• Journal of Life Science
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• v.28 no.5
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• pp.605-614
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• 2018

Bee pollen has an outer wall which is resistant to both acidic and basic solutions and even the digestive enzymes in the gastrointestinal tract. Therefore, the oral bioavailability of bee pollen is only 10-15%. A previous study reported on wet-grinding technology which increased the extraction of active ingredients from bee pollen by 11 times. This study was designed to investigate the safety of wet-ground bee pollen. First, a single dose of wet-ground bee pollen was tested in both rats and beagle dogs at dosages of 5, 10, and 20 g/kg and 1.5, 3, and 6 g/kg, respectively. In rats, compound-colored stools were found in those administered 10 g/kg or more of wet-ground bee pollen. In beagle dogs, 6 g/kg of wet-ground bee pollen induced diarrhea in one male for four hours. However, no obvious clinical signs were found through the end of the experiment in rats and beagle dogs. In addition, no histological abnormality was found in all animals. The data indicates that a single dose of up to 20 g/kg of wet-ground bee pollen is safe. Next, the genetic toxicity of nano-sized bee pollen was tested. This study employed a bacterial reverse mutation test, a micronucleus assay, and a chromosomal aberration assay. In the micronucleus assay, there was no genetic toxicity up to the dosage of 2 g/kg. There was also no genetic toxicity in the bacterial reverse mutation test and chromosomal aberration assay. This data provides important information in developing nano-sized bee pollen into more advanced functional foods and herbal medicines.

• Journal of Life Science
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• v.20 no.7
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• pp.969-976
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• 2010

In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

• Journal of Periodontal and Implant Science
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• v.38 no.sup2
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• pp.273-298
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• 2008

Purpose: The aim of this review is to introduce a novel bone-graft material for hard-tissue regeneration based on the calcium phosphate glass(CPG). Materials and Methods: CPG was synthesized by melting and subsequent quenching process in the system of CaO-$CaF_2-P_2O_5$-MgO-ZnO having a much lower Ca/P ratio than that of conventional calcium phosphates such as HA or TCP. The biodegradability and bioactivity were performed. Effects on the proliferation, calcification and mineralization of osteoblast-like cells were examined in vitro. Influence in new bone and cementum formations was investigated in vivo using calvarial defects of Sprague-Dawley rats as well as 1-wall intrabony defect of beagle dogs. The application to the tissue-engineered macroporous scaffold and in vitro and in vivo tests was explored. Results: The extent of dissolution decreased with increasing Ca/P ratio. Exposure to either simulated body fluid or fetal bovine serum caused precipitation on the surface. The calcification and mineralization of osteoblast-like cells were enhanced by CPG. CPG promoted new bone and cementum formation in the calvarial defect of Sprague-Dawley rats after 8 weeks. The macroporous scaffolds can be fabricated with $500{\sim}800{\mu}m$ of pore size and a three-dimensionally interconnected open pore system. The stem cells were seeded continuously proliferated in CPG scaffold. Extracellular matrix and the osteocalcin were observed at the $2^{nd}$ days and $4^{th}$ week. A significant difference in new bone and cementum formations was observed in vivo (p<0.05). Conclusion: The novel calcium phosphate glass may play an integral role as potential biomaterial for regeneration of new bone and cementum.

• Toxicological Research
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• v.35 no.2
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• pp.119-129
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• 2019

As the use of cosmetics has greatly increased in a daily life, safety issues with cosmetic ingredients have drawn an attention. Drometrizole [2-(2'-hydroxy-5'-methylphenyl)benzotriazole] is categorized as a sunscreen ingredient and is used in cosmetics and non-cosmetics as a UV light absorber. No significant toxicity has been observed in acute oral, inhalation, or dermal toxicity studies. In a 13-week oral toxicity study in beagle dogs, No observed adverse effect level (NOAEL) was determined as 31.75 mg/kg bw/day in males and 34.6 mg/kg bw/day in females, based on increased serum alanine aminotransferase activity. Although drometrizole was negative for skin sensitization in two Magnusson-Kligman maximization tests in guinea pigs, there were two case reports of consumers presenting with allergic contact dermatitis. Drometrizole showed no teratogenicity in reproductive and developmental toxicity studies in which rats and mice were treated for 6 to 15 days of the gestation period. Ames tests showed that drometrizole was not mutagenic. A long-term carcinogenicity study using mice and rats showed no significant carcinogenic effect. A nail product containing 0.03% drometrizole was nonirritating, non-sensitizing and non-photosensitizing in a test with 147 human subjects. For risk assessment, the NOAEL chosen was 31.75 mg/kg bw/day in a 13-week oral toxicity study. Systemic exposure dosages were 0.27228 mg/kg bw/day and 1.90598 mg/kg bw/day for 1% and 7% drometrizole in cosmetics, respectively. Risk characterization studies demonstrated that when cosmetic products contain 1.0% of drometrizole, the margin of safety was greater than 100. Based on the risk assessment data, the MFDS revised the regulatory concentration of drometrizole from 7% to 1% in 2015. Under current regulation, drometrizole is considered to be safe for use in cosmetics. If new toxicological data are obtained in the future, the risk assessment should be carried out to update the appropriate guidelines.

• Korean Journal of Clinical Pharmacy
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• v.22 no.2
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• pp.160-166
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• 2012

Purpose: The purpose of the present study was to investigate the pharmacokinetics of urea, a new potential diagnosis reagent of Helicobacter pylori infection. Methods: Considering the mechanism of urea breath test, we determined the excretion of urea in expired air after its oral administration in rats and beagle dogs at the dose of 2 mg/kg (including 50 mCi/mmol $^{14}C$-urea 50 ${\mu}Ci/kg$ for rats and 13.5 ${\mu}Ci/kg$ for dogs). Results: Urea was rapidly disappeared from the blood circulation by 1 hr after its i.v. bolus injection, followed by a slow disappearance by 24 hr. The half-lives at the distributive phase ($t_{1/2{\alpha}}$) and post-distributive phase ($t_{1/2{\beta}}$) were 2 min and 6 hr, respectively. The bioavailability of urea was 64.3% after its oral administration. The values of the volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) after the oral administration were compatible with those after i.v. administration. The recovery of urea in the bile was about 0.1% of the dose by 24 hr after its oral administration. Urea was extensively eliminated in the urine by 48 hr. The recovery ratios of urea in the urine and expired air were about 86.8% and 2.99% of the dose by 48 hr, respectively. Moreover, urea was mostly distributed from the blood circulation to the kidney, followed by being eliminated in the urine without metabolism. The concentration of urea in the kidney was 4.0 times higher than that of plasma at 40 min after its oral administration. Conclusions: These findings indicated that oral route appears to be available for the administration of urea. Orally administered urea, thus, was considered to be useful for the diagnosis of Helicobacter pylori infection.