scholarly journals Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Andreanne G. Vasconcelos ◽  
Ana Luisa A. N. Barros ◽  
Wanessa F. Cabral ◽  
Daniel C. Moreira ◽  
Ingrid Gracielle M. da Silva ◽  
...  

Abstract Background Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated. Results NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability. Conclusions Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products. Graphical Abstract

2016 ◽  
Vol 2 (12) ◽  
pp. e1600516 ◽  
Author(s):  
Paulo R. F. Rocha ◽  
Maria C. R. Medeiros ◽  
Ulrike Kintzel ◽  
Johannes Vogt ◽  
Inês M. Araújo ◽  
...  

Glioma patients often suffer from epileptic seizures because of the tumor’s impact on the brain physiology. Using the rat glioma cell line C6 as a model system, we performed long-term live recordings of the electrical activity of glioma populations in an ultrasensitive detection method. The transducer exploits large-area electrodes that maximize double-layer capacitance, thus increasing the sensitivity. This strategy allowed us to record glioma electrical activity. We show that although glioma cells are nonelectrogenic, they display a remarkable electrical burst activity in time. The low-frequency current noise after cell adhesion is dominated by the flow of Na+ions through voltage-gated ion channels. However, after an incubation period of many hours, the current noise markedly increased. This electric bursting phenomenon was not associated with apoptosis because the cells were viable and proliferative during the period of increased electric activity. We detected a rapid cell culture medium acidification accompanying this event. By using specific inhibitors, we showed that the electrical bursting activity was prompted by extracellular pH changes, which enhanced Na+ion flux through the psalmotoxin 1–sensitive acid-sensing ion channels. Our model of pH-triggered bursting was unambiguously supported by deliberate, external acidification of the cell culture medium. This unexpected, acidosis-driven electrical activity is likely to directly perturb, in vivo, the functionality of the healthy neuronal network in the vicinity of the tumor bulk and may contribute to seizures in glioma patients.


ChemPlusChem ◽  
2014 ◽  
Vol 79 (8) ◽  
pp. 1083-1088 ◽  
Author(s):  
Uschi M. Graham ◽  
Michael T. Tseng ◽  
Jacek B. Jasinski ◽  
Robert A. Yokel ◽  
Jason M. Unrine ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. M. Saleh ◽  
K. P. Lawrence ◽  
S. A. Jones ◽  
A. R. Young

AbstractUVA1 radiation (340–400 nm), especially longwave UVA1 (> 370 nm), is often ignored when assessing sun protection due to its low sunburning potential, but it generates reactive oxygen species (ROS) and is poorly attenuated by sunscreens. This study aimed to investigate if α-tocopherol phosphate, (α-TP) a promising new antioxidant, could protect against long-wave UVA1 induced cell death and scavenge UVA1 induced ROS in a skin cell model. HaCaT keratinocyte cell viability (24 h) was assessed with Alamar Blue and Neutral Red assays. The metabolism of α-TP into α-T, assessed using mass spectrometry, and the compound's radical scavenging efficacy, assessed by the dichlorodihydrofluorescein (H2DCFDA) ROS detection assay, was monitored in HaCaTs. The mechanism of α-TP ROS scavenging was determined using non-cell based DPPH and ORAC assays. In HaCaT keratinocytes, irradiated with 226 J/cm2 UVA1 in low-serum (2%, starved) cell culture medium, pretreatment with 80 µM α-TP significantly enhanced cell survival (88%, Alamar Blue) compared to control, whereas α-T pre-treatment had no effect survival (70%, Alamar Blue). Pre-treatment of cells with 100 μM α-TP or 100 μM α-T before 57 J/cm2 UVA1 also significantly reduced ROS generation over 2 h (24.1% and 23.9% respectively) compared to the control and resulted in α-TP bioconversion into α-T. As α-TP displayed weak antioxidant activity in the cell-free assays thus its photoprotection was assigned to its bioconversion to α-T by cellular phosphatases. Through this mechanism α-TP prevented long-wave UVA1 induced cell death and scavenged UVA1 induced ROS in skin cells when added to the starved cell culture medium before UVA1 exposure by bioconversion into α-T.


2018 ◽  
Vol 16 (3) ◽  
pp. 143-153 ◽  
Author(s):  
Naymul KARIM ◽  
Lanchakon CHANUDOM ◽  
Jitbanjong TANGPONG

Hyperglycemia is well-known for inducing cellular oxidative damage in type II diabetes (T2D) patients. This research addressed the cytoprotective and anti-genotoxic effect of xanthone derivatives from Garcinia mangostana against hydrogen peroxide (H2O2)-induced human peripheral blood mononuclear cell (PBMC) and blood leukocytes damage of the normal and T2D volunteers. The cytoprotective effects of an aqueous extract of xanthone (100 and 200 µg/mL) was assessed on cell viability and free radical scavenging activity using the trypan blue exclusion method on PBMC cells. Malondialdehyde (MDA) levels and lactate dehydrogenase (LDH) activity were measured as cellular oxidative damage markers and estimated from culture medium of PBMCs of normal and T2D volunteers. The anti-genotoxicity was assessed as the protective effect of xanthone against H2O2-induce DNA damage of blood leukocytes of the normal volunteers following comet assay technique. Xanthone and Gallic acid (control) concentrations 100, 200 and 100 µg/mL significantly (P < 0.05) protected from H2O2 (20 mM)-induced oxidative damage of PBMCs. It was confirmed by increased cell viability and free radical scavenging activity coupled with the decreased MDA and LDH levels in cell culture medium compared to H2O2 (20 mM)-treated group. In H2O2 (40 mM)-induced blood leukocytes of normal volunteers, different concentration xanthone (50 - 500 µg/mL) significantly (P < 0.05) improved the anti-genotoxicity effect compared to negative/positive control group by lowering comet formation. Xanthone treatments on PBMCs and blood leukocytes of the normal and T2D volunteers could attenuate the H2O2-induced cellular oxidative damage and cell death via exhibiting antioxidant and free radical scavenging activities.


INDIAN DRUGS ◽  
2019 ◽  
Vol 56 (07) ◽  
pp. 69-75
Author(s):  
S Parashar ◽  
V. Uplanchiwar ◽  
R. K. Gautam ◽  
S. Goyal ◽  

Ziziphus rugosa Lam. belongs to the family Rhamnaceae and is found chiefly in deciduous and semi evergreen forest of Western Ghats. The present research was undertaken to establish in vitro antioxidant and in vivo hepatoprotective activity of ethanolic extract of Z.rugosa Lam. leaves. The powdered leaves of Z. rugosa were extracted with ethanol and preliminary phytochemical screening was performed for the presence of various phytoconstituents. DPPH assay and β-glucuronidase inhibition assay were selected for the free radical scavenging activity. For the assessment of hepatoprotective activity, alcohol and CCl4 induced hepatotoxicity model were used. The phytochemical analysis of ethanolic extract showed the presence of alkaloids, saponins and flavonoids. The extract exhibited concentration dependent radical scavenging activity with an IC50 value of 61.88 μg/ml and β –glucoronidase inhibition activity with an IC50 value of 70.61 μg/ml. It was speculated that the Z. rugosa Lam. ethanolic extract shows dosedependent hepatoprotective activity which is equivalent with the standard drug Silymarin. The inhibition of free radicals or free radical scavenging activity is significant in the protection against CCl4 and alcohol induced hepatopathy. Hence, it is likely that the antioxidant activity of ethanolic extract of Z. rugosa Lam. might contribute to the hepatoprotective action.


2013 ◽  
Vol 72 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Milena Nikolova ◽  
Mariya Petrova ◽  
Ely Zayova

Abstract Arnica montana L. is an endangered species rich in sesquiterpene lactones, phenolic acids and flavonoids with high pharmaceutical value. The polyphenolic content and free radical scavenging activity of plants that had passed all stages of cultivation: micropropagation and rooting (in vitro), adaptation in greenhouse (ex vitro) and mountain conditions (in vivo) were evaluated. Four surface flavonoid aglycones [scutellarein 6-methyl ether (hispidulin), scutellarein 6,4’-dimethyl ether (pectolinarigenin), 6-OH luteolin 6-methyl ether and kempferol-6-methyl ether] were detected in the acetone exudates of the studied samples bymeans of thin layer chromatography.No differences in the accumulation of surface flavonoids were found among the tested leaf extracts of in vitro, ex vitro and in vivo samples. However, the extracts from the flowers were richer in surface flavonoids than extracts from the leaves. The methanol extracts of the samples from ex vitro and in vivo grown A. montana plants had significantly higher radical scavenging activity and polyphenolic content than the extracts of in vitro samples. The observed differences in the contents of these biologically active compounds were related to different growth conditions and stages of plant development. The biotechnological method of A. montana established holds promise for the future production of antioxidants.


2005 ◽  
Vol 288 (6) ◽  
pp. E1277-E1283 ◽  
Author(s):  
Danielle A. Dufner ◽  
Ilya R. Bederman ◽  
Daniel Z. Brunengraber ◽  
Nadia Rachdaoui ◽  
Faramarz Ismail-Beigi ◽  
...  

We previously reported that 2H2O can be used to measure rates of protein synthesis during prolonged steady-state conditions (Previs SF, Fatica R, Chandramouli V, Alexander JC, Brunengraber H, and Landau BR. Am J Physiol Endocrinol Metab 286: E665-E672, 2004). The underlying premise of our method is that following the administration of 2H2O, 2H atoms in body water rapidly equilibrate with free alanine before it is incorporated into newly synthesized proteins. We have now directly examined whether 2H2O can be used to measure the influence of a single meal on protein synthesis. In addition, we have compared the use of 2H2O for measuring rates of protein synthesis in vivo vs. in cell culture. Using a rat model, we observed rapid equilibration between 2H in body water and free alanine; therefore we were able to study the response of protein synthesis to a single meal. We observed that ∼50% of the plasma albumin that is synthesized over the course of 24 h is made within ∼5 h after eating (in rats trained to eat a complete 24-h ration of food in a single meal). Contrary to what we observed in vivo, feeding (the replenishment of cell culture medium) does influence the use of 2H2O for in vitro studies. In particular, since there can be slow equilibration of 2H between water and alanine in the cell culture medium, special consideration must be made to avoid underestimating the rate of protein synthesis in vitro.


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