• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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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.

• Herbal Formula Science
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• v.16 no.2
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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.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.24 no.2
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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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• v.22 no.3
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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.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• The Korean Journal of Mycology
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• v.30 no.2
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• pp.119-123
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• 2002

In the previous studies, we surveyed 68 Korean wild mushrooms for their hemolytic activity and found that cold-water extract of Hebeloma crustuliniforme contained heat-resistant hemolysin. In this study, partially purified hemolysin of the mushroom was obtained by cold-water extraction followed by precipitation with ammonium sulfate, solubility fractionation and then dialysis. The hemolysin was found to be > 12,000 in molecular weight and its optimal hemolytic temperature was $37^{\circ}C$ and it's hemolytic activity, on washed erythrocytes and unwashed erythrocytes, respectively, was in the order of sheep > rat > human ${\geq}$ mouse > chicken and sheep > mouse > human ${\geq}$ rat > chicken. When ip injected into ICR mice at 1.38 mg/kg, it incurred prompt hemolysis as well as severe renal toxicity and hepatotoxicity. These results strongly suggest that the toxicity of Hebeloma crustuliniforme, which had been well-known as a toxic wild mushroom, may be at least partly due to its hemolysin.

• Toxicological Research
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• v.34 no.3
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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.

• Journal of Life Science
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• v.18 no.1
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• pp.129-135
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• 2008

Paraquat (1,1-dimethyl 4,4' -dipyridium dichloride; PQ) is a kind of herbicide. Terminalia chebulae (TC) has been used as a medicine in China and in Korea for treating illnesses such as diarrhea, collapsed anus, spasmodic, diphtheria, asthma etc.. This study was to examin new physiological activities of methanol extract of TC (TCM) on the toxicity of PQ. It was observed biochemical effects on the toxicity of PQ in kidney and lung tissues after treatment orally administered 100, 200, 300 mg/kg of TCM daily for two weeks. In the experiment related to the toxicity of PQ, we got following results: renal and pulmonary lipid peroxide contents, activities of aminopyrine N-demethylase, aldehyde oxidase and xanthine oxidase were significantly increased in control group as compared with normal group, in the treatment of TCM the values were decreased as compared with control group. Activities of superoxide dismutase, catalase and glutathione peroxidase which are free radical scavenging enzymes were also increased in control group as compared with normal goup, but were decreased in TCM group as compared with control group. Collagen content and glucose-6-phosphatase activity in lung tissue were increased in control group as compared with normal, but was decreased in TCM group as compared with control group. From these results, we concluded that TCM can playa role as an effective agent to decrease toxicity of PQ.

• Toxicological Research
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• v.13 no.1_2
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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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• v.8 no.1
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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.