The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.
Artemisinin (ART) is an antimalarial compound that possesses a variety of novel biological activities. Due to the low abundance of ART in natural sources, agricultural supply has been erratic, and prices are highly volatile. While heterologous biosynthesis and semi-synthesis are advantageous in certain aspects, these approaches remained disadvantageous in terms of productivity and cost-effectiveness. Therefore, further improvement in ART production calls for approaches that should supplement the agricultural production gap, while reducing production costs and stabilising supply. The present review offers a discussion on the elicitation of plants and/or in vitro cultures as an economically feasible yield enhancement strategy to address the global problem of access to affordable ART. Deemed critical for the manipulation of biosynthetic potential, the mechanism of ART biosynthesis is reviewed. It includes a discussion on the current biotechnological solutions to ART production, focusing on semi-synthesis and elicitation. A brief commentary on the possible aspects that influence elicitation efficiency and how oxidative stress modulates ART synthesis is also presented. Based on the critical analysis of current literature, a hypothesis is put forward to explain the possible involvement of enzymes in assisting the final non-enzymatic transformation step leading to ART formation. This review highlights the critical factors limiting the success of elicitor-induced modulation of ART metabolism, that will help inform strategies for future improvement of ART production. Additionally, new avenues for future research based on the proposed hypothesis will lead to exciting perspectives in this research area and continue to enhance our understanding of this intricate metabolic process.
The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.
Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target.
Binary blends of palm olein (PO) with sunflower oil (SFO), canola oil (CNO), and cottonseed oil (CSO) were formulated to assess their stability under continuous frying conditions. The results were then compared with those obtained in PO. The oil blends studied were: (1) 60:40 for PO + SFO; (2) 70:30 for PO + CNO; and (3) 50:50 for PO + CSO. The PO and its blends were used to fry potato chips at 180°C for a total of 56 h of operation. The evolution of analytical parameters such as tocols, induction period, color, p-anisidine value, free fatty acid, smoke point, polar compounds, and polymer compounds were evaluated over the frying time. Blending PO with unsaturated oils was generally proved to keep most qualitative parameters comparable to those demonstrated in PO. Indeed, none of the oils surpassed the legislative limits for used frying. Overall, it was noted that oil containing PO and SFO showed higher resistance toward oxidative and hydrolytic behaviors as compared to the other oil blends.
Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin-type fungal secondary metabolites is in part generated by a trans to cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S-transferase PsoE requires participation of the bifunctional C-methyltransferase/epoxidase PsoF to complete the trans to cis isomerization of the pathway intermediate presynerazol. The crystal structure of the PsoE/glutathione/presynerazol complex indicated stereospecific glutathione-presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, thus making it a trifunctional enzyme which is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans to cis isomerization reaction.
Genetic aberrations have been identified in nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains elusive. There are increasing evidences that the apoptotic nuclease caspase-activated deoxyribonuclease (CAD) is one of the players leading to translocation in leukemia. Oxidative stress, which has been strongly implicated in carcinogenesis, is a potent apoptotic inducer. Most of the NPC etiological factors are known to induce oxidative stress. Although apoptosis is a cell death process, cells possess the potential to survive apoptosis upon DNA repair. Eventually, the surviving cells may carry rearranged chromosomes. We hypothesized that oxidative stress-induced apoptosis may cause chromosomal breaks mediated by CAD. Upon erroneous DNA repair, cells that survive apoptosis may harbor chromosomal rearrangements contributing to NPC pathogenesis. This study focused on the AF9 gene at 9p22, a common deletion region in NPC. We aimed to propose a possible model for molecular mechanism underlying the chromosomal rearrangements in NPC.
Copper ion recognition and DNA interaction of a newly synthesized fluorescent Schiff base (HPyETSC) were investigated using UV-vis and fluorescent spectroscopy. Examination using these two techniques revealed that the detection of copper by HPyETSC is highly sensitive and selective, with a detection limit of 0.39 μm and the mode of interaction between HPyETSC and DNA is electrostatic, with a binding constant of 8.97×10(4) M(-1). Furthermore, gel electrophoresis studies showed that HPyETSC exhibited nuclease activity through oxidative pathway.
Solution-enhanced dispersion by supercritical carbon dioxide (SEDS) and spray drying (SD) were used to microencapsulate red palm oil (RPO) to prolong the functionality of carotenes and vitamin E. The protective effects provided by SEDS and SD were evaluated in terms of the oxidative stability (65 °C for 35 days), fatty acid compositions, color change and degradation kinetics of carotenes and vitamin E (25 °C, 45 °C, 65 °C, and 85 °C for up to 198 days). SEDS microcapsules (SEDS-M) were the most oxidatively stable (total oxidation (Totox): 26.5), followed by SD microcapsules (SD-M) (34.9) and RPO (56.7). Degradation of carotenes and vitamin E fitted well a first-order kinetic model (average absolute relative deviation = 2-16%). SEDS-M offered better protection to vitamin E (Ea = 36 kJ/mol), whereas SD-M provided better protection for α + β carotene (Ea = 29 kJ/mol). Overall, encapsulation protected RPO during storage, with SEDS-microencapsulated RPO performing better than SD-microencapsulated RPO.
The chlorine radical is a potent atmospheric oxidant, capable of perturbing tropospheric oxidative cycles normally controlled by the hydroxyl radical. Significantly faster reaction rates allow chlorine radicals to expedite oxidation of hydrocarbons, including methane, and in polluted environments, to enhance ozone production. Here we present evidence, from the CARIBIC airborne dataset, for extensive chlorine radical chemistry associated with Asian pollution outflow, from airborne observations made over the Malaysian Peninsula in winter. This region is known for persistent convection that regularly delivers surface air to higher altitudes and serves as a major transport pathway into the stratosphere. Oxidant ratios inferred from hydrocarbon relationships show that chlorine radicals were regionally more important than hydroxyl radicals for alkane oxidation and were also important for methane and alkene oxidation (>10%). Our observations reveal pollution-related chlorine chemistry that is both widespread and recurrent, and has implications for tropospheric oxidizing capacity, stratospheric composition and ozone chemistry.
In this paper, a facile synthesis method for CaFe2O4 is introduced that produces a catalyst capable of significant photocatalytic degradation of POME under visible light irradiation. The co-precipitation method was used to produce two catalysts at calcination temperatures of 550 °C and 700 °C dubbed CP550 and CP700. CP550 demonstrated the maximum COD removal of 69.0% at 0.75 g/L catalyst loading after 8 h of visible light irradiation which dropped to 61.0% after three consecutive cycles. SEM images indicated that the higher calcination temperature of CP700 led to annealing which reduced the pore volume (0.025 cm3/g) and pore diameter (10.3 nm) while simultaneously creating a smoother and more spherical surface with lower SBET (9.73 m2/g). In comparison, CP550 had a rough hair-like surface with higher SBET (27.28 m2/g) and pore volume (0.077 cm3/g) as evidenced by BET analysis. XRD data indicated the presence of CaFe5O7 in the CP550 composition which was not present in CP700. The presence of Wustite-like FeO structures in CaFe5O7 are likely the cause for lower photoluminescence intensity profile and hence better charge separation of CP550 as these structures in CaFe2O4 have been known to increase resistivity and electron localization. The COD removal of CP550 dropped from 69.0% to just 7.0% upon adding a small quantity of isopropanol into the reaction mixture indicating hydroxyl radicals as the primary reactive oxidative species.
The objective of this study was to optimize the extraction of oil from pre-dried roselle seeds using response surface methodology (RSM). We also determined the oxidative stability of oil extracted from oven and freeze-dried roselle seed in terms of iodine value (IV), free fatty acid (FFA) value, peroxide value (PV), P-anisidine and total oxidation values (TOTOX value). The RSM was designated based on the central composite design with the usage of three optimum parameters ranged from 8 to 16 g of sample weight, 250-350 mL of solvent volume, and 6-8 h of extraction time. The highest oil yielded from roselle seed using the optimization process was 22.11% with the parameters at sample weight of 14.4 g, solvent volume of 329.70 mL, and extraction time of 7.6 h. Besides, the oil extracted from the oven dried roselle seed had the values of 89.04, 2.11, 4.13, 3.76 and 12.03 for IV, FFA, PV, P-anisidine, and TOTOX values, respectively. While for the oil extracted from freeze-dried roselle seed showed IV of 90.31, FFA of 1.64, PV of 2.47, P-anisidine value of 3.48, and TOTOX value of 8.42. PV and TOTOX values showed significant differences whereas; IV, FFA, and P-anisidine values showed no significant differences between the oven and freeze-dried roselle seed oils.
Prostate cancer has become the second leading cancer in men worldwide. Androgen plays an important role in normal functioning, development, and differentiation of the prostate, and thus is considered to be the most powerful candidate that mediates reactive oxygen species (ROS) balance in the prostate. The elevation of ROS has been associated with the progression and development of this disease. Conventional therapy has shown a high cure rate in patients with localized prostate cancer. Despite the patients respond favorably initially, this therapy fails to response in the advanced stage of the diseases even in the absence of androgens. Indeed, the onset and progression of prostate cancer could be prevented by changing dietary habits. Much information indicates that oxidative stress and prostate cancer can be modulated by dietary components rich in antioxidants. While there is substantial evidence to suggest an association between prostate cancer risk and ROS-mediated oxidative stress; therefore, the interactions and mechanisms of this phenomenon are worth to discuss further. This review aimed to discuss the mechanisms of action of oxidative stress involved in the progression of prostate cancer. We also highlighted how some of the vital dietary components dampen or exacerbate inflammation, oxidative stress, and prostate cancer. Overall, the reported information would provide a useful approach to the prevention of prostate cancer.
Selective logging is the dominant form of human disturbance in tropical forests, driving changes in the abundance of vertebrate and invertebrate populations relative to undisturbed old-growth forests. A key unresolved question is understanding which physiological mechanisms underlie different responses of species and functional groups to selective logging. Regulation of oxidative status is thought to be one major physiological mechanism underlying the capability of species to cope with environmental changes. Using a correlational cross-sectional approach, we compared a number of oxidative status markers among 15 understorey bird species in unlogged and selectively logged forest in Borneo in relation to their feeding guild. We then tested how variation of markers between forest types was associated with that in population abundance. Birds living in logged forests had a higher activity of the antioxidant enzyme superoxide dismutase and a different regulation of the glutathione cycle compared to conspecific birds in unlogged forest. However, neither oxidative damage nor oxidized glutathione differed between forest types. We also found that omnivores and insectivores differed significantly in all markers related to the key cellular antioxidant glutathione irrespective of the forest type. Species with higher levels of certain antioxidant markers in a given type of forest were less abundant in that forest type compared to the other. Our results suggest that there was little long-term effect of logging (last logging rotation occurred ~15 years prior to the study) on the oxidative status of understorey bird species. However, it is unclear if this was owing to plasticity or evolutionary change. Our correlative results also point to a potential negative association between some antioxidants and population abundance irrespective of the forest type.
The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today's society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation.
Alzheimer's disease (AD) is a fatal neurodegenerative disease that requires immediate attention. Oxidative stress that leads to the generation of reactive oxygen species is a contributing factor to the disease progression by promoting synthesis and deposition of amyloid-β, the main hallmark protein in AD. It has been previously demonstrated that nanoyttria possesses antioxidant properties and can alleviate cellular oxidative injury in various toxicity and disease models. This review proposed that nanoyttria could be used for the treatment of AD. In this paper, the evidence on the antioxidant potential of nanoyttria is presented and its prospects on AD therapy are discussed.
Encapsulating fish oil by spray drying with an adequate wall material was investigated to determine if stable powders containing emulsified fish-oil-droplets can be formed. In particular, the dextrose equivalent (DE) of maltodextrin (MD) affects the powder structure, surface-oil ratio, and oxidative stability of fish oil. The carrier solution was prepared using MD with different DEs (DE = 11, 19, and 25) and sodium caseinate as the wall material and the emulsifier, respectively. The percentage of microcapsules having a vacuole was 73, 39, and 38% for MD with DE = 11, 19, and 25, respectively. Peroxide values (PVs) were measured for the microcapsules incubated at 60 °C. The microcapsules prepared with MD of DE = 25 and 19 had lower PVs than those prepared with MD of DE = 11. The difference in PV can be ascribed to the difference in the surface-oil ratio of the spray-dried microcapsules.
Kenaf seed oil-in-water nanoemulsions (KSON) and kenaf seed oil-in-water macroemulsions were produced to access their gastroprotective effect against indomethacin- and ethanol-induced ulcers in comparison with non-emulsified kenaf seed oil (KSO). Emulsifier mixture (EM) that used to emulsify KSO was also included in the study. Ulcer index, stomach tissue oxidative status, and histopathological changes in indomethacin-induced and ethanol-induced ulcer models were both evaluated. KSON had demonstrated good gastroprotective effect against both ulcer models than non-emulsified KSO and KSOM. In addition, the gastroprotective effect of KSON was comparable to the standard drug, Omeprazole. EM also exhibited gastroprotective effect, especially in indomethacin-induced ulcers. This may be attributed to its high antioxidant activity and cytoprotective effect of sodium caseinate contained in the EM. Results supported that KSON enhanced the bioavailability of native KSO; therefore it offers gastroprotective effect for the prevention of gastric ulceration as a natural alternative to the synthetic drug.
N-Methyl-3, 4-methylenedioxyamphetamine (MDMA), or ecstasy is a recreational drug of abuse. It is a synthetic substance that affects the body's systems, which its mechanism of action and treatment should be more investigated. MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure. Only a few studies have been done regarding its treatment. Thus, the treatment of MDMA complications should be further explored mainly by targeting its mechanism of action in the neurotransmitter systems. Hence, this study presents a short review regarding the recent findings on the role of neurotransmitters to cause MDMA neurotoxicity. The results will be useful for future research in elucidating the potential treatment based on the targeted mechanisms to treat the neurotoxic effects of MDMA.
Pharmaceutical delivery systems are developed to improve the physicochemical properties of therapeutic compounds. Emulsions are one of these drug delivering systems formulated using water, oils and lipids as main ingredients. Extensive data are usually generated on the physical and chemical characteristics of these oil-in-water and lipid emulsions. However, the oxidative tendency of emulsions is often overlooked. Oxidation impacts the overall quality and safety of these pharmaceutical emulsions. Additionally, introducing oxidatively unstable emulsions into biological systems further promotes oxidation in situ. Products of these reactions then continue to pose serious harm to cells and fuel other physiological oxidation reactions. Consequently, the increase of oxidation products leads to oxidative damage to biological systems. Thus, emulsions with lower lipid peroxidation are more stable and will reduce the negative effects of oxidation in situ. Preventive measures during the formulation of emulsions are important. Many naturally occurring and cost effective substances possess low oxidation tendencies and confer oxidative protection when used in emulsions. Additionally, certain preparatory methods should be employed to reduce or better control lipid peroxidation. Finally, emulsions must be evaluated for their oxidation susceptibility using the various techniques available. Careful attention to the preparation of emulsions and assessment of their oxidative stability will help produce safer emulsions without compromising efficacy.