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In vitro cytotoxicity evaluation of biomaterials on human osteoblast cells CRL-1543; hydroxyapatite, natural coral and polyhydroxybutarate

Shamsuria O, Fadilah AS, Asiah AB, Rodiah MR, Suzina AH, Samsudin AR

Med J Malaysia, 2004 May;59 Suppl B:174-5.
PMID: 15468874

The aim of this study was to evaluate the in vitro cytotoxicity of biomaterials; Hydroxyapatite (HA), Natural coral (NC) and Polyhydroxybutarate (PHB). Three different materials used in this study; HA (Ca10(PO4)6(OH)2), NC (CaCO3) and PHB (Polymer) were locally produced by the groups of researcher from Universiti Sains Malaysia. The materials were separately extracted in the complete culture medium (100mg/ml) for 72h and introduced to the osteoblast cells CRL-1543. The viability of osteoblast CRL-1543 cultivated with these extraction materials after 72h incubation period was compared to negative control with neutral red assay by using spectrophotometer at 540nm. The results showed the non-cytotoxicity of the materials. After 72h of incubation period, HA showed 123% viable cells, NC was 99.43% and PHB was 176.75%. In this study, cytotoxicity test dealt mainly with the substances that leached out from the biomaterial. The results obtained showed that the materials were not toxic and also promoted cells growth in the sense of biofunctionality.

Matched MeSH terms: Cell Survival/drug effects*
DNA damage evaluation of hydroxyapatite on fibroblast cell L929 using the single cell gel electrophoresis assay

Rajab NF, Yaakob TA, Ong BY, Hamid M, Ali AM, Annuar BO, et al.

Med J Malaysia, 2004 May;59 Suppl B:170-1.
PMID: 15468872

Hydroxyapatite is the main component of the bone which is a potential biomaterial substance that can be applied in orthopaedics. In this study, the biocompatibility of this biomaterial was assessed using an in vitro technique. The cytotoxicity and genotoxicity effect of HA2 and HA3 against L929 fibroblast cell was evaluated using the MTT Assay and Alkaline Comet Assay respectively. Both HA2 and HA3 compound showed low cytotoxicity effect as determined using MTT Assay. Cells viability following 72 hours incubation at maximum concentration of both HA2 and HA3 (200 mg/ml) were 75.3 +/- 8.8% and 86.7 +/- 13.1% respectively. However, the cytotoxicity effect of ZnSO4.7H2O as a positive control showed an IC50 values of 46 mg/ml (160 microM). On the other hand, both HA2 and HA3 compound showed a slight genotoxicity effect as determined using the Alkaline Comet Assay following incubation at the concentration 200 mg/ml for 72 hours. This assay has been widely used in genetic toxicology to detect DNA strand breaks and alkali-labile site. The percentage of the cells with DNA damage for both substance was 27.7 +/- 1.3% and 15.6 +/- 1.0% for HA2 and HA3 respectively. Incubation of the cells for 24 hours with 38 microg/ml (IC25) of positive control showed an increase in percentage of cells with DNA damage (67.5 +/- 0.7%). In conclusion, our study indicated that both hydroxyapatite compounds showed a good biocompatibility in fibroblast cells.

Matched MeSH terms: Cell Survival/drug effects
Chromosome aberration test for hydroxyapatite in sheep

Kannan TP, Nik Ahmad Shah NL, Azlina A, Samsudin AR, Narazah MY, Salleh M

Med J Malaysia, 2004 May;59 Suppl B:168-9.
PMID: 15468871

The present study is aimed at finding the mutagenicity and cytotoxicity of dense form of synthetic hydroxyapatite (Source: School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia) in the blood of sheep. The biomaterial was implanted in the tibia of Malin, an indigenous sheep breed of Malaysia. Blood was collected from the sheep before implantation of the biomaterial, cultured and a karyological study was made. Six weeks after implantation, blood was collected from the same animal, cultured and screened for chromosome aberrations. The mitotic indices and karyological analysis indicated that the implantation of synthetic hydroxyapatite (dense form) did not produce any cytotoxicity or chromosome aberrations in the blood of sheep.

Matched MeSH terms: Cell Survival/drug effects
In vitro cytotoxicity testing on valued added hydroxyapatite as bone replacement material

Shaari R, Samsudin AR

Med J Malaysia, 2004 May;59 Suppl B:109-10.
PMID: 15468842

The present in vitro evaluation indicated that the value added hydroxyapatite (HA) was more toxic than pure HA but the toxicity of value added HA was slight compared to the positive control. In this testing, the conclusion can be made that value added HA is less biocompatible than commercialized pure HA. This toxicity may be caused by both the particle size and degradation (leaching). Further studies should be carried out to determine whether there is particle size effect or leaching effect when using powder as compared to the block materials. The in vivo evaluation should be done to assess the reaction to this value added HA as compared to the pure HA.

Matched MeSH terms: Cell Survival/drug effects*
Cytotoxicity analysis of poly (carbonate-siloxane-urea) urethane

Kannan RY, Sales KM, Salacinski HJ, Butler PE, Seifalian AM

Med J Malaysia, 2004 May;59 Suppl B:99-100.
PMID: 15468837
Matched MeSH terms: Cell Survival/drug effects*
Challenges associated with the synthesis of unusual o-carboxamido stilbenes by the Heck protocol: Intriguing substituent effects, their toxicological and chemopreventive implications

Kee CH, Ariffin A, Awang K, Takeya K, Morita H, Hussain SI, et al.

Org Biomol Chem, 2010 Dec 21;8(24):5646-60.
PMID: 20941451 DOI: 10.1039/c0ob00296h

The syntheses of fourteen unusual o-carboxamido stilbenes by the Heck protocol revealed surprising complexity related to intriguing substituent effects with mechanistic implications. The unexpected cytotoxic and chemopreventive properties also seem to be substituent dependent. For example, although stilbene 15d (with a 4-methoxy substituent) showed cytotoxicity on HT29 colon cancer cells with an IC(50) of 4.9 μM, the 3,4-dimethoxy derivative (15c) is inactive. It is interesting to observe that the 3,5-dimethoxy derivative (15e) showed remarkable chemopreventive activity in WRL-68 fetal hepatocytes, surpassing the gold standard, resveratrol. The resveratrol concentration needed to be 5 times higher than that of 15e to produce comparable elevation of NQO1.

Matched MeSH terms: Cell Survival/drug effects
Biocompatibility of bio based calcium carbonate nanocrystals aragonite polymorph on NIH 3T3 fibroblast cell line

Kamba AS, Ismail M, Ibrahim TA, Zakaria ZA

Afr J Tradit Complement Altern Med, 2014;11(4):31-8.
PMID: 25392577

BACKGROUND: Currently, there has been extensive research interest for inorganic nanocrystals such as calcium phosphate, iron oxide, silicone, carbon nanotube and layered double hydroxide as a drug delivery system especially in cancer therapy. However, toxicological screening of such particles is paramount importance before use as delivery carrier. In this study we examine the biocompatibility of CaCO3 nanocrystal on NIH 3T3 cell line.
MATERIAL AND METHODS: Transmission and field emission scanning electron microscopy (TEM and FESEM) were used for the characterisation of CaCO3 nanocrystals. Cytotoxicity and genotoxic effect of calcium carbonate nanocrystals in cultured mouse embryonic fibroblast NIH 3T3 cell line using various bioassays including MTT, and Neutral red/Trypan blue double-staining assays. LDH, BrdU and reactive oxygen species were used for toxicity analysis. Cellular morphology was examined by scanning electron microscopy (SEM) and confocal fluorescence microscope.
RESULTS: The outcome of the analyses revealed a clear rod-shaped aragonite polymorph of calcium carbonate nanocrystal. The analysed cytotoxic and genotoxicity of CaCO3 nanocrystal on NIH 3T3 cells using different bioassays revealed no significance differences as compared to control. A slight decrease in cell viability was noticed when the cells were exposed to higher concentrations of 200 to 400 µg/ml, while increase in ROS generation and LDH released at 200 and 400 µg/ml was observed.
CONCLUSIONS: The study has shown that CaCO3 nanocrystal is biocompatible and non toxic to NIH 3T3 fibroblast cells. The analysed results offer a promising potential of CaCO3 nanocrystal for the development of intracellular drugs, genes and other macromolecule delivery systems.

Matched MeSH terms: Cell Survival/drug effects*
Fulltext Protective effect of arachidonic acid and linoleic acid on 1-methyl-4-phenylpyridinium-induced toxicity in PC12 cells

Tang KS

Lipids Health Dis, 2014 Dec 19;13:197.
PMID: 25522984 DOI: 10.1186/1476-511X-13-197

BACKGROUND: Parkinson's disease is a neurodegenerative disorder that is being characterized by the progressive loss of dopaminergic neurons of the nigrostriatal pathway in the brain. The protective effect of omega-6 fatty acids is unclear. There are lots of contradictions in the literature with regard to the cytoprotective role of arachidonic acid. To date, there is no solid evidence that shows the protective role of omega-6 fatty acids in Parkinson's disease. In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity in PC12 cells was examined.
METHODS: Cultured PC12 cells were either treated with MPP+ alone or co-treated with one of the omega-6 fatty acids for 1 day. Cell viability was then assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS: Cells treated with 500 μM MPP+ for a day reduced cell viability to ~70% as compared to control group. Linoleic acid (50 and 100 μM) significantly reduced MPP+-induced cell death back to ~85-90% of the control value. The protective effect could be mimicked by arachidonic acid, but not by ciglitazone.
CONCLUSIONS: Both linoleic acid and arachidonic acid are able to inhibit MPP+-induced toxicity in PC12 cells. The protection is not mediated via peroxisome proliferator-activated receptor gamma (PPAR-γ). Overall, the results suggest the potential role of omega-6 fatty acids in the treatment of Parkinson's disease.

Matched MeSH terms: Cell Survival/drug effects
In vitro degradation and cell viability assessment of Zn-3Mg alloy for biodegradable bone implants

Dambatta MS, Murni NS, Izman S, Kurniawan D, Froemming GR, Hermawan H

Proc Inst Mech Eng H, 2015 May;229(5):335-42.
PMID: 25991712 DOI: 10.1177/0954411915584962

This article reports the in vitro degradation and cytotoxicity assessment of Zn-3Mg alloy developed for biodegradable bone implants. The alloy was prepared using casting, and its microstructure was composed of Mg2Zn11 intermetallic phase distributed within a Zn-rich matrix. The degradation assessment was done using potentiodynamic polarization and electrochemical impedance spectrometry. The cell viability and the function of normal human osteoblast cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alkaline phosphatase extracellular enzyme activity assays. The results showed that the degradation rate of the alloy was slower than those of pure Zn and pure Mg due to the formation of a high polarization resistance oxide film. The alloy was cytocompatible with the normal human osteoblast cells at low concentrations (<0.5 mg/mL), and its alkaline phosphatase activity was superior to pure Mg. This assessment suggests that Zn-3Mg alloy has the potential to be developed as a material for biodegradable bone implants, but the toxicity limit must be carefully observed.

Matched MeSH terms: Cell Survival/drug effects
Comparison of free amino acids, antioxidants, soluble phenolic acids, cytotoxicity and immunomodulation of fermented mung bean and soybean

Ali NM, Yeap SK, Yusof HM, Beh BK, Ho WY, Koh SP, et al.

J Sci Food Agric, 2016 Mar 30;96(5):1648-58.
PMID: 26009985 DOI: 10.1002/jsfa.7267

BACKGROUND: Mung bean and soybean have been individually reported previously to have antioxidant, cytotoxic and immunomodulatory effects, while fermentation is a well-known process to enhance the bioactive compounds that contribute to higher antioxidant, cytotoxic and immunomodulation effects. In this study, the free amino acids profile, soluble phenolic acids content, antioxidants, cytotoxic and immunomodulatory effects of fermented and non-fermented mung bean and soybean were compared.
RESULTS: Fermented mung bean was recorded to have the highest level of free amino acids, soluble phenolic acids (especially protocatechuic acid) and antioxidant activities among all the tested products. Both fermented mung bean and soybean possessed cytotoxicity activities against breast cancer MCF-7 cells by arresting the G0/G1 phase followed by apoptosis. Moreover, fermented mung bean and soybean also induced splenocyte proliferation and enhanced the levels of serum interleukin-2 and interferon-γ.
CONCLUSION: Augmented amounts of free amino acids and phenolic acids content after fermentation enhanced the antioxidants, cytotoxicity and immunomodulation effects of mung bean and soybean. More specifically, fermented mung bean showed the best effects among all the tested products. This study revealed the potential of fermented mung bean and soybean as functional foods for maintenance of good health.

Matched MeSH terms: Cell Survival/drug effects
Silver Nanoparticle Coated Bioactive Glasses--Composites with Dex/CMC Hydrogels: Characterization, Solubility, and In Vitro Biological Studies

Wren AW, Hassanzadeh P, Placek LM, Keenan TJ, Coughlan A, Boutelle LR, et al.

Macromol Biosci, 2015 Aug;15(8):1146-58.
PMID: 25923463 DOI: 10.1002/mabi.201500109

Silver (Ag) coated bioactive glass particles (Ag-BG) were formulated and compared to uncoated controls (BG) in relation to glass characterization, solubility and microbiology. X-ray diffraction (XRD) confirmed a crystalline AgNP surface coating while ion release studies determined low Ag release (<2 mg/L). Cell culture studies presented increased cell viability (127 and 102%) with lower liquid extract (50 and 100 ml/ml) concentrations. Antibacterial testing of Ag-BG in E. coli, S. epidermidis and S. aureus significantly reduced bacterial cell viability by 60-90%. Composites of Ag-BG/CMC-Dex Hydrogels were formulated and characterized. Agar diffusion testing was conducted where Ag-BG/hydrogel composites produced the largest inhibition zones of 7 mm (E. coli), 5 mm (S. aureus) and 4 mm (S. epidermidis).

Matched MeSH terms: Cell Survival/drug effects*
Fulltext Synergistic effect of pH-responsive folate-functionalized poloxamer 407-TPGS-mixed micelles on targeted delivery of anticancer drugs

Butt AM, Mohd Amin MC, Katas H

Int J Nanomedicine, 2015;10:1321-34.
PMID: 25709451 DOI: 10.2147/IJN.S78438

BACKGROUND: Doxorubicin (DOX), an anthracycline anticancer antibiotic, is used for treating various types of cancers. However, its use is associated with toxicity to normal cells and development of resistance due to overexpression of drug efflux pumps. Poloxamer 407 (P407) and vitamin E TPGS (D-α-tocopheryl polyethylene glycol succinate, TPGS) are widely used polymers as drug delivery carriers and excipients for enhancing the drug retention times and stability. TPGS reduces multidrug resistance, induces apoptosis, and shows selective anticancer activity against tumor cells. Keeping in view the problems, we designed a mixed micelle system encapsulating DOX comprising TPGS for its selective anticancer activity and P407 conjugated with folic acid (FA) for folate-mediated receptor targeting to cancer cells.
METHODS: FA-functionalized P407 was prepared by carbodiimide crosslinker chemistry. P407-TPGS/FA-P407-TPGS-mixed micelles were prepared by thin-film hydration method. Cytotoxicity of blank micelles, DOX, and DOX-loaded micelles was determined by alamarBlue(®) assay.
RESULTS: The size of micelles was less than 200 nm with encapsulation efficiency of 85% and 73% for P407-TPGS and FA-P407-TPGS micelles, respectively. Intracellular trafficking study using nile red-loaded micelles indicated improved drug uptake and perinuclear drug localization. The micelles show minimal toxicity to normal human cell line WRL-68, enhanced cellular uptake of DOX, reduced drug efflux, increased DOX-DNA binding in SKOV3 and DOX-resistant SKOV3 human ovarian carcinoma cell lines, and enhanced in vitro cytotoxicity as compared to free DOX.
CONCLUSION: FA-P407-TPGS-DOX micelles show potential as a targeted nano-drug delivery system for DOX due to their multiple synergistic factors of selective anticancer activity, inhibition of multidrug resistance, and folate-mediated selective uptake.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Detoxification of toxic phorbol esters from Malaysian Jatropha curcas Linn. kernel by Trichoderma spp. and endophytic fungi

Najjar A, Abdullah N, Saad WZ, Ahmad S, Oskoueian E, Abas F, et al.

Int J Mol Sci, 2014;15(2):2274-88.
PMID: 24504029 DOI: 10.3390/ijms15022274

The presence of phorbol esters (PEs) with toxic properties limits the use of Jatropha curcas kernel in the animal feed industry. Therefore, suitable methods to detoxify PEs have to be developed to render the material safe as a feed ingredient. In the present study, the biological treatment of the extracted PEs-rich fraction with non-pathogenic fungi (Trichoderma harzianum JQ350879.1, T. harzianum JQ517493.1, Paecilomyces sinensis JQ350881.1, Cladosporium cladosporioides JQ517491.1, Fusarium chlamydosporum JQ350882.1, F. chlamydosporum JQ517492.1 and F. chlamydosporum JQ350880.1) was conducted by fermentation in broth cultures. The PEs were detected by liquid chromatography-diode array detector-electrospray ionization mass spectrometry (LC-DAD-ESIMS) and quantitatively monitored by HPLC using phorbol-12-myristate 13-acetate as the standard. At day 30 of incubation, two T. harzianum spp., P. sinensis and C. cladosporioides significantly (p < 0.05) removed PEs with percentage losses of 96.9%-99.7%, while F. chlamydosporum strains showed percentage losses of 88.9%-92.2%. All fungal strains could utilize the PEs-rich fraction for growth. In the cytotoxicity assay, cell viabilities of Chang liver and NIH 3T3 fibroblast cell lines were less than 1% with the untreated PEs-rich fraction, but 84.3%-96.5% with the fungal treated PEs-rich fraction. There was no inhibition on cell viability for normal fungal growth supernatants. To conclude, Trichoderma spp., Paecilomyces sp. and Cladosporium sp. are potential microbes for the detoxification of PEs.

Matched MeSH terms: Cell Survival/drug effects
Chemical compositions and antioxidative and antidiabetic properties of underutilized vegetable palm hearts from Plectocomiopsis geminiflora and Eugeissona insignis

Ahmad Aufa Z, Hassan FA, Ismail A, Mohd Yusof BN, Hamid M

J Agric Food Chem, 2014 Mar 5;62(9):2077-84.
PMID: 24499380 DOI: 10.1021/jf403481p

Underutilized vegetables are currently studied not only for their nutrient values but also for their health-promoting components for protection against chronic diseases. The present study was performed to evaluate chemical compositions and antioxidant properties of underutilized vegetable palm hearts, namely, lalis (Plectocomiopsis geminiflora) and pantu (Eugeissona insignis). Additionally, the vegetable extracts were evaluated for their activities in the inhibition of digestive enzymes and effects on insulin secretion using BRIN BD11 pancreatic cell lines. Both vegetables contain valuable sources of dietary fiber, potassium, and zinc. For the first time, the phenolic compounds of the vegetables were identified and quantified using HPLC-DAD and LC-ESI-MS. Appreciable amounts of chlorogenic acid were found in the studied vegetables. The sample extracts exhibited potential antioxidant capacities through chemical and biological in vitro assays. High inhibition of α-amylase activity (>50%) was found from the extracts. Thus, it was suggested the vegetable consumption could fulfill the nutrient requirements among local communities.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues

Azmi MN, Din MF, Kee CH, Suhaimi M, Ping AK, Ahmad K, et al.

Int J Mol Sci, 2013;14(12):23369-89.
PMID: 24287912 DOI: 10.3390/ijms141223369

Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50=16.68 µM), colon cancer HT-29 (IC50=7.51 µM) and breast cancer MCF-7 (IC50=21.24 µM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

Matched MeSH terms: Cell Survival/drug effects
Comparative study on human and bovine AT-SC isolation methods

Reshak AH, Shahimin MM, Buang F

Prog Biophys Mol Biol, 2013 Nov;113(2):295-8.
PMID: 24080186 DOI: 10.1016/j.pbiomolbio.2013.09.001

Mammalian adipose tissue derived stem cells (AT-SC) have a tremendous potential in regenerative medicine for tissue engineering and somatic nuclear transfer (SNT). The isolation methods of human and bovine adipose tissue derived stem cells are compared in this paper to determine the feasibility and optimum method of isolation. The optimum isolation method will reduce the processing time, efforts and money as isolation is the first crucial and important step in stem cells research. Human abdominal subcutaneous adipose tissue and bovine abdominal subcutaneous adipose tissue are digested in three collagenase type 1 concentration 0.075%, 0.3% and 0.6% agitated at 1 h and 2 h under 37 °C in 5% CO2 incubator. The cultures are then morphologically characterised. Human adipose tissue stem cells are found to be best isolated using abdominal subcutaneous depot, using 0.075% collagenase type 1 agitated at 1 h under 37 °C in CO2 incubator. While bovine adipose tissue derived stem cells are best isolated using abdominal subcutaneous depot, using 0.6% collagenase type 1 agitated at 2 h under 37 °C in CO2 incubator.

Matched MeSH terms: Cell Survival/physiology
Fulltext Assessment of antioxidant and cytotoxicity activities of saponin and crude extracts of Chlorophytum borivilianum

Ashraf MF, Abd Aziz M, Stanslas J, Ismail I, Abdul Kadir M

ScientificWorldJournal, 2013;2013:216894.
PMID: 24223502 DOI: 10.1155/2013/216894

The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and β -carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL(-1)), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL(-1)). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line.

Matched MeSH terms: Cell Survival/drug effects
Effects of ascorbic acid on PVS2 cryopreservation of Dendrobium Bobby Messina's PLBs supported with SEM analysis

Antony JJ, Keng CL, Mahmood M, Subramaniam S

Appl Biochem Biotechnol, 2013 Sep;171(2):315-29.
PMID: 23832189 DOI: 10.1007/s12010-013-0369-x

Regrowth of the cryopreserved protocorm-like bodies (PLBs) of Dendrobium Bobby Messina was assessed based on the plant vitrification solution 2 (PVS2) optimisation conditions. The optimized protocol obtained based on TTC spectrophotometrical analysis and growth recovery were 3-4 mm of PLBs size precultured in 0.2 M sucrose for 1 day, treated with a mixture of 2 M glycerol and 0.4 M sucrose supplemented with half-strength liquid MS media at 25 °C for 20 min and subsequently dehydrated with PVS2 at 0 °C for 20 min prior to storage in liquid nitrogen. Following rapid warming in a water bath at 40 °C for 90 s, PLBs were treated with unloading solution containing half-strength liquid MS media supplemented with 1.2 M sucrose. Subsequently, the PLBs were cultured on half-strength semi-solid MS media supplemented with 2 % (w/v) sucrose without any growth regulators and resulted in 40 % growth recovery. In addition, ascorbic acid treatment was used to evaluate the regeneration process of cryopreserved PLBs. However, growth recovery rates of non-cryopreserved and cryopreserved PLBs were 30 and 10 % when 0.6 mM ascorbic acid was added. Scanning electron microscopy analysis indicates that there are not much damages observed on both cryopreserved and non-cryopreserved PLBs in comparison to PLBs stock culture.

Matched MeSH terms: Cell Survival/drug effects
Fulltext Sphingosine 1-phosphate receptor 2 (S1P2) attenuates reactive oxygen species formation and inhibits cell death: implications for otoprotective therapy

Herr DR, Reolo MJ, Peh YX, Wang W, Lee CW, Rivera R, et al.

Sci Rep, 2016 Apr 15;6:24541.
PMID: 27080739 DOI: 10.1038/srep24541

Ototoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2(-/-) knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay. This showed that loss of S1P2 results in accumulation of ROS that precedes progressive cochlear degeneration as previously reported. These findings were supported by in vitro cell-based assays to evaluate cell viability, induction of apoptosis, and accumulation of ROS following activation of S1P2 in the presence of cisplatin. We show for the first time, that activation of S1P2 with a selective receptor agonist increases cell viability and reduces cisplatin-mediated cell death by reducing ROS. Cumulatively, these results suggest that S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.

Matched MeSH terms: Cell Survival/drug effects
Predicting points of departure for risk assessment based on in vitro cytotoxicity data and physiologically based kinetic (PBK) modeling: The case of kidney toxicity induced by aristolochic acid I

Abdullah R, Alhusainy W, Woutersen J, Rietjens IM, Punt A

Food Chem Toxicol, 2016 Jun;92:104-16.
PMID: 27016491 DOI: 10.1016/j.fct.2016.03.017

Aristolochic acids are naturally occurring nephrotoxins. This study aims to investigate whether physiologically based kinetic (PBK) model-based reverse dosimetry could convert in vitro concentration-response curves of aristolochic acid I (AAI) to in vivo dose response-curves for nephrotoxicity in rat, mouse and human. To achieve this extrapolation, PBK models were developed for AAI in these different species. Subsequently, concentration-response curves obtained from in vitro cytotoxicity models were translated to in vivo dose-response curves using PBK model-based reverse dosimetry. From the predicted in vivo dose-response curves, points of departure (PODs) for risk assessment could be derived. The PBK models elucidated species differences in the kinetics of AAI with the overall catalytic efficiency for metabolic conversion of AAI to aristolochic acid Ia (AAIa) being 2-fold higher for rat and 64-fold higher for mouse than human. Results show that the predicted PODs generally fall within the range of PODs derived from the available in vivo studies. This study provides proof of principle for a new method to predict a POD for in vivo nephrotoxicity by integrating in vitro toxicity testing with in silico PBK model-based reverse dosimetry.

Matched MeSH terms: Cell Survival/drug effects*

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