• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5963-5966
• /
• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of a combination of gemcitabine and nedaplatin in treating patients with non-small cell lung cancer. Methods: Clinical studies evaluating the efficacy and safety of a combination of gemcitabine and nedaplatin with attention to response and safety for patients with non-small cell lung cancer were identified using a predefined search strategy. Pooled response rates for gemcitabine and nedaplatin were calculated. Results: In gemcitabine and nedaplatin based regimens, 4 clinical studies including 112 patients with non-small cell lung cancer were considered eligible for inclusion. The pooled analysis suggested that the pooled reponse rate was 40.2% (45/112). Main side effects included grade 3-4 neutropenia, thrombocytopenia, and anemia. Grade 3-4 nonhematological toxicity included nausea and vomiting, diarrhea, and hepatic dysfunction. There were no treatment-related deaths. Conclusion: This evidence based analysis suggests that the combination of gemcitabine and nedaplatin is associated with good response rate and accepted toxicity for treating patients with non-small cell lung cancer.

• Molecules and Cells
• /
• v.42 no.6
• /
• pp.480-494
• /
• 2019

Aggregates of disease-causing proteins dysregulate cellular functions, thereby causing neuronal cell loss in diverse neurodegenerative diseases. Although many in vitro or in vivo studies of protein aggregate inhibitors have been performed, a therapeutic strategy to control aggregate toxicity has not been earnestly pursued, partly due to the limitations of available aggregate models. In this study, we established a tetracycline (Tet)-inducible nuclear aggregate (${\beta}23$) expression model to screen potential lead compounds inhibiting ${\beta}23$-induced toxicity. High-throughput screening identified several natural compounds as nuclear ${\beta}23$ inhibitors, including peucedanocoumarin III (PCIII). Interestingly, PCIII accelerates disaggregation and proteasomal clearance of both nuclear and cytosolic ${\beta}23$ aggregates and protects SH-SY5Y cells from toxicity induced by ${\beta}23$ expression. Of translational relevance, PCIII disassembled fibrils and enhanced clearance of cytosolic and nuclear protein aggregates in cellular models of huntingtin and ${\alpha}$-synuclein aggregation. Moreover, cellular toxicity was diminished with PCIII treatment for polyglutamine (PolyQ)-huntingtin expression and ${\alpha}$-synuclein expression in conjunction with 6-hydroxydopamine (6-OHDA) treatment. Importantly, PCIII not only inhibited ${\alpha}$-synuclein aggregation but also disaggregated preformed ${\alpha}$-synuclein fibrils in vitro. Taken together, our results suggest that a Tet-Off ${\beta}23$ cell model could serve as a robust platform for screening effective lead compounds inhibiting nuclear or cytosolic protein aggregates. Brain-permeable PCIII or its derivatives could be beneficial for eliminating established protein aggregates.

• Microbiology and Biotechnology Letters
• /
• v.34 no.4
• /
• pp.357-362
• /
• 2006

A growth inhibition assay using Chlorella sp. AG 10002 based on the OECD 201 standard test procedure was applied to the toxicity testing of endosulfan and its reported metabolites. Comparison of dry cell weight, optical density (OD) at 680 nm, and chlorophyll a concentration indicated that optical density at 680 nm of culture broth is convenient, rapid, and accurate method for cell growth. In this microalgae system, the $IC_{50}$ values of endosulfan, endosulfan sulfate, endosulfan lactone, and endosulfan ether were determined as 9.45, 18.8, 18.2 and 37.5 mg/L, respectively. In a while, endosulfan diol did not show a significant toxicity up to 50 mg/L. Since endosulfan is liable at acidic or alkaline conditions, treatment of endosulfan in pH 3, 4, and 11 for 3 days resulted in reduced toxicity, as expected. These results suggested that the microalgae system is useful to evaluate various toxic chemicals and provide a new notion for bioremediation of endosulfan in aqueous systems.

• Advances in Traditional Medicine
• /
• v.5 no.1
• /
• pp.29-36
• /
• 2005

Polysaccharide hydrogels constitute a structurally diverse class of biological macromolecules with a wide range of physicochemical properties. They also constitute important members of the family of industrial water-soluble polymers. They find application in Pharmacy as binders, disintegrants, suspending, emulsifying and sustaining agents. According to the International Pharmaceutical Excipients Council (IPEC), an excipient must have an established safety profile. Hence, in the present study, in vitro cytotoxicity on Vero and HEp-2 cell lines, and in vivo acute toxicity in rats were carried out to establish the safety of polysaccharide hydrogels from the seeds of Plantago ovata and Ocimum basilicum. The in vitro cytotoxicity was determined by MTT and SRB assays. In the in vivo acute toxicity, the effects of three different doses of hydrogels (100, 200 and 400 mg/kg body weight) on food and water intake, body weight, biochemical and hematological parameters were studied. The results of in vitro did not show any cytotoxicity on both the cell lines used. In the in vivo acute toxicity, the hydrogels did not show any toxic symptoms in all three dose levels. This establishes the safety of the selected hydrogels. Hence, they can be used as excipients in pharmaceutical dosage forms.

• Proceedings of the Korea Society of Environmental Toocicology Conference
• /
• 2003.10a
• /
• pp.13-13
• /
• 2003

Methylmercury (MeHg) is a ubiquitous environmental toxicant that can be exposed to humans by ingestion of contaminated food including fish and bread. MeHg has been suggested to exert its toxicity through its high reactivity to thiols, generation of arachidonic acid and reactive oxygen species (ROS), and elevation of intracellular $Ca^{2+}$ levels (［$Ca^{2+}$］$_{i}$). However, the precise mechanism has not been fully defined. Here we show that phosphatidylcholine-specific phospholipase C (PC-PLC) is a critical pathway for MeHg-induced toxicity. MeHg activated the acidic form of sphingomyelinase (A-SMase) and group IV cytosolic phospholipase $A_2$ ($cPLA_2$) downstream of PC-PLC, but these enzymes as well as protein kinase C were not linked to MeHg's toxicity. Furthermore, MeHg produced ROS, which did not cause the toxicity. However, D6O9, an inhibitor of PC-PLC, significantly reversed the toxicity in a time- and dose-dependent manner in MDCK and SH-5YSY cells. Addition of EGTA to culture media resulted in partial decrease of [$Ca^{2+}$］$_{i}$ and partially blocked cell death. In contrast, D609 completely prevented cell death with parallel decreases in diacylglycerol and ［$Ca^{2+}$］$_{i}$. Together, our findings indicated that MeHg-induced toxicity was caused by elevation of ［$Ca^{2+}$]$_{i}$ through activation of PC-PLC. The toxicity was not attributable to the signaling pathways such as $cPLA_2$, A-SMase, and PKC, or to the generation of ROS.

• Journal of the Korean Society of Tobacco Science
• /
• v.29 no.2
• /
• pp.110-117
• /
• 2007

In vitro toxicity tests such as cytotoxicity, mutagenicity and genotoxicity assay are useful for evaluating the relative toxicity of smoke or smoke condensates obtained from different cigarette configurations. A major disadvantage of these tests is relatively time-consuming, complicated and expensive. Recently, a cell-free glutathione consumption assay (GCA) as a rapid and simple screening method for the toxicity assessment of smoke has been reported by Cahours et al. (CORESTA, 2006). This study was carried out to assess the GCA application capable of predicting the toxicity of gas/vapor phase (GVP) of cigarette smoke and to identify individual compounds responsible for the glutathione (GSH) consumption in smoke. Each GVPs from 2R4F, standard cigarette, carbon filter cigarette (ExC) and new carbon filter cigarette (ExN), test cigarettes were collected by automatic smoking machine and evaluated the relative toxicity by GCA and neutral red uptake (NRU) assay. Toxic compounds existed in smoke were also chosen, relative toxicities of these compounds were screened by using two methods and compared individually. The overall order of toxicity by GCA was 2R4F > ExC > ExN, which was consistent with the result of Neutral Red Uptake assay. The levels of carbonyl compounds of ExN were lower than those of 2R4F and ExC, indicating that GSH consumption was associated with carbonyl compound yields. A major toxicant under current study is acrolein, which contributed to more than half of the GSH consumption. Collectively, the toxicity of GVP determined by GCA method may be mainly attributed to acrolein.

• Korean Journal of Ecology and Environment
• /
• v.50 no.1
• /
• pp.16-28
• /
• 2017

In an aquatic environment, toxicity of metals to organisms depends on external factors (type of metal, exposure concentration and duration, environmental parameters, and water quality) and intracellular processes(metal-binding sites and detoxification). Toxicity of copper(Cu) on the marine microalga Tetraselmis suecica was investigated in this study. Dose-dependent (Cu concentration dependent) inhibition of growth and cell division, as well as, variation of intra- and extra-cellular Cu, Fe and Zn content was observed. T. suecica was sensitive to Cu; the 96 h $EC_{50}$ (concentration to inhibit growth-rate by 50%) of growth rate (${\mu}$) ($21.73{\mu}M\;L^{-1}$), cell division $day^{-1}$ ($18.39{\mu}M\;L^{-1}$), and cells $mL^{-1}$ ($13.25{\mu}M\;L^{-1}$) demonstrate the toxicity of Cu on this microalga. High intra-($19.86Pg\;cell^{-1}$) and extra-cellular($54.73Pg\;cell^{-1}$) Cu concentrations were recorded, on exposure to 24.3 and $72.9{\mu}M\;L^{-1}$ of Cu.

• YAKHAK HOEJI
• /
• v.42 no.4
• /
• pp.388-394
• /
• 1998

The lectin from starfish, Asterina pectinifera, was purified and tested for its potential antitumor activity. It was shown to possess considerable toxicity toward various tumor cell lines. Concentration of Asterina pectinifera lectin (APL) at 4mg/$5{\times}10^5$ cells resulted in 28% death of Ehrlich ascites tumor cell, 40% of L929, 60% of A549, and 52% of HeLa cells after 48 hours incubation. Toxicity of APL to L929, Ehrlich ascites, A549, and HeLa cells revealed a reduction in cell viability of approximately 70% at APL concentration of 8mg/$5{\times}10^5$ cells after 48 hours incubation. Administration of APL ($100{\mu}g/day$ or $300{\mu}g/day$) inhibited the growth of Ehrlich ascites cells in vivo. Mice given only Ehrlich cells survived an average of $15{\pm}1$ (S.E.) days. Mice given Ehrlich cells and $100{\mu}g\;or\;300{\mu}g$ APL had 58% and 67% survival, respectively, after 20 days. These results suggest that APL has antitumor activity.

• Toxicological Research
• /
• v.30 no.3
• /
• pp.193-198
• /
• 2014

Degradation of glucose is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Methylglyoxal is produced during glucose degradation and the levels of methylglyoxal are increased in diabetes patients. In this study we investigated whether methylglyoxal induces mitochondrial impairment and apoptosis in HepG2 cells and induces liver toxicity in vivo. Methylglyoxal caused apoptotic cell death in HepG2 cells. Moreover, methylglyoxal significantly promoted the production of reactive oxygen species (ROS) and depleted glutathione (GSH) content. Pretreatment with antioxidants caused a marked decrease in methylglyoxal-induced apoptosis, indicating that oxidant species are involved in the apoptotic process. Methylglyoxal treatment induced mitochondrial permeability transition, which represents mitochondrial impairment. However, pretreatment with cyclosporin A, an inhibitor of the formation of the permeability transition pore, partially inhibited methylglyoxal-induced cell death. Furthermore, acute treatment of mice with methylglyoxal increased the plasma levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating liver toxicity. Collectively, our results showed that methylglyoxal increases cell death and induces liver toxicity, which results from ROS-mediated mitochondrial dysfunction and oxidative stress.

• The Korean Journal of Physiology and Pharmacology
• /
• v.23 no.2
• /
• pp.121-130
• /
• 2019

Glutamate toxicity-mediated mitochondrial dysfunction and neuronal cell death are involved in the pathogenesis of several neurodegenerative diseases as well as acute brain ischemia/stroke. In this study, we investigated the neuroprotective mechanism of dieckol (DEK), one of the phlorotannins isolated from the marine brown alga Ecklonia cava, against glutamate toxicity. Primary cortical neurons ($100{\mu}M$, 24 h) and HT22 neurons (5 mM, 12 h) were stimulated with glutamate to induce glutamate toxic condition. The results demonstrated that DEK treatment significantly increased cell viability in a dose-dependent manner ($1-50{\mu}M$) and recovered morphological deterioration in glutamate-stimulated neurons. In addition, DEK strongly attenuated intracellular reactive oxygen species (ROS) levels, mitochondrial overload of $Ca^{2+}$ and ROS, mitochondrial membrane potential (${\Delta}{\Psi}_m$) disruption, adenine triphosphate depletion. DEK showed free radical scavenging activity in the cell-free system. Furthermore, DEK enhanced protein expression of heme oxygenase-1 (HO-1), an important anti-oxidant enzyme, via the nuclear translocation of nuclear factor-like 2 (Nrf2). Taken together, we conclude that DEK exerts neuroprotective activities against glutamate toxicity through its direct free radical scavenging property and the Nrf-2/HO-1 pathway activation.