• Toxicological Research
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• v.16 no.1
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• pp.73-76
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• 2000

Acute oral, intramuscluar, and intravenous toxicity studies of recombinant human interferon $\alpha$2$\alpha$(rhIFN $\alpha$2$\alpha$) were performed in Sprague-Dawley (SD) rats. SD rats were administered with doses of 31.25, 62.5, 125, 250 and 500 MIU/kg, respectively, and clinical signs, mortality and body weight changes were observed for 2 weeks. In all animals administered with rhIFN $\alpha$2$\alpha$, there was neither dead animals nor significant changes of body weights. In addition, no differences were found between control and treated groups in clinical signs and autopsy findings. Therefore, $LD_{50}$ of rhIFN $\alpha$2$\alpha$ was considered to be higher than 500 MIU/kg in SD rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.4
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• Journal of Veterinary Clinics
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• v.27 no.2
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• pp.163-169
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• 2010

To evaluate of oral toxicity of Epimedium koreanum nakai (EKN) water extract, three doses of EKN water extract (10, 100 and 1000 mg/kg/day) were administered to healthy Sprague-Dawley rats for 4 weeks. The results showed that there are no abnormal signs during the experimental period. The weights of testis and epididymis were increased dose-dependently, but seminal vesicle was decreased compared with control group. In hematology and serum chemistry, changes were observed within the normal ranges. In histological finding, slight to moderated changes were found but those were commonly or rarely encountered in the normal rats. These results suggest that no observed adverse effect level (NOAEL) of the oral application of EKN was considered to be more than 1000 mg/kg in SD rats under the conditions employed in this study.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.202-207
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• 2000

Background: Superior hypogastric plexus block has been advocated as a useful technique for the treatment of cancer related pelvic pain. The aim of this study was to evaluate the effect of neurolytic trans-intervertebrodiscal superior hypogastric plexus block for pelvic cancer pain. Methods: Twenty-eight patients with gynecologic, colorectal or genitourinary cancer who suffered intractable pain were studied. We performed superior hypogastric plexus block by trans-intervertebrodiscal approach at L5/S1 level under the C-arm fluoroscopic guide unilaterally or bilaterally. Ten ml of 100% dehydrated alcohol was injected through each needle. We evaluated the change of visual analog pain score (VAS; 0~100 mm) and daily dose of oral morphine sulphate at the time of pre-block and 7 days after the block. Results: Fourteen patients (50%) had satisfactory pain relief (VAS<30) while five patients (18%) had moderate pain control (VAS 30~60). The remaining nine patients (32%) had mild or little pain relief (VAS>60) and their daily oral morphine doses were above 160 mg. Additional pain control method may be needed for those patients who received high dose of opioid before neurolytic block. Conclusions: We conclude trans-intervertebrodiscal neurolytic superior hypogastric plexus block was effective in relieving pelvic cancer pain. Neurolytic block, earlier stage, may provide better effects for more comfortable life at the end stage for cancer patients.

• The Journal of Korean Medicine
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• v.32 no.6
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• pp.74-84
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• 2011

Objectives: Palmul-tang (hachimotsu-to in Japanese and bawu-tang in Chinese) is a mixture of eight herbs. It is traditionally used for the treatment of anemia, anorexia, general weakness, and female infertility in China, Japan, and Korea. In this study, we investigated the protective effects of Palmul-tang water extract (PTE) against ethanol-induced acute gastric injury in rats. Material and Methods: Acute gastric lesions were induced by intragastric administration of 5mL/kg body weight of absolute ethanol to each rat. Control group rats were given PBS orally and the ethanol group (EtOH group) received absolute ethanol (5mL/kg) by oral gavage. The positive control group and the PTE group were given oral doses of omeprazole (50mg/kg) or PTE (400mg/kg), respectively, 2 h prior to the administration of absolute ethanol. The stomach of each animal was excised and examined for gastric mucosal lesions. To confirm the protective effects of PTE, we evaluated the degree of lipid peroxidation, the level of reduced glutathione (GSH), and the activities of the antioxidant enzymes catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase in the stomach. Results: PTE reduced ethanol-induced hemorrhage and hyperemia in the gastric mucosa. PTE reduced the increase in lipid peroxidation associated with ethanol-induced acute gastric lesions and increased mucosal GSH content and the activities of antioxidant enzymes. Conclusion: These results indicate that PTE protects gastric mucosa against ethanol-induced acute gastric injury by increasing antioxidant status. We suggest that PTE could be developed as an effective drug for the treatment of acute gastric injury.

• CELLMED
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• v.5 no.1
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• pp.6.1-6.10
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• 2015

Fumaria indica Linn. (Syn: Fumaria parviflora, Fumariaceae) is a wildly grown weed, mentioned and recommended in classical Ayurvedic texts for treatments of variety of ailments including dermatological diseases, topical diseases, cardiovascular complaints, circulatory disease, fever and headache etc. The present pilot study was designed to experimentally verify the possibility that fumarates are the major bioactive principles of Fumaria indica extracts involved in their stress response modulating activities, and to estimate pharmacologicallyactive dose ranges of fumarates and standardized methanolic extract of Fumaria indica (MFI). Effect of single, 5 and 10 daily oral doses of pure fumaric acid (FA), monomethyl fumarate (MMF), dimethyl fumarate (DMF) and MFI was quantified in well validated rodent models viz. apomorphine induced cage climbing, stress induced hyperthermia, and elevated plus-maze tests. Obtained results reveal high efficacy of MFI and pure fumarates possess qualitatively analogous activity profiles in all the three tests. There were no significant difference in the potencies of pure FA, MMF and DMF in the three tests, whereas efficacy of MFI in the elevated plus maze test for anxiolytics was higher than in the other two tests. Efficacies of all the four test agents in all the three tests increased with increasing number of days of oral treatments. Results of these pilot experiments should be helpful for more rational selections of pharmacologically interesting dose ranges and treatment regimens of fumarates and Fumaria indica extracts for further more holistic explorations of their diverse therapeutic potentials.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.18 no.1
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• pp.177-187
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• 1988

This study was designed to investigate the effects of split irradiation on the salivary ductal cells, especially on the intercalated cells of the rat parotid glands. For this study, 24 Sprague-Dawley strain rats were irradiated on the head and neck region with two equal split doses of 9Gy for a 4 hours interval by Co-60 teletherapy unit, Picker's model 4M 60. The conditions of irradiation were that field size, dose rate, SSD and depth were 12×5㎝, 222 cGy/min, 50㎝ and 1㎝, respectively. The experimental animals were sacrificed 1. 2, 3, 6, 12, hours and 1, 3, 7, days after the irradiation and the changes of the irradiated intercalated cells of the parotid glands were examined under light and electron microscope. The results were as follows: 1. By the split irradiation, the degenerative changes of intercalated cells of the parotid glands appeared at 3 hours after irradiation and the most severe cellular degeneration observed at 6 hours after irradiation. The repair processes began from 12 hours after irradiation and have matured progressively. 2. Under electron microscope, loss of nuclear membrane, microvilli and secretory granules, derrangement of chromosomes, degeneration of cytoplasm, atrophy or reduction of intracytoplasmic organelles were observed in the intercalated ductal cells after split irradiation. 3. Under light microscope, derrangement of ductal cells, widening of cytoplasms and nuclei, hyperchromatism and proliferation of ductal cells were observed in intercalated ducts after split irradiation.

• Toxicological Research
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• v.28 no.1
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• pp.57-65
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• 2012

In this study, the 4-week oral toxicity and anti-cancer activity of the hexane layer of Melia azedarach L. var. japonica Makino's bark extract were investigated. We carried out a hollow fiber (HF) assay and 28-day repeated toxicity study to confirm the anti-cancer effect and safety of the hexane layer. The HF assay was carried out using an A549 human adenocarcinoma cell via intraperitoneal (IP) site with or without cisplatin. In the result, the 200 mg/kg b.w of hexane layer with 4 mg/kg b.w of cisplatin treated group, showed the highest cytotoxicity aginst A549 carcinoma cells. For the 28-day repeated toxicity study, 6 groups of 10 male and female mice were given by gavage 200, 100, or 50 mg/kg b.w hexane layer with or without 4 mg/kg b.w of cisplatin against body weight, and were then sacrificed for blood and tissue sampling. The subacute oral toxicity study in mice with doses of 200, 100, and 50 mg/kg b.w hexane layer showed no significant changes in body weight gain and general behavior. The cisplatin-treated group significantly decreased in body weight compared to the control group but regained weight with 100 and 200 mg/kg b.w of hexane layer. The biochemical analysis showed significant increase in several parameters (ALT, total billirubin, AST, creatinine, and BUN) in cisplatin-treated groups. However, in the group given a co-treatment of hexane layer (200 mg/kg b.w), levels of these parameters decreased. In hematological analysis, cisplatin induced the reduction of WBCs and neutrophils but co-treatment with hexane layer (100 and 200 mg/kg b.w) improved these toxicities caused by cisplatin. The histological profile of the livers showed eosinophilic cell foci in central vein and portal triad in cisplatin treated mice. These results show that hexane layer might have an anti-cancer activity and could improve the toxicity of cisplatin.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.19 no.3
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• pp.147-155
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• 2008

Objectives: The purpose of this study was to evaluate the efficacy and tolerability of osmotic release oral system-methylphenidate (OROS-MPH) in children with attention-deficit hyperactivity disorder (ADHD) and comorbid psychiatric disorders. Methods: This was an 8-week open label study of OROS-MPH monotherapy. The subjects were 113 children with ADHD aged 6-12 years. Outcome measures were the Korean version of the parent ADHD Rating Scale (K-ARS), Korean version of the Conners Parent Rating Scale (K-CPRS), Clinical Global Impression-Severity and Clinical Global Impression-Improvement. Side effects were monitored using Barkley's Side Effect Rating Scale. We compared the change-over-time in the mean scores of the outcome measure according to the comorbidity of disruptive behavior disorder, depressive disorder, anxiety disorder, and tic disorder. Results: The mean K-ARS and K-CPRS scores were significantly decreased, regardless of the comorbidity. The mean doses of OROS-MPH and dropout rate did not differ significantly according to comorbidity. The OROS-MPH was well tolerated, regardless of the comorbidity. However, children with tic disorder reported a higher frequency of tics or nervous movements between the $2^{nd}\;and\;8^{th}$ week than those without tic disorder. Conclusion: The OROS-MPH is effective for decreasing the symptoms of ADHD, and it is well tolerated, even by patients with comorbid psychiatric disorders.

• Toxicological Research
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• v.23 no.4
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• pp.363-371
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• 2007

Isaria sinelairii (IS) was orally administered at doses of 0, 0.04, 0.2, and 1 g/kg/day over a 13-week period. There were no observed clinical signs or deaths related to treatment in all the groups tested. Therefore, the approximate lethal oral dose of I. sinclairii was considered to be higher than 1 g/kg in rats. Throughout the administration periods, no significant changes in diet consumption, ophthalmologic findings, organ weight, clinical pathology (hematology, clinical chemistry, coagulation, and urinalysis) or gross pathology were detected. Minor changes were found in hematological parameters for the 0.04 g/kg/day and 0.2 g/kg/day IS treated groups (triglyceride reductions of $20.1{\sim}46.6%$ and platelet increases), but all changes were within physiological range. Microscopic examination failed to identify any treatment-related histopathologic changes in the organs of the IS-treated rats other than nuclear enlargement (cellular atypia) of the tubular regions in the medulla of the kidney in the high dose group. From these results, one can conclude that the no-observed effect level (NOAEL) of I. sinclairii is less than 0.04 g/kg/day in rats.