• Archives of Pharmacal Research
• /
• v.24 no.4
• /
• pp.323-326
• /
• 2001

Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

• Food Science of Animal Resources
• /
• v.42 no.4
• /
• pp.609-624
• /
• 2022

Tenebrio molitor larvae, as known as edible insects, has advantages of being rich in protein, and has been recognized as a suitable alternate protein source for broiler and pig feed. Moreover, given their ability to biodegrade polystyrene, a major pollutant, Tenebrio molitor larvae has been proposed as an innovative solution to environmental problems. In the present study, we investigated the toxicity of Tenebrio molitor larvae powder (TMlp) ingested with expanded-polystyrene (W/ eps) through in vitro and in vivo experiments. The objective of this study was to determine whether TMlp W/ eps can be applied as livestock alternative protein source. For in vitro experiments, cytotoxicity test was performed to investigate the effects of TMlp-extract on the viability of estrogen-dependent MCF-7 cells. The possibility of estrogen response was investigated in two groups: Expanded-polystyrene-fed (W/ eps) TMlp group and without expanded-polystyrene-fed (W/o eps) TMlp group. For in vivo experiments, The male Sprague-Dawley rats were divided based on the dosage of TMlp administered and oral administration was performed to every day for 5 weeks. A toxicological assessments were performed, which included clinical signs, food consumption, body and organ weights, hematology, serum chemistry, and hematoxylin and eosin staining of liver and kidney. There were no specific adverse effect of TMlp W/ eps-related findings under the experimental conditions of this study, but further studies on both sexes and animal species differences should be investigated. In conclusion, TMlp W/ eps was considered non-toxic and observed to be applicable as an alternative protein source for livestock feed.

• Journal of Environmental Health Sciences
• /
• v.47 no.1
• /
• pp.1-19
• /
• 2021

Objectives: Phthalates, which are widely used as plasticizers, have been recognized as endocrine disruptors. In the present study, we provided information on the regulation of these chemicals and summarized the information available on their detection and toxicity in children's products and those of their alternatives. Methods: The regulatory frameworks related to phthalates in children's products in Korea, the United States (US), and the European Union (EU) were compared. Data on the detection concentration of 16 phthalates and seven phthalate alternatives that could be used in polyvinyl chloride (PVC) plastic products for children as well as on their toxicity classification and endocrine disruption toxicity were collected from the literature. Results: Korea adopted US and EU chemical standards for six phthalates (DEHP, BBP, DBP, DINP, DIDP, and DNOP), but not others (e.g., DIBP, DPP, DHP, and DCHP). Among the ten phthalates and seven substitutes for which regulatory standards were not determined, DIBP, DHP, DEHA, DIBA, DINA, and DEHT were detected in children's products made from PVC plastic. DIBP and DHP, which have a reproductive toxicity classification of 1B, were frequently detected in PVC toys. The reproductive toxicity, estrogenicity, and anti-androgenic activity of the unregulated phthalates and their alternatives have been reported in diverse in vitro and in vivo assays. Conclusion: The use of unregulated phthalates and their substitutes in children's products is increasing. Further monitoring and toxicological information on phthalate alternatives is required to develop proper management plans.

• Journal of Pharmacopuncture
• /
• v.19 no.2
• /
• pp.114-121
• /
• 2016

Objectives: Lung cancer remains a deadly disease with unsatisfactory overall survival. Cisplatin, a standard platinum (Pt)-based chemotherapeutic agent, has the potential to inhibit the growth of lung cancer. Its use, however, is occasionally limited by severe organ toxicity. However, until now, no systematic study has been conducted to verify its efficacy with proper experimental support in vivo. Therefore, we examined whether biosynthesized Pt nanoparticles (NPs) inhibited human lung cancer in vitro and in vivo to validate their use in alternative and complementary medicine. Methods: We evaluated the in vitro and the in vivo anticancer efficiencies of biosynthesized Pt NPs in a subcutaneous xenograft model with A549 cells. Severe combined immune deficient mice (SCID) were divided into four groups: group 1 being the vehicle control group and groups 2, 3 and 4 being the experimental groups. Once the tumor volume had reached $70-75mm^3$, the progression profile of the tumor growth kinetics and the body weights of the mice were measured every week for 6 weeks after oral administration of Pt NPs. Doses of Pt NPs of 500, 1,000 and 2,000 mg/kg of body weight were administered to the experimental groups and a dose of honey was administered to the vehicle control group. The efficacy was quantified by using the delay in tumor growth following the administration of Pt NPs of A549 human-lung-cancer xenografts growing in SCID mice. Results: The in vitro cytotoxicity evaluation indicated that Pt NPs, in a dose-dependent manner, inhibited the growth of A549 cells, and the in vivo evaluation showed that Pt NPs at the mid and high doses effectively inhibited and delayed the growth of lung cancer in SCID mice. Conclusion: These findings confirm the antitumor properties of biosynthesized Pt NPs and suggest that they may be a cost-effective alternative for the treatment of patients with lung cancer.

• The Journal of Korean Medicine
• /
• v.32 no.1
• /
• pp.67-83
• /
• 2011

Objectives: The purpose of this study was to examine the single dose toxicity with oral administration and genotoxicities of Ssanghwa-tang fermented with Lactobacillus acidophyllus. Materials and Methods: Clinical signs, weight changes, lethal doses$(LD_{50})$, and postmortem evaluation were determined by Globally Harmonized Classification System(GHCS) in a single-dose oral toxicity study. In vitro mammalian chromosomal aberration test was conducted with Ames test by cell proliferation suppression assessment using the cultivated CHO-K1(Chinese hamster ovary fibroblast) origins. Bacterial reversion assay was performed using Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA). In vivo micronucleus test was performed using ICR mouse bone marrow. Results: No clinical sign was observed and none of the groups with doses up to 2000 mg/kg showed significant acute oral toxicity in the single dose oral administration. None of the sample doses taken during the 6 to 18 hour groups showed significant aberrant metaphases comparing to the negative control group in the in vitro mammalian chromosomal aberration test. No evidence of mutagenicity was seen for Escherichia coli (WP2uvrA) or Salmonella typhimurium (TA98, TA100, TA1535, and TA1537). No significant increase in the frequency of micronuclei was seen in the micronucleus test. Conclusion: These results indicate that the $LD_{50}$ value of Ssanghwa-Tang fermented with Lactobacillus acidophyllus may be over 2000 mg/kg and it have no acute oral toxicity and genotoxicity.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4597-4606
• /
• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• YAKHAK HOEJI
• /
• v.52 no.3
• /
• pp.212-218
• /
• 2008

Manganese is a naturally occurring element which is widespread in the environment. Also, manganese is an essential trace element and plays a key role in important biological reactions catalyzed by enzymes. However, exposure to high levels of manganese can cause toxicity in neurone and inhalation system, also damage in various tissues. We investigated the toxicity induced by manganese compound ($MnCl_2$) in cultured rat cardiomyocytes. Treatment of manganese to cultured cardiomyocyte led to cell death, reactive oxygen species (ROS) increase, and cytosolic caspase-3 activation. The ROS increase was related with the decreased level of glutathione. Expressions of ROS related genes such as heme oxygenase-1, thioredoxin reductase, and NADH quinone oxidase were significantly induced in manganese treated cells. These results suggest that manganese induce oxidative stress and apoptosis in cardiomyocytes, and may be the one of risk factors to cause heart dysfunction in vivo.

• Environmental Mutagens and Carcinogens
• /
• v.18 no.2
• /
• pp.89-92
• /
• 1998

The results of chromosome aberration test in mammalian cells in culture (Chinese hamster lung fibroblast cells) showed no induction of structural and numerical aberrations by YH1226, a cephalosporin antibiotic regardless of metabolic activation, while positive control group (mitomycin C and benzo(a)pyrene) showed structural chromosome aberrations of 25% and 10%, respectively. The in vivo induction of micronuclei was measured in polychromatic erythrocytes in bone marrow of male ddY mouse given YH1226 at 500, 250, 125 mg/kg by i.p. once. After 24 hours, animals were sacrificed and evaluated for the incidence of micronucleated polychromatic erythrocytes in whole erythrocytes. Although a positive response for induction of micronuclei in animals treated with mitomycin C demonstrated the sensitivity of the test system for detection of a chemical clastogen, YH1226 did not induce microunclei in bone marrow of ddY male mice.

• Toxicological Research
• /
• v.30 no.4
• /
• pp.221-234
• /
• 2014

Mitochondria dysfunction was first described in the 1960s. However, the extent and mechanisms of mitochondria dysfunction's role in cellular physiology and pathology has only recently begun to be appreciated. To adequately evaluate mitochondria-mediated toxicity, it is not only necessary to understand mitochondria biology, but discerning mitochondrial redox biology is also essential. The latter is intricately tied to mitochondrial bioenergetics. Mitochondrial free radicals, antioxidants, and antioxidant enzymes are players in mitochondrial redox biology. This review will provide an across-the-board, albeit not in-depth, overview of mitochondria biology and mitochondrial redox biology. With accumulating knowledge on mitochondria biology and mitochondrial redox biology, we may devise experimental methods with adequate sensitivity and specificity to evaluate mitochondrial toxicity, especially in vivo in living organisms, in the near future.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.7
• /
• pp.1015-1022
• /
• 2013

We recently showed that polylysine, the polymer of lysines, retains anti-prion activity. Although the effectiveness of prion inhibition by polylysine was demonstrated with the regimen tolerated in mice, a determination of quantitative polylysine toxicity is necessary to precisely address the in vivo toxicity level of polylysine. In this communication, we report the results of body weight monitoring and hematologic tests performed in CD-1 mice that received two different tolerable dosages of polylysine for an either 5-day or 4-week period. We found that there was no significant alteration in overall serum chemistry, blood cell count, and body weight gain compared with controls. The only notable quantitative change with statistical significance was the decrease of platelet numbers in mice subchronically administered with polylysine. Our results suggest that polylysine is harmless in mice if administered for a short period, but administrations of polylysine in mice may require considerate attention for safety in future investigations as mice chronically receive tolerable doses of polylysine.