagle dogs with gastric distension-induced nociception. The pharmacological effects of DA-9701 also include conventional effects, such as enhanced gastric emptying and gastrointestinal transit. The safety profile of DA-9701 is also preferable to that of other treatments.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• Journal of Life Science
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• v.25 no.7
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• pp.765-772
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• 2015

The aim of this study was to determine the effect of decursin (D) and decursinol angelate (DA) against bisphenol A (BPA) toxicity in a rat two-generation study. Adult rats were divided into the following three groups: (1) control, (2) BPA, and (3) BPA+D/DA. The D and DA treatment of F0 parents increased the terminal body weight and relative adult organ weights (testes, kidneys, spleen, and liver) when compared with the BPA group. A significant decrease in sperm count was found in the BPA+D/DA (7.69%) and BPA (64.70%, p<0.01) groups, when compared with the sperm count in the control group. No offspring were obtained in the F1 generation of the BPA (50 mg/kg/day) group, but the addition of D/DA in the BPA+D/DA group significantly restored fertility (55.78%) and gestation indices (98.87%) in the F1 generation. No significant differences were found in the fertility index between the control (75.02%) and the BPA+D/DA (78.11%) groups in the two-generation study, when compared with the one-generation study. The viability ratio during lactation in the D/DA group was also similar to that of the control group. These data indicate that D/DA (50 mg/kg/day) administered over two generations causes significant positive changes in reproductive or developmental parameters.

• Journal of Ginseng Research
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• v.17 no.3
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• pp.187-195
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• 1993

We have examined the functional role of central dopaminergic processes on the behavioral pharmacological effects induced by psychotropics and red ginseng saponins of normal rats and compared with that of brain damaged rats. Desipramine and clomipramine produced, a significant depression of the locomotor activity in normal rats, but in brain damaged rats, they did not have any effect throughout the experimental period of 4 hours. Total saponin (50~200 mg/kg), PT (25~50 mg/kg), PD (25~50 mg/kg), $Rg_1$(12.5~25 mg/kg), $Rb_1$ (12.5~50 mg/kg) did not change, and high concentrations of PT (100 mg/kg), PD (100 mg/kg) and $Rg_1$ (50 mg/kg) showed a significant decrease in the locomotor activity of one hour after administration but total saponin (100 mg/kg), PD (25~50 mg/kg), Rgl (12.5 mg/kg), $Rb_1$ (12.5 mg/kg) markedly increased the locomotor activity of four hour after administration in normal rats. On the other hand, total saponin (50 mg/kg), PT (100 mg/kg) and PD (100 mg/kg) Produced a prominent stimulation of the locomotor activity in brain damaged rats. These results suggest that the inhibition of the locomotor activity induced by antidepressants was not affected by the sensitivity of cerebral DA system, whereas red ginseng saponin showed antifatigue effect and also the stimulation of the locomotor activity induced by red ginseng saponin was mediated by the inhibition of cerebral DA system. These psychotropic action of red ginseng saponins could be responsible for the beneficial effects on conditions of fatigue and decreased alertness.

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.390-396
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• 2011

Background: Hyaluronan (HA) is an unbranched glycosaminoglycan. It has been proposed that HA acts as a vehicle for cytokines due to the strong negative charge on its surface. We hypothesized that HA would function like a cytokine scavenger and reduce the inflammatory signaling cascade and this would lead to improved survival in rats suffering with endotoxemia. Methods: Endotoxin (Salmonella, 10 mg/kg) or an equal amount of 0.9% NaCl (NS) was injected into the jugular vein of rats. HA (1,600 kDa, 0.35%) or NS was given at 0.1 mL/kg/h for 3 hours. HA or NS infusion was started at 4 hour after endotoxin injection. The rats were divided into the control and HA groups (n=16 for each group). The mean arterial pressure (MAP) was monitored during HA or normal saline infusion. Survival was assessed every 12 hours for 3 days throughout the experiment. Results: The survival rate (%) of the rats treated with HA was higher (60%) than that of the controls (20%) when HA was infused 4 hours after lipopolysaccharide (LPS) injection. The bronchoalveolar lavage (BAL) fluid of the animals surviving HA or NS infusion 4 hours after LPS showed that the total cell counts and number of neutrophils were significantly (p < 0.01) reduced in the HA treated groups compared with that of the controls (total cell count, $9.2{\times}10^4$/mL vs. $61{\times}10^4$/mL; neutrophils, $21{\times}10^4$/mL vs. $0.2{\times}10^4$/mL, respectively). There was no significant MAP difference between the HA or control groups either with or without endotoxin. Conclusion: Infusion of hyaluronan (1,600 kDa) reduced the BAL total cell count and the number of neutrophils and it improved the survival rate of the endotoxemic rats.