• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5521-5524
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• 2015

Purpose: This analysis was conducted to evaluate the efficacy and safety of icotinib based regimens in treating patients with non-small cell lung cancer (NSCLC). Methods: Clinical studies evaluating the efficacy and safety of icotinib-based regimens with regard to response and safety for patients with NSCLC were identified using a predefined search strategy. Pooled response rates of treatment were calculated. Results: With icotinib-based regimens, 7 clinical studies which including 5,985 Chinese patients with NSCLC were considered eligible for inclusion. The pooled analysis suggested that, in all patients, the positive reponse rate was 30.1% (1,803/5,985) with icotinib-based regimens. Mild skin itching, rashes and diarrhea were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment-related death occurred in patients treated with icotinib-based regimens. Conclusions: This evidence based analysis suggests that icotinib based regimens are associated with mild response rate and acceptable toxicity for treating Chinese patients with NSCLC.

• 대한한의학방제학회지
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• 제16권2호
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• pp.163-169
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• 2008

The kidney toxicities of BDR-29 used for improvement of the vascular diseases, was examined using male and female Sprague-Dawley rats. The male and female rats were divided into 4 groups for intragastrical treatment with doses of 0, 5, 50, and 500 mg/kg/day for 13 weeks, respectively. In all male and female rats treated with BDR-29, no mortality and gross pathological findings were shown for 13 weeks. There substantially was no change in body weight in all rats with treatment of BDR-29. The renal functional parameters including urinary volume, urine osmolality, electrolytes excretory rate, creatinine clearance, and solute-free water reabsorption were not exchanged in all rats treated with BDR-29. Taken together, these results suggest that BDR-29 has no toxicity on kidney in all male and female rats.

• 한국산업보건학회지
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• 제24권2호
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• pp.169-181
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• 2014

Objectives: The purpose of this study was to obtain information regarding classification and health hazards that may result from a 13-week inhalation exposure to 2-methylpentane by Sprague-Dawley rats. Materials: The testing method was conducted in accordance with OECD guidelines for the testing of chemicals No. 413. The rats were divided into four groups(ten male and ten female rats in each group) and exposed to 0 ppm, 290 ppm, 1,160 ppm, 4,640 ppm 2-Methylpentane in each exposure chamber for six hours per day, five days per week, for 13 weeks. Results: No death or particular clinical presentation including weight change and change of feed rate was observed. The relationships between dose, gender and response were also not significantly changed in urinalysis, hematologic examination, or biochemical examination of blood(except for total cholesterol being up, total protein being up, and chloride ion being down in males), and blood coagulation time. For the relative weight measurement of organs, in the male group the weight change of both kidney and liver were increased in proportion to dose. In histopathological examination, nephropathy in the kidney(cystic change of renal tubules, regenerative tubule, inflammatory cell infiltration and necrosis in the interstitial tissue) was increased in a dose-dependent manner in the male group(290 ppm, 1,160 ppm, 4,640 ppm). However, other organs were not affected by the test substance. Conclusions: 2-methylpentane was estimated as a chemical causing nephropathy in the male group. NOAEL(No Observable Adverse Effect Level) in the female group is more than 4,640 ppm, while inthe male group it is less than 290 ppm.

• Korean Journal of Acupuncture
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• 제22권3호
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• pp.165-174
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• 2005

Objective : The objective of this study is to investigate the inhibitor effects of an traditional oriental herb, Sophora flavescens on the hepatic and renal side effects of chemotherapy by using B16-BL6 melanoma-injected C57BL6 mouse tumor model. Methods : In this study, the effects of an traditional oriental herb, Sophora flavescens, on the side effects of chemotherapy were studied using B16 melanoma-injected C57BL6 mouse tumor model. Results : Sophora flavescen has significant effect on the reduction of the side effects of chemotherapy. Sophora flavescen recovered the reduction of WBC and RBC during cisplatin chemotherapy. Water extract of Sophora flavescens significantly inhibited cisplatin-induced increase of serum blood urea nitrogen (BUN) which is a good indicator of renal toxicity. Sophora flavescens extract does not decrease the anti-tumor activity of cisplatin showing that it can selectively inhibit side effects of anticancer drugs preserving beneficial effort. Conclusion : Theses results suggest a possibility that Sophora flavescens extract can be used for cancer patients for the reduction of the side effects and improving the quality of life during chemotherapy of cancer patients.

• 대한약리학회지
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• 제31권1호
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• pp.103-114
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• 1995

일부 malignant tumor에 Pt-complex의 일상 응용 과정에서 신장독성등의 심한 부작용이 문제점으로 지적되고 있다. 이 연구에서는 기존의 cisplatin보다 항암효과는 우수하면서, 부작용을 감소시킨 새로운 Pt-complex의 개발에 역점을 두었다. 본 연구에서 합성한 Pt(Ⅱ) complex는 carrier ligand로서 1,2-diaminocyclohexane(dach)을 사용하였고, leaving group으로는 diophosphine류인 1,2-bisdiphenylphosphinoethane(DPPE)을 도입하였으며, 물에 대한 용해도를 높이기 위해 dinitrate로 만들었다. 새로이 합성한 [Pt(Ⅱ)(trans-d-dach)(DPPE)]$(NO_3)_2$는 원소 분석, IR 및 $^{13}C-NMR$ 분석 data에 의하여 위의 물질임이 확인되었다. MTT assay method에 의한 항암활성 연구를 통하여 P-388, L-1210 lymphocytic leukemia cell과 SK-OV3 난소암세포에서 항암효과가 인정되었으며, 이 항암효과는 대조 약물로 사용된 cisplatin과 유사하였다. 토끼의 신세뇨관 세포와 인체의 신피질 세포를 이용한 cytotoxity 및 thymidine 섭취율과 인체 신피질 조직 배양을 이용한 glucose consumption 실험을 통하여 모두 cisplatin보다 신장독성이 현저히 감소되었다. 이상의 결과로 보아 Pt(Ⅱ)complexes는 carrier ligand와 leaving group의 선택에 따라 항암활성의 증가와 신독성의 감소를 일으키는 요인으로 보여지며, 이 연구에서 만들어진 Pt(Ⅱ)complex는 앞으로 다각적인 검토를 거쳐 새로운 항암화학요법제로 개발될 가능성이 있을 것으로 생각된다.

• 한국균학회지
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• 제30권2호
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• pp.119-123
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• 2002

저자들은 한국산 야생버섯의 독성을 규명하기 위한 연구의 일환으로 전보에서 68종의 한국산 야생버섯의 용혈활성을 검토하였고 그 중 무우자갈버섯(Hebeloma crustuliniforme)이 열내성 용혈독소를 함유함을 보고하였다. 본 연구에서는 무우자갈버섯의 용혈성분을 냉침한 후, 황산암모늄 침전, 용해도 차이에 따른 분획 및 투석과정을 거쳐 부분정제하였다. 부분정제된 용혈성분은 분자량 분자량 12,000 이상으로서, 용혈 최적온도는 $37^{\circ}C$이고 세척하지 않은 혈액에 대해서 면양 > 랫트 > 사람 ${\geq}$ 마우스 > 닭의 순으로, 세척한 혈액에 대해서는 면양 > 마우스 > 사람 ${\geq}$ 랫트 > 닭의 순으로 용혈활성을 나타내었다. 한편 무우자갈버섯의 냉침액 및 부분정제한 용혈성분을 마우스에 복강투여한 결과, 용혈은 물론 심한 급성 간독성 및 신장독성이 관찰되었다. 이러한 결과들은 독버섯으로 잘 알려진 무우자갈버섯의 독성이 최소한 부분적으로라도 그 용혈성분에 기인할 가능성을 강하게 암시하고 있다.

• Toxicological Research
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• 제34권3호
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• pp.221-229
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• 2018

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman's space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.

• 생명과학회지
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• 제18권1호
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• pp.129-135
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• 2008

Paraquat (PQ)는 전세계적으로 사용되고 있는 제초제의 한 종류이며 독성을 가지고 있다. 가자(terminalia Chebulae)는 오래전부터 설사, 이질, 디프테리아, 기침, 천식 등의 치료제로 중국, 한국 등에서 사용되고 있는 약용식물이다. TCM이 PQ 유도독성에 미치는 영향을 실험한 결과 다음과 같은 결과들을 얻었다. 1. 신장 조직과 폐 조직에서 지질과산화물 함량을 측정해본 결과 PQ 처리군은 정상군에 비해 각각 2배, 2.5배 증가하였으나 TCM 투여군에서는 정상군에 가깝게 감소하였다. 2. 활성산소 생성계 효소에서 cytosolic enzyme system인 aldehyde oxidase, xanthine oxidase 그리고 microsomal enzyme system인 aminopyrine N-demethylase, aniline hydroxylase 활성을 측정한 결과 PQ 처리군에서 활성증가가 나타났으나 TCM 투여군에서는 효소활성이 소량 감소하였다. 3. 활성산소 해독계에 영향을 미치는 superoxide dismutase, catalase, glutathione peroxidase를 측정 한 결과 PQ 처리군은 정상군에 비해 2배 이상의 활성 증가가 나타났고 TCM 투여군의 경우 소량 감소하는 결과가 얻어졌다. 4. 폐 조직의 G-6-phosphatase는 PQ투여군의 경우 활성 저하가 나타났으나 TCM 투여군에서는 효소 활성이 점차 증가하여 300 mg/ml에서는 정상군에 가까운 수치가 나타났다. 5. 폐 조직 중의 collagen 함량은 PQ 투여군의 경우 정상군에 비해 1.5배 증가하였고 가자 메탄올추출물 투여군의 경우 100 mg/kg, 200 mg/kg, 300 mg/kg의 순서로 함량이 점차 감소하는 결과를 얻을 수 있었다. 이상의 결과를 종합하여 볼 때 가자 메탄올추출물은 PQ 유도독성을 신장 및 폐조직에서 효과적으로 경감시키는 것으로 나타났다.

• Toxicological Research
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• 제13권1_2호
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• pp.87-94
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• 1997

This study was carried out to investigate toxicity of insecticide carbofuran and compensatory effects of phenobarbital sodium (PB) in vivo and in vitro. Sprague Dawley male rats were used as experimental animals and divided into carbofuran only administered group and simultaneous application group of carbofuran and PB. At 30 rain and 1, 3, 6, 12, 24, 48 and 96 hrs after each treatment, the animals were sacrificed by decapitation. Kidney were immediately removed, immersed in fixatives, and processed with routine method for light microscopic study. Paraffin sections were stained with H-E, PAM and PAS. $5.0\times 10^4$ cell/ml of NIH 3T3 fibroblast in each well of 24 multidish were cultured: After 24 hours, the cells were treated with solution of six groups; control group cultured in media only, carbofuran $MTT_50$ or $NR_50$ group cultured in the media containing carbofuran $MTT_50$ or $NR_50$ and four experimental groups cultured in the media containing carbofuran $NR_50$ plus various concentratins of PB. After the NIH 3T3 fibroblast of all groups were cultured in same condition for 48 hours, Tetrazolium MTT (MTT) and NR (neutral red) assay were performed to evaluate the cytotoxicity of cell organelles. Under the light microscope, atrophic change of renal corpuscles were frequently observed in 1 and 2 days after carbofuran treatment. The increase of the mesangium was apparent in 1 and 2 days after carbofuran treatment. Necrotic changes of the epithelium and loss of brush border of proximal tubules were most severe at 2 and 3 days after carbofuran treatment, respectively. In contrast, there were no evidences of the toxic effects on renal tissues at 48hrs in carbofuran-PB treated groups. Carbofuran $MTT_50$ and $NR_50$ were 78$\mu M$, 82.5$\mu M$ respectively. MTT and NR quantities were significantly increased in carbofuran-PB 100$\mu M$ treatment group and carbofuran-PB 100$\mu M$ treatment group. On the basis of these results, it is obvious that PB has compensatory effects against carbofuran toxicity.

• Nutrition Research and Practice
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• 제8권1호
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• pp.46-53
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• 2014

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide ($As_2O_3$) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As ($iAs^{III}$) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by $As_2O_3$ exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, $Na^+-K^+$ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of $As_2O_3$ exposure. AST showed a significant protective effect against $As_2O_3$-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to $iAs^{III}$ from natural sources or cancer therapy.