• Toxicological Research
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• 제35권2호
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• pp.181-190
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• 2019

Lentinus squarrosulus (Mont.) is an edible wild mushroom with tough fruiting body that belongs to the family Polyporaceae. It is used in ethnomedicine for the treatment of ulcer, anaemia, cough and fever. Recent studies have demonstrated its anticancer, anti-diabetic and antioxidant properties. However, little or no information is available regarding the bioactive components and toxicological study of wild dried L. squarrosulus. Therefore, this study investigated the bioactive components of aqueous extract of boiled wild dried L. squarrosulus and its toxicological effects in rats. The extract of L. squarrosulus was subjected to GC-MS analysis. The acute toxicity test was performed by oral administration of a single dose of up to 5,000 mg/kg extract of L. squarrosulus. In subacute study, the rats were orally administered extract of L. squarrosulus at the doses of 500, 1,000 and 1,500 mg/kg body weight daily for 14 days. The haematological, lipid profile, liver and kidney function parameters were determined and the histopathology of the liver and kidney were examined. The GC-MS analysis revealed the presence of bioactive compounds; 1-tetradecene, fumaric acid, monochloride, 6-ethyloct-3-yl ester, 9-eicosene, phytol, octahydropyrrolo[1,2-a]pyrazine and 3-trifluoroacetoxypentadecane. In acute toxicity study, neither death nor toxicity sign was recorded. In the sub-acute toxicity study, significant differences (p < 0.05) were observed on creatinine, aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglycerides and high-density lipoprotein cholesterol. Whilst no significant differences (p > 0.05) were observed on packed cell volume, heamoglobin, red blood cell, white blood cell and alkaline phosphatase, in all the tested doses. No histopathological alterations were recorded. Our findings revealed that aqueous extract of L. squarrosulus may have antimicrobial, antinocieptive and antioxidant properties based on the result of GC-MS analysis. Results of the toxicity test showed no deleterious effect at the tested doses, suggesting that L. squarrosulus is safe for consumption at the tested doses.

• Toxicological Research
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• 제23권2호
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• pp.159-164
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• 2007

Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.

• Preventive Nutrition and Food Science
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• 제11권2호
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• pp.115-119
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• 2006

The object of this study was to examine whether the germanium fortified yeast administered to SD rat is accumulated in the liver and kidney. The administration doses were within 2,000 mg/kg which is the level of NOAEL (no observed adverse effect level) proved through the previous study of single/consecutive oral toxicity test. There were no significant clinical symptoms and mortality following the administration of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg) during the whole test period, and also no difference in the consumed amount of feed and water for each group. No significant abnormalities of hematology and blood chemistry parameters were found in all groups of organic germanium-fortified yeast (0, 500, 1,000, 2,000 mg/kg). The amount of germanium accumulated in liver and kidney was 0 g/kg by ICP-AES method in the group of organic germanium-fortified yeast. In the positive control group of $GeO_2$ (150 mg/kg), the amount of accumulation was shown to 3135.0 and 4277.2 g/kg in each female and male kidney and 1044.3 and 2135.8 g/kg in each female and male liver, respectively. Organic germanium-fortified yeast, a biosynthetic product resulting from putting germanium into yeast, did not show any clinical symptoms, blood chemical significance, and residues in kidney and liver. It could be inferred that the non-toxic amount of organic germanium-fortified yeast was up to 2,000 mg/kg.

• 한국식품영양과학회지
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• 제34권8호
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• pp.1169-1174
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• 2005

본 연구는 다이옥신(2,3,7,8-tetrachlorodibenzo-P-dioxin, TCDD)에 노출된 랫드에 있어 녹용의 고환 독성에 대한 방어 효과를 조사하기 위하여 수행되었다. 실험은 30마리의 수컷 랫드를 10마리씩 3개군으로 나누어 정상대조군(CO)에는 vehicle을 TCDD-단독투여군(TA)과 녹용 에탄올 추출물(EAV) 투여군(TE)에는 50 $\mu$g/kg body weight의 다이옥신을 일회 복강내 주사하였다. TE는 다이옥신 노출 1주 전부터 녹용 에탄올 추출물을 20 mg/kg body weight씩 5주 동안 매일 복강 주사하였다 TA에서는 다이옥신에 의한 체중감소(CO 대비 61.1$\%$)가 현저하였으며 TE 역시 체중은 감소(CO 대비 77.0$\%$)하였으나 YA와 비교해 볼 때 그 정도는 유의하게 경감되 는 것을 알 수 있었다. 다이옥신(TCDD)에 의하여 야기되는 고환 중량, 정세관의 직경 및 Johnsen's score의 감소와 고환조직의 병변은 녹용 에탄올 추출물 투여에 의하여 유의하게 경감되었다. 이상의 결과로 보아 녹용은 랫드에 있어 다이옥신에 의하여 야기되는 고환 독성을 경감시킬 수 있다고 판단한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5863-5868
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• 2015

Nicotine-derived nitrosamine ketone (NNK) is considered a key tobacco smoke carcinogen inducing lung tumors. Physalis peruviana L (harankash) is considered one plant with marked health benefits. This study aimed to evaluate Physalis peruviana L effect on the toxic effect of NNK induced lung cancer in the rats by using pulmonary histopathological, immunohistochemical and DNA flow cytometric analyses. Sixty adult male rats were divided into four groups, each consisting of fifteen animals. The first group received saline, the second received two successive toxic doses of NNK only while the third received two successive toxic doses of NNK with a single daily dose of Physalis peruviana L. The fourth group received a single daily dose of Physalis peruviana L only. Toxic doses of NNK induced hyperplasia and adenocarcinoma in the lung and positive immunoreactivity for Ki-67 and p53 staining with disturbance of the lung DNA content. Administration of Physalis peruviana L with NNK led to a mild pulmonary hyperplasia and weak expression of Ki-67 and p53 with an improvement in the lung DNA content. Physalis peruviana L may protect against NNK induced lung carcinogenesis due to its antioxidant and anti-proliferative effects.

• Toxicological Research
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• 제33권3호
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• pp.255-263
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• 2017

Chemotherapy is associated with male infertility. Cisplatin (cis-diamminedichloro-platinum (II) (CDDP) as a chemotherapy medication used to treat a number of cancers has been reported to most likely induce testicular toxicity. Administration of antioxidants, such as pentoxifylline (PTX) may reduce some Adverse Drug Reactions (ADRs) of CDDP. Therefore, this study investigated the potentially protective effects of PTX on CDDP-induced testicular toxicity in adult male rats. For this purpose, 42 male rats were randomly divided into 7 groups. The rats were orally pretreated with PTX at the 3 doses of 75, 150, and 300 mg/kg once a day for 14 successive days. On the $14^{th}$ day of the study, they were intraperitoneally (IP) administered with a single dose of CDDP (7 mg/kg). Finally, the sperm/testis parameters, serum levels of reproductive hormones, including testosterone, Luteinizing Hormone (LH), and Follicle Stimulating Hormone (FSH) as the pivotal endocrine factors controlling testicular functions, and histopathological changes of testis tissue were examined. Pretreatment with the two doses of 75 and 150 mg/kg PTX indicated significant increases in the sperm count and motility induced by CDDP administration. The right and significantly left testis weights were decreased following the treatment with 300 mg/kg of PTX plus CDDP. However, 75 mg/kg of PTX plus CDDP showed the best near-to-normal histopathological features. The results demonstrated that PTX alone enhanced some parameters, such as the sperm count, while reducing other parameters, including sperm fast motility and germ layer thickness. Furthermore, despite testosterone or LH levels, the mean serum FSH level was significantly augmented by the doses of 75 and 150 mg/kg. It was concluded that PTX administration cannot reduce CDDP-induced testicular toxicity even at high doses (e.g., 300 mg/kg), while it seemed to partially intensify CDDP toxicity effects at a dose of 75 mg/kg. Thus, further research is required in this regard.

• 한국균학회지
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• 제46권3호
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• pp.295-306
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• 2018

본 연구에서는 국내산 50% 에탄올 복령추출물(KPE)과 중국산 50% 에탄올 복령추출물(CPE)의 약리활성 비교를 위하여 전 지방세포주인 3T3-L1 세포주와 암세포주인 Sarcoma 180 세포주를 이용하여 지방축적 억제활성과 항암활성을 비교하였다. 또한 노지재배 및 시설재배의 1년산 복령과 2년산 복령의 50% 에탄올 복령추출물(LPE, FPE)에 대해서도 50% 항암억제활성($IC_{50}$)로 중국산 복령과 비교하였다. 추가적으로 현재 시중에서 유통되고 CPE와 KPE의 안전성 자료를 획득하고자 단회 경구 독성시험을 실시하였다. CPE와 KPE를 3T3-L1 세포에 처리 후 48시간 이후에 대조군과 비교 시 지방축적 억제를 보였으나(p< 0.05), CPE와 KPE 사이에서는 지방축적 억제활성의 차이가 없었다. Sarcoma 180에 대한 CPE와 KPE의 항암활성을 비교할 때 시험한 농도에서 유사한 활성을 보였지만 $300{\mu}g/mL$의 고농도에서는 KPE가 CPE보다 높은 항암활성을 보였다(p < 0.05). 중국산 복령을 대체하고자 인공재배에서 생산된 노지재배 복령(LPE)과 시설재배 복령(FPE)의 항암활성 비교에서 CPE의 항암활성보다 높게 나타났다(p < 0.05). 단회 독성시험에서 CPE와 KPE의 $LD_{50}$(반수치사량)은 2,000 mg/kg 이상으로 추정되었다. 위의 결과를 종합 시 암세포주인 Sarcoma 180 세포주를 이용한 항암활성측정법은 중국산과 국내산의 원산지 검증의 생물활성검증의 보조수단으로 활용이 가능할 것으로 기대되었다. 국내에서 인공재배 되는 노지재배 복령 및 시설재배 복령은 중국산 복령을 대체하여 수입 감소의 효과를 기대할 수 있으며 지방축적 억제활성 및 항암활성의 기능성 원료로 활용이 가능할 것으로 생각되었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7331-7335
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• 2015

Background: Concurrent chemoradiation with three weekly high dose cisplatin is the non-surgical standard of care for the treatment of locally advanced head and neck cancers. Although this treatment regime is efficacious, it has high acute toxicity, which leads not only to increased treatment cost, but also to increased overall treatment time. Hence, the current study was undertaken to evaluate the acute toxicity and tumor response in head and neck cancer patients treated with concurrent chemoradiation using $40mg/m^2$ weekly cisplatin, which has been our institutional practice. Materials and Methods: This single institution retrospective study included data for 287 head and neck cancer patients treated with concurrent chemoradiation from 2012 to 2014. Results: The mean age of the patients was 48.8 years. The most common site of involvement was oral cavity. Most of the study patients presented with advanced stage disease. The mean overall treatment time was 56.9 days. Some 67.2% had overall complete response to treatment as documented till 90 days from the start of treatment. According to the Radiation Therapy Oncology Group (RTOG) acute radiation morbidity scoring criteria, mucositis was seen in 95.1% of the patients. Dermatitis and emesis were observed in 81.9% and 98.6%, respectively. Regarding haematological toxicity, 48.8% and 29.6% suffered from anaemia and leukopenia, respectively, during treatment. Acute kidney injury was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), and was found in 18.8% of the patients. Conclusions: Concurrent chemoradiotherapy with weekly cisplatin is an effective treatment regime for head and neck cancers with reasonable toxicity which can be used in developing countries, where cost of treatment is so important.

• 생명과학회지
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• 제19권8호
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• pp.1152-1158
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• 2009

본 연구는 우리나라에 분포하는 광대버섯인 amanita muscaria로 단회투여독성시험과 반복투여독성시험을 하였을 때 SD 랫드의 독성병리학적 변화를 알아보고자 수행하였다. 단회투여독성시험은 강경증, 경사판법, 정압자극법을 이용하여 측정하였다. 강경증은 33 mg/kg의 농도에서 투여 2${\sim}$3 시간 후 강경증 시간이 감소하였다. 경사판법의 경우 33 mg/kg의 농도에서 투여 2시간 후 대조군과 비교하였을 때 낮은 경사 각도에서도 쉽게 미끄러졌으며, 앞다리 보다는 뒷다리 쪽에서의 움직임 감소를 보였다. 정압자극법의 경우 대조군, 저용량군, 중간용량군에서 SD 랫드가 자극을 인지하는 시간이 1${\sim}$2초 정도로 짧고 매우 공격적인 반응을 보였지만, 고용량군에서는 자극인지 시간이 대략 3${\sim}$5초로 증가하였으며, 대부분 공격적인 반응을 보이지 않는 것이 관찰되었다. 강경증, 경사판법, 정압자극법 모두 투여 4시간 후 대조군과 비슷한 수치로 회복되었으며 이것으로 보아 섭취 4시간 전후에는 amanita muscaria의 독성이 현저히 감소하는 것으로 확인되었다. 반복투여독성시험은 혈액, 혈청분석, 조직 병리학적 검사를 실시하였다. 혈청 분석에서 투여군과 대조군을 비교하였을 때 BUN과 creatinine의 변화는 없었지만 ALT와 LDH는 투여군에서 증가하였다. 이러한 결과를 바탕으로 표적장기인 간과 신장의 손상을 의심하였고 조직 병리학적 검사를 통해 간과 신장의 손상을 확인할 수 있었다.

• 한국식품저장유통학회지
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• 제19권2호
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• pp.315-321
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• 2012

본 연구는 김치에서 분리한 항진균 및 항세균 활성을 나타내는 $Lb.$ $plantarum$ AF1을 분리하여 이 균의 천연 식품보존제 및 사료보존제로서 사용 적합성 및 안전성을 평가하고자 단회 급성독성시험을 실시하였다. 급성독성시험을 위하여 경구 혹은 복강으로 1회 시험물질을 최고 용량(경구: 5,000 mg/kg, 복강: 2,500 mg/kg)으로 하여 ICR계통 암 수 마우스에게 용량별 각 군당 10마리씩 투여한 후 14일간의 일반증상, 사망률, 체중, 임상증상 및 육안적 소견을 관찰하였다. 단회 경구투여 혹은 복강주사한 후 모든 시험군에서 사망례가 관찰되지 않았으며, 시험동물은 시험 종료 시까지 계속 생존하여 평균치사량을 산출할 수 없었다. 복강 혹은 경구투여한 후 마우스의 체중변화에 있어서도 암 수 모두 대조군과 시료물질 투여군 사이에 유의성 있는 차이는 보이지 않았으며, 용량 의존적인 차이도 볼 수 없었다. 경구구투여 혹은 복강주사 단회 투여한 후 시험 종료한 다음 생존동물 모두를 부검하여 주요 장기의 육안적 소견을 관찰한 결과 대조군과 시료투여군 모두에서 외관상이나 내부장기에 어떠한 이상소견이나 병변이 관찰되지 않았다. 이상의 결과로부터 시험물질인 $Lb.$ $plantarum$ AF1는 경구투여 혹은 복강주사 시 ICR계통 암 수 마우스에서 독성학적인 변화가 관찰되지 않았으며, $LD_{50}$은 복강주사가 2,500 mg/kg, 경구투여가 5,000 mg/kg 이상인 저독성의 안전한 물질로 사료된다.