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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*
Size-related assessment on viability and insulin secretion of caprine islets in vitro

Vakhshiteh F, Allaudin ZN, Mohd Lila MA, Hani H

Xenotransplantation, 2013 02 14;20(2):82-8.
PMID: 23406308 DOI: 10.1111/xen.12023

BACKGROUND: The successful isolation, purification, and culture of caprine islets has recently been reported. The present study shows arange of size distribution in caprine islet diameter from 50 to 250 μm, in which 80% of the total islet yield was comprised of small islets.
METHODS: Caprine islets were isolated and purified. Islets were handpicked and the diameter of the islets was recorded using light microscopy. Viablility of the islets was analyzed by confocal microscopy. Insulin secretion assay was carried out and analyzed by ELISA.
RESULTS: When tested at 48 h after isolation, these small islets were 29.3% more viable compared to the large-sized islets. Large islets showed a high ratio (P

Matched MeSH terms: Cell Survival/physiology
Cryopreservation of whole seeds and excised embryonic axes of Citrus suhuiensis cv. limau langkat in accordance to their desiccation sensitivity

Makeen MA, Noor NM, Dussert S, Clyde MM

Cryo Letters, 2005 Jul-Aug;26(4):259-68.
PMID: 19827255

Following the investigation of desiccation sensitivity and freezing tolerance of the whole seed of Citrus suhuiensis cv. limau langkat, desiccation sensitivity and cryopreservation of the excised embryonic axes from the seeds of the same species were examined. Three drying conditions were employed: desiccation by equilibrium for the whole seeds and desiccation in laminar airflow and over silica gel for the excised embryonic axes. The relevance of desiccation sensitivity (WC50) to cryopreservation of whole seeds and excised axes was investigated. High desiccation tolerance (WC50 = 0.034 g H2O x g(-1)dw) was acquired for axes desiccated with faster dehydration rate (1.5 g x g(-1) x h(-1)) in laminar airflow compared to substantially lower desiccation tolerance (WC50 = 0.132 and 0.110 g H2O x g(-1)dw) acquired under slower dehydration rates (1.0 and 0.005 g x g(-1) x h(-1)) for axes desiccated over silica gel and whole seeds desiccated by equilibrium respectively. While few whole seeds (8.3%) survived freezing, high recovery percentages of axes (83.3% and 62.2%) after freezing were obtained under laminar airflow and silica gel drying conditions respectively. Irrespective of the drying method employed, axes survival percentages after exposure to LN temperature commensurate with the desiccation sensitivity pattern. For the whole seeds, a factor other than desiccation sensitivity that limits the tolerance to exposure to LN temperature seems to exist and still needs to be defined.

Matched MeSH terms: Cell Survival/physiology
Fulltext Brazilian red propolis: phytochemical screening, antioxidant activity and effect against cancer cells

de Mendonça IC, Porto IC, do Nascimento TG, de Souza NS, Oliveira JM, Arruda RE, et al.

BMC Complement Altern Med, 2015 Oct 14;15:357.
PMID: 26467757 DOI: 10.1186/s12906-015-0888-9

BACKGROUND: The implementation of new public healthcare models that stimulate the use of natural products from traditional medicine, as a so-called integrated medicine, refers to an approach that use best of both conventional medicine and traditional medicine. Propolis is a widely used natural product by different ancient cultures and known to exhibit biological activities beneficial for health. The large number of studies conducted with propolis had shown that its chemical composition differs as a function of the climate, plant diversity and bee species and plays an important role on its therapeutic properties. The aim of this study was to analyse the phytochemical profile of the ethanolic extract of red propolis (EEP) and its fractionation, antioxidant action of EEP and its fractions hexane, cloroform and ethyl acetate and cytotoxic activity of EEP on human tumour cell lines SF-295 (glioblastoma), OVCAR-8 (ovary) and HCT-116 (colon).
METHODS: EEP was obtained by maceration with absolute ethanol, then it was concentrated in rotaevaporator up to complete evaporation of the solvent. The crude extract was fractionated with hexane, ethyl acetate, chloroform and methanol and they were subjected to phytochemical screening and total phenolic compounds. Antioxidant activity of EEP and fractions was done by means of the 2,2-diphenyl-1-picryhydrazyl (DPPH) method. Biomarkers of red propolis were identified by LC-Orbitrap-FTMS. To assess cytotoxic activity of the extract, cells were exposed to EEP over 72 h. Cell viability was assessed by means of MTT assay. The percentage of cell growth inhibition (IC50) was analysed by means of non-linear regression, and the absorbance values of the various investigated concentrations were subjected to one-factor analysis of variance (ANOVA) followed by Tukey's or Tamhane's tests (α = 0.05).
RESULTS: The results obtained using phytochemical screening and LC-Orbitrap-FTMS indicated the presence of phlobaphene tannins, catechins, chalcones, aurones, flavonones, flavonols, xanthones, pentacyclic triterpenoids and guttiferones in Brazilian red propolis. EEP and its hexane, chloroform and ethyl acetate fractions obtained by liquid-liquid partitioning exhibited satisfactory antioxidant percentages. EEP (IC50 cell lines tested when compared to negative control.
CONCLUSIONS: C-Orbitrap-FTMS was useful to establish the chemical profile of the red propolis. Brazilian red propolis has antioxidant properties and decreases substantially the percentage of cell survival of human tumour cells; thus, it has potential to serve as an anticancer drug.

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
Efficacy of cocoa pod extract as antiwrinkle gel on human skin surface

Abdul Karim A, Azlan A, Ismail A, Hashim P, Abd Gani SS, Zainudin BH, et al.

J Cosmet Dermatol, 2016 Sep;15(3):283-95.
PMID: 27041391 DOI: 10.1111/jocd.12218

OBJECTIVE: Cocoa pods are abundant waste materials of cocoa plantation, which are usually discarded onto plantation floors. However, due to poor plantation management, the discarded cocoa pods can create suitable breeding ground for Phytophthora palmivora, which is regarded as the causal agent of the black pod disease. On the other hand, cocoa pods potentially contain antioxidant compounds. Antioxidant compounds are related to the protection of skin from wrinkles and can be used as functional cosmetic ingredients. Therefore, in this study, cocoa pods were extracted and to be used as active ingredients for antiwrinkles.
METHODS: The active compounds in cocoa pod extracts (CPE) were screened using liquid chromatography-mass spectrometry (LC-MS). Fibroblast cells were used to determine the effective concentration of CPE to maintain the viability for at least 50% of the cells (EC50 ). The gel was tested by 12 panelists to determine the efficacy of CPE in gel form using Visioscan to reduce skin wrinkles and improve skin condition.
RESULTS: CPE was detected to contain malic acid, procyanidin B1, rosmarinic acid, procyanidin C1, apigenin, and ellagic acid, all of which may contribute to functional cosmetic properties of CPE. The EC50 value of cocoa pod extracts was used to calculate the amount of CPE to be incorporated into gel so that the formulated product could reach an effective concentration of extract while being nonintoxicant to the skin cell. The results showed that CPE is potential ingredient to reduce wrinkles. Skin wrinkles reduced at 6.38 ± 1.23% with the application of the CPE gel within 3 weeks and significantly improved further (12.39 ± 1.59%) after 5 weeks. The skin hydration increased (3.181 ± 1.06%) after 3 weeks of the CPE gel application.
CONCLUSION: Flavonoid compounds in CPE contributed to the functional cosmetic properties of CPE. The CPE which is nontoxic to skin cells help to reduce wrinkles on skin after 3 weeks of application. CPE can be used as the active ingredients in antiwrinkle products, and prolonged application may result in significant visual changes to the naked eyes.

Matched MeSH terms: Cell Survival/drug effects
An evaluation of novel real-time technology as a tool for measurement of radiobiological and radiation-induced bystander effects

Ibahim MJ, Crosbie JC, Paiva P, Yang Y, Zaitseva M, Rogers PA

Radiat Environ Biophys, 2016 May;55(2):185-94.
PMID: 26994995 DOI: 10.1007/s00411-016-0641-x

The xCELLigence real-time cell impedance system uses a non-invasive and label-free method to create a cell index that is a composite measure of cell proliferation. The aim of this study was to evaluate xCELLigence against clonogenic assay (gold standard) for measuring radiobiological effects and radiation-induced bystander effects (RIBE). A radiobiological study was conducted by irradiating EMT6.5, 4T1.2 and NMUMG cell lines with different radiation doses, while a RIBE study was done using transfer of conditioned media (CM) harvested from donor to the same type of recipient cell (EMT6.5, 4T1.2, NMUMG, HACAT and SW48). CM was harvested using two protocols which differed in the dose chosen and the exposure to the recipient cells. Results showed that xCELLigence measured a radiobiological effect which correlated with the clonogenic assay. For the RIBE study, no statistically significant differences were observed between xCELLigence or clonogenic survival in control or recipient cells incubated with CM in protocol one. However, there was a significant increase in cell index slope using CM from EMT-6.5 cells irradiated at 7.5 Gy compared with the control group under the second protocol. No other evidence of RIBE was detected by either xCELLigence or clonogenic assay. In conclusion, xCELLigence methods can measure radiobiological effects and the results correlate with clonogenic assay. We observed a lack of RIBE in all tested cell lines with the clonogenic assay; however, we observed a RIBE effect in EMT6.5 cells under one particular protocol that showed RIBE is cell type dependent, is not universally observed and can be detected in different assays.

Matched MeSH terms: Cell Survival/radiation 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
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
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 Ampelopsin E Reduces the Invasiveness of the Triple Negative Breast Cancer Cell Line, MDA-MB-231

Tieng FYF, Latifah SY, Md Hashim NF, Khaza'ai H, Ahmat N, Gopalsamy B, et al.

Molecules, 2019 Jul 18;24(14).
PMID: 31323836 DOI: 10.3390/molecules24142619

Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.

Matched MeSH terms: Cell Survival/drug effects
An Evaluation of Curcumin-Encapsulated Chitosan Nanoparticles for Transdermal Delivery

Nair RS, Morris A, Billa N, Leong CO

AAPS PharmSciTech, 2019 Jan 10;20(2):69.
PMID: 30631984 DOI: 10.1208/s12249-018-1279-6

Curcumin-loaded chitosan nanoparticles were synthesised and evaluated in vitro for enhanced transdermal delivery. Zetasizer® characterisation of three different formulations of curcumin nanoparticles (Cu-NPs) showed the size ranged from 167.3 ± 3.8 nm to 251.5 ± 5.8 nm, the polydispersity index (PDI) values were between 0.26 and 0.46 and the zeta potential values were positive (+ 18.1 to + 20.2 mV). Scanning electron microscopy (SEM) images supported this size data and confirmed the spherical shape of the nanoparticles. All the formulations showed excellent entrapment efficiency above 80%. FTIR results demonstrate the interaction between chitosan and sodium tripolyphosphate (TPP) and confirm the presence of curcumin in the nanoparticle. Differential scanning calorimetry (DSC) studies of Cu-NPs indicate the presence of curcumin in a disordered crystalline or amorphous state, suggesting the interaction between the drug and the polymer. Drug release studies showed an improved drug release at pH 5.0 than in pH 7.4 and followed a zero order kinetics. The in vitro permeation studies through Strat-M® membrane demonstrated an enhanced permeation of Cu-NPs compared to aqueous curcumin solution (p ˂ 0.05) having a flux of 0.54 ± 0.03 μg cm-2 h-1 and 0.44 ± 0.03 μg cm-2 h-1 corresponding to formulations 5:1 and 3:1, respectively. The cytotoxicity assay on human keratinocyte (HaCat) cells showed enhanced percentage cell viability of Cu-NPs compared to curcumin solution. Cu-NPs developed in this study exhibit superior drug release and enhanced transdermal permeation of curcumin and superior percentage cell viability. Further ex vivo and in vivo evaluations will be conducted to support these findings.

Matched MeSH terms: Cell Survival/drug effects
Comparative analysis of antioxidant and antiproliferative activities of Rhodomyrtus tomentosa extracts prepared with various solvents

Abd Hamid H, Mutazah R, Yusoff MM, Abd Karim NA, Abdull Razis AF

Food Chem Toxicol, 2017 Oct;108(Pt B):451-457.
PMID: 27725206 DOI: 10.1016/j.fct.2016.10.004

Rhodomyrtus tomentosa (Aiton) Hassk. has a wide spectrum of pharmacological effects and has been used to treat wounds, colic diarrhoea, heartburns, abscesses and gynaecopathy. The potential antiproliferative activities of R. tomentosa extracts from different solvents were evaluated in vitro on HepG2, MCF-7 and HT 29 cell lines while antioxidant activity was monitored by radical scavenging assay (DPPH), copper reducing antioxidant capacity (CUPRAC) and β-carotene bleaching assay. Extracts from R. tomentosa show the viability of the cells in concentration-dependent manner. According to the IC50 obtained, the ethyl acetate extracts showed significant antiproliferative activity on HepG2 (IC50 11.47 ± 0.280 μg/mL), MCF-7 (IC50 2.68 ± 0.529 μg/mL) and HT 29 (IC50 16.18 ± 0.538 μg/mL) after 72 h of treatment. Bioassay guided fractionation of the ethyl acetate extract led to the isolation of lupeol. Methanol extracts show significant antioxidant activities in DPPH (EC50 110.25 ± 0.005 μg/ml), CUPRAC (EC50 53.84 ± 0.004) and β-carotene bleaching (EC50 58.62 ± 0.001) due to the presence of high total flavonoid and total phenolic content which were 110.822 ± 0.017 mg butylated hydroxytoluene (BHT)/g and 190.467 ± 0.009 mg gallic acid (GAE)/g respectively. Taken together, the results extracts show the R. tomentosa as a potential source of antioxidant and antiproliferative efficacy.

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*
Influence of freeze-drying and spray-drying preservation methods on survivability rate of different types of protectants encapsulated Lactobacillus acidophilus FTDC 3081

Tang HW, Abbasiliasi S, Murugan P, Tam YJ, Ng HS, Tan JS

Biosci Biotechnol Biochem, 2020 Sep;84(9):1913-1920.
PMID: 32448058 DOI: 10.1080/09168451.2020.1770572

The aims of this study were to compare the effectiveness of different drying methods and to investigate the effects of adding a series of individual protectant such as skim milk, sucrose, maltodextrin, and corn starch for preserving Lactobacillus acidophilus FTDC 3081 cells during spray and freeze-drying and storage at different temperatures. Results showed a remarkable high survival rate of 70-80% immediately after spray- and freeze-drying in which the cell viability retained at the range of 109 to 1010 CFU/mL. After a month of storage, maltodextrin showed higher protective ability on both spray- and freeze-dried cells as compared to other protective agents at 4°C, 25°C, and 40°C. A complete loss in viability of spray-dried L. acidophilus FTDC 3081 was observed after a month at 40°C in the absence of protective agent.

Matched MeSH terms: Cell Survival/drug effects
Preparation of letrozole dispersed pHEMA/AAm-g-LDPE drug release system: In-vitro release kinetics for the treatment of endometriosis

Siddiqa AJ, Shrivastava NK, Ali Mohsin ME, Abidi MH, Shaikh TA, El-Meligy MA

Colloids Surf B Biointerfaces, 2019 Jul 01;179:445-452.
PMID: 31005739 DOI: 10.1016/j.colsurfb.2019.04.014

This paper focuses on the development of a drug delivery system for systemically controlled release of a poorly soluble drug, letrozole. The work meticulously describes the preparation and characterizations of 2-hydroxyethyl methacrylate (HEMA) polymerization onto hydrophilic acrylamide grafted low-density polyethylene (AAm-g-LDPE) surface for targeted drug release system. The surface morphology and thickness measurement of coated pHEMA layer were measured using scanning electron microscopy (SEM). The swelling study was done in deionized (DI) water and simulated uterine fluid (SUF, pH = 7.6). In vitro release of letrozole from the system was performed in SUF. Further, the release kinetics of letrozole from the system was studied using different mathematical models. The results, suggest that the rate of drug release can be altered by varying the concentrations of cross-linker in pHEMA. The optimized sample released 72% drug at the end of 72 h of measurement.

Matched MeSH terms: Cell Survival/drug effects
Anti-proliferative and anti-invasive properties of a purified fraction from Streptomyces sp. H7372

Yip WK, Cheenpracha S, Chang LC, Ho CC, Seow HF

Int J Oncol, 2010 Nov;37(5):1229-41.
PMID: 20878070

Secondary metabolites from actinomycetes especially the genus Streptomyces may be one of the most important sources for novel anticancer agents. A purified fraction from a novel actinomycete strain, Streptomyces sp. H7372, was elucidated in breast cancer cells. We have isolated three purified fractions from a novel strain, Streptomyces sp. H7372. One of the fractions, designated as 31-2, exhibited the strongest growth-inhibitory effect and thereby was selected for further studies. 31-2 exerted a growth-inhibitory effect on a panel of 15 human cancer and 2 non-malignant cell lines. In MCF-7 and MDA-MB-231 breast cancer cells, 31-2 induced a cytostatic (anti-proliferative) effect without causing cytotoxicity (cell death). Our data suggest that the cytostasis resulted from cell cycle arrest at the G1 phase in MCF-7 cells and at the S phase in MDA-MB-231 cells. Western blot analysis demonstrated a modulation of phosphorylation of the Rb and CDC2 proteins and of CDK4, cyclin D1 and cyclin D3 in the 31-2-treated breast cancer cell lines. The protein levels of CDK2, CDK6, and PCNA were not affected by 31-2 treatment. 31-2 also exhibited an anti-invasive effect in MDA-MB-231 cells. However, this effect is not attributed to the modulation of proteolytic activity in MDA-MB-231 cells as the enzymatic degradation of type IV collagen was not affected by 31-2. The 31-2 is a potent cytostatic and anti-invasive agent and modulates the cell cycle pathway. Together, these results will have important implications in searching for novel approaches to treat cancer.

Matched MeSH terms: Cell Survival/drug effects

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