Time- and Dose-Dependent Toxicity Studies in 3D Cultures Using a Luminescent Lactate Dehydrogenase Assay

Author(s):  
Natasha Karassina ◽  
Peter Hofsteen ◽  
James J. Cali ◽  
Jolanta Vidugiriene
Author(s):  
Mireille Kameni Poumeni ◽  
Danielle Claude Bilanda ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Yolande Sandrine Mengue Ngadena ◽  
Marguerite Francine Mballa ◽  
...  

AbstractBackgroundLinn (MethodsAqueous extract ofResultsOur findings indicate dose-dependent elevation of nitrites contents in the flowers aqueous extract ofConclusionsdo not possesses neurotoxicity but is able to induce behavioral changes in rats. Therefore, the application of this plant as either drug or supplementary food should be carefully considered.


2002 ◽  
Vol 21 (1) ◽  
pp. 43-48 ◽  
Author(s):  
N Somchit ◽  
S M Hassim ◽  
S H Samsudin

This current study was to investigate the in vitrocytotoxicity of rat hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes contained significantly higher total cytochrome P450 content than the control hepatocytes. P450 content was reduced approximately 30% for both types of hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole was reduced significantly by phenobarbital pretreatment. Phenobarbital did not have any effect on the cytotoxicity induced by fluconazole. These results demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and fluconazole that were expressed in a dose and time-dependent manner. Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.


1973 ◽  
Vol 134 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Philip Davies ◽  
Anthony C. Allison ◽  
A. David Haswell

1. Cytochalasin B (10μg/ml) enhances the release of rabbit polymorphonuclear leucocyte lysosomal acid hydrolases induced by retinol (vitamin A alcohol). 2. This effect is seen at doses of the vitamin that cause selective release of acid hydrolases and those causing more general enzyme release indicated by the loss of lactate dehydrogenase. 3. Cytochalasin B (2–50μg/ml) has no effect on the release of sedimentable acid hydrolases of intact granules obtained from disrupted polymorphonuclear leucocytes. 4. Cytochalasin B (2–10μg/ml) causes a time- and dose-dependent release of mouse peritoneal macrophage acid hydrolases. 5. This effect is selective at all doses of cytochalasin B used, since no release of lactate dehydrogenase, malate dehydrogenase and leucine 2-naphthylamidase was detected. 6. Treatment with cytochalasin B at doses of up to 10μg/ml for as long as 72h did not significantly change the total activities of any of the enzymes measured. 7. The lack of toxicity of cytochalasin B was shown by dye-exclusion tests and its failure to release radioactive colloidal gold stored in secondary lysosomes.


2009 ◽  
Vol 37 (04) ◽  
pp. 759-770 ◽  
Author(s):  
Liang-Liang Peng ◽  
Hong-Mei Shen ◽  
Zheng-Lin Jiang ◽  
Xia Li ◽  
Guo-Hua Wang ◽  
...  

In order to investigate the mechanisms underlying the neuroprotective effect of ginsenoside Rb 3, rat hippocampal neurons were primarily cultured, and exposed to 1 mM N-methyl-D-aspartate (NMDA), cell viability and lactate dehydrogenase leakage were measured. Ca 2+ influx was determined by calcium imaging with a laser confocal microscopy. The influences of ginsenoside Rb 3 on these variables were examined. Patch-clamp technique was used to observe the effects of ginsenoside Rb 3 on NMDA-evoked current. The results show that treatment of Rb 3 raised the neuronal viability, reduced the leakage of lactate dehydrogenase, and inhibited NMDA-elicited Ca 2+ influx in a dose-dependent manner. In the presence of Rb 3, NMDA-evoked peak current was inhibited, and Ca 2+-induced desensitization of NMDA current was facilitated. It is suggested that ginsenoside Rb 3 could exert a neuroprotective role on hippocampal neurons, a role which was partly mediated by the facilitation of Ca 2+-dependent deactivation of NMDA receptors, and the resultant reduction of intracellular free Ca 2+ level.


1999 ◽  
Vol 277 (4) ◽  
pp. L811-L815 ◽  
Author(s):  
Kwang Ho Ko ◽  
Choong Jae Lee ◽  
Chan Young Shin ◽  
Mijeong Jo ◽  
K. Chul Kim

In the present study, we investigated whether polycationic peptides affect mucin release from cultured airway goblet cells. Confluent primary hamster tracheal surface epithelial cells were metabolically radiolabeled with [3H]glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of either poly-l-arginine (PLA) or poly-l-lysine (PLL) to assess the effects on [3H]mucin release. Possible cytotoxicity by the polycations was assessed by measuring lactate dehydrogenase release,51Cr release, and cell exfoliation. The results were as follows: 1) both PLA and PLL inhibited mucin release in a dose-dependent fashion; 2) there was no significant difference in either lactate dehydrogenase release,51Cr release, or the number of floating cells between control and treatment groups; 3) the effects of both PLA and PLL on mucin release were completely blocked by neutralizing the positive charges either by pretreatment with heparin or by N-acetylation of the polycations; and 4) both PLA and PLL completely masked the stimulatory effect of ATP on mucin release. We conclude that these polycationic peptides can inhibit mucin release from airway goblet cells without any apparent cytotoxicity, and the inhibitory effect seems to be attributable to their positive charges. These are the first nonsteroidal agents, to the best of our knowledge, that have been shown to inhibit mucin release from airway goblet cells.


Tumor Biology ◽  
2020 ◽  
Vol 42 (5) ◽  
pp. 101042832091868 ◽  
Author(s):  
Marwa GA Hegazy ◽  
Amal M Imam ◽  
Bassem E Abdelghany

We aimed to assess the antitumor activity of Orobanche crenata methanolic extract and evaluate its cytotoxic effect on different cancer cell lines to develop an effective natural anticancer drug. Components of O. crenata methanolic extract were analyzed using gas chromatography–mass spectrometry. The extract’s antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power procedures and cytotoxicity of the extract was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase assays. Caspase-3 activity was also estimated. O. crenata methanolic extract shows powerful antioxidant activity. The extract inhibited the propagation of human hepatocellular carcinoma (HepG2), human prostate cancer (PC3), human breast adenocarcinoma (MCF-7), and human colon carcinoma (HCT-116) in a dose-dependent manner. O. crenata–treated cells displayed obvious morphological structures distinctive of apoptosis. MTT assay exposed that the extract presented prevention of cell persistence in a dose-dependent means and revealed extremely cytotoxic activity against HepG2, PC3, MCF-7, and HCT-116 with 50% inhibitory concentration values 30.3, 111, 89.6, and 28.6 µg/mL, respectively, after 24 h of incubation. In addition, treatment of HCT-116 with various concentrations of the extract caused the release of lactate dehydrogenase and induction of caspase-3 activity in a dose-dependent way. In conclusion, our findings suggested that the O. crenata extract possesses potent antioxidant, cytotoxic activity, and anticancer properties which are possibly due to the principal bioactive phytochemical composites existing in this plant. These results can be used to develop new drugs for cancer treatment.


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