Fabrication and optimization of curcumin-multiwalled carbon nanotube (C-MWCNT) conjugate reinforced electrospun polyacrylonitrile membrane for water treatment applications.

In the recent times, one of the most crucial tasks related to water resources is the treatment of polluted water. This study reports the development of a functionalized nanofibrous membrane with enhanced filtration performance, heavy metal removal, and photocatalytic dye degradation for the effective treatment of contaminated water. The nanofibrous mats were developed by the process of electrospinning using a polymeric solution of polyacrylonitrile (PAN) reinforced with curcumin-multiwalled carbon nanotube (C-MWCNT) conjugate. The experimental trials for membrane fabrication were adapted based on the design of experiments (DoE) approach by making use of the Box-Behnken design (BBD) for a three-variable system, a component of response surface methodology (RSM). The three variable parameters selected for optimization of the electrospinning process were the dopant concentration (in weight percentage), the flow rate (in millilitre per hour), and the spinning time (in hours), respectively, and a total of 15 fibrous membranes were fabricated. The SEM analysis of the fabricated membranes revealed alterations in the surface morphology of the fibrous mats with variations in the electrospinning parameters. The infrared spectrum of the fibrous mats, validated the incorporation C-MWCNT conjugate in PAN, thereby confirming the formation of PAN/C-MWNCNT membrane. The mean flow pore size and breaking force of the PAN/C-MWCNT membranes was also obtained using a universal testing machine (UTM) and porometer, respectively. To choose the best membrane for efficient filtration experiments, the performance of each of the prepared membranes was assessed in terms of solute rejection percentage (SR%), permeate flux (PF), and pure water flux (PWF). The statistical analysis of the assessed parameters in accordance with the membranes prepared was done using the MINITAB software, and the three-dimensional (3D) surface plots were constructed using the STATISTICA software to visualize and validate the relation between each of the electrospinning parameters and the corresponding membrane performance characteristics. Similarly, the potential of the electrospun membranes for efficient heavy metal ion removal and photocatalysis were also tested independently and the optimal electrospinning parameters were determined for the same. Based on the results, it was observed that the PAN/C-MWCNT membranes could serve as potential candidates for the treatment of polluted water.

Evaluating the ameliorative effect of nano bis-demethoxy curcumin analog against extrapulmonary toxicity in rat induced by inhaled multi-walled carbon nanotube.

Carbon nanotubes (CNTs) exposure in human beings through inhalation may affect pulmonary organs and extrapulmonary organs including liver, kidney, brain, spleen, etc. The toxic effects developed as the result of CNTs exposure made us to explore the beneficial effect of nano bis-demethoxy curcumin analog (NBDMCA) towards multi-walled carbon nanotubes (MWCNTs)-induced toxicity in extrapulmonary organs. The current study described the ameliorative effect of NBDMCA against the toxic effects developed by inhaled MWCNTs in the extrapulmonary organs. The rats are exposed to the fixed aerosol concentration of 5 mg/m3 maintained in inhalation exposure chambers MWCNTs for 15 days as per OECD guidelines. After the exposure with MWCNTs, the animals were treated with NBDMCA (5 mg/kg body weight) with different dose frequencies, i.e., 2 doses per week for 1, 2, and 4 weeks. After treatment duration, the blood was drawn from retro-orbital vein and subjected to biochemical and cytokine analysis. Further the animals were euthanized, and the sample tissues were collected and performed oxidative stress and histopathology. The study results revealed that the intravenous administration of NBDMCA suppresses the extrapulmonary toxicity induced by MWCNTs, i.e., annulling the clinical changes and oxidative stress in various extrapulmonary organs at low doses of NBDMCA, evidenced its antioxidant efficacy. Moreover, use of increased doses provides better reduction in toxic symptoms with negligible side effects confirming the dose-dependent efficacy of NBDMCA. Overall, we suggested that NBDMCA may materialize into an effective compound for the reduction of MWCNTs-induced toxicity.

Alternative methods of monitoring emerging contaminants in water: a review.

Anthropogenic activities have steadily increased the release of emerging contaminants (ECs) in aquatic bodies, and these ECs may have adverse effects on humans even at their trace (µg L-1) levels. Their occurrence in wastewater systems is more common, and the current wastewater treatment facilities are inefficient in eliminating many of such persistent ECs. "Gold standard" techniques such as chromatography, mass spectrometry, and other high-resolution mass spectrometers are used for the quantification of ECs of various kinds, but they all have significant limitations. This paper reviews the alternative methods for EC detection, which include voltammetry, potentiometry, amperometry, electrochemical impedance spectroscopy (EIS) based electrochemical methods, colorimetry, surface-enhanced Raman spectroscopy (SERS), fluorescence probes, and fluorescence spectroscopy-based optical techniques. These alternative techniques have several advantages over conventional techniques, including low sample volume, excludes solid phase extraction procedure, high sensitivity, selectivity, portability, reproducibility, rapidity, low cost, and the ability to monitor ECs in real time. This review summarises each of the alternative methods for detecting ECs in water samples and their respective limits of detection (LODs). The sensitivity of each technique varied depending on the type of EC measured, type of electrochemical probe and electrode, substrates, type of nanoparticle (NP), the physicochemical parameters of water samples tested, and more. Nevertheless, this paper also focuses on some of the current challenges encountered by these alternative methods in monitoring ECs.

Toxicity of Graphene: An Update.

Graphene possesses wider biomedical applications including drug delivery, photothermal ablation of tumors, biosensors, and also in the disease diagnosis. The accidental or intentional exposure of the environment including plants, ecosystem, and humans toward graphene is gradually increasing. Therefore, graphene toxicity becomes a critical issue to be addressed despite their diverse applications in multiple fields. In this situation, the scientific community as well as the general public must get awareness about the toxicity of graphene. This article, therefore, reviews the investigations on graphene toxicity. This review reveals the toxicity of graphene in vitro, in vivo models along with the environmental toxicity. The advantages of graphene toxicity in bacterial cells and cancer cells were also reviewed.

Multi-walled carbon nanotube-induced inhalation toxicity: Recognizing nano bis-demethoxy curcumin analog as an ameliorating candidate.

Human beings and ecosystems are being possibly exposed to CNTs, as there is a rise in global production rate of carbon nanotubes (CNTs). This may affect the health of humans and increases the environmental risk. We have already reported the pulmonary toxicity due to the inhalation of MWCNTs. We claim that a compound with anti-inflammatory and antioxidant activity may ameliorate the CNT-induced toxic effect. With this view, we have investigated the ameliorative effect of intravenously-administered nano bis-demethoxy curcumin analog (NBDMCA) against MWCNTs-induced inhalation toxicity by examining the lung histopathology for inflammatory cell dynamics, pulmonary remodeling and estimating the inflammatory biomarkers in the broncho-alveolar lavage fluid. We observed that NBDMCA could ameliorate the injury as evidenced by the decline in the levels of markers of inflammation, cell damage, and the histopathological changes induced by MWCNTs. We conclude that NBDMCA may be used to reduce the risk of MWCNTs-induced inhalation toxicity.

Toxicity of carbon nanotubes: A review.

Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.

Amperometric determination of nitrite using natural fibers as template for titanium dioxide nanotubes with immobilized hemin as electron transfer mediator.

A sensing device was constructed for the amperometric determination of nitrite. It is based on the use of titanium dioxide (TiO2) nanotubes template with natural fibers and carrying hemin acting as the electron mediator. A glassy carbon electrode (GCE) was modified with the hemin/TNT nanocomposite. The electrochemical response to nitrite was characterized by impedance spectroscopy and cyclic voltammetry. An amperometric study, performed at a working potential of + 0.75 V (vs. Ag/AgCl), showed the sensor to enable determination of nitrite with a linear response in the 0.6 to 130 µM concentration range and with a 59 nM limit of detection. Corresponding studies by differential study voltammetry (Ep = 0.75 V) exhibited a linear range from 0.6 × 10-6 to 7.3 × 10-5 M with a limit of detection of 84 nM. The sensing device was applied to the determination of nitrite in spiked tap and lake water samples. Graphical abstract Natural fibers templated synthesis of TNT immobilized hemin as electron transfer mediator for quantitative detection of nitrite with detection limit of 59 nM and good electrochemical sensitivity and the method can be used for quantitative determination of nitrite in water samples.

Towards Intravenous Drug Delivery: Augmenting the Stability and Dispersity of Bis-Demethoxy Curcumin Analog by Bottom-Up Strategy.

Intravenous route is the best strategy to accomplish fastest and highest delivery of drugs. Hydrophobic drugs like curcumin and its analog exhibit disadvantages like low bioavailability, poor absorption and rapid precipitation on intravenous delivery, all leading to its poor therapeutic value. These can be by-passed by enhancing the dispersity, stability and decreasing the size of the drug by nanotization. Thus, with an intention to deliver bis-demethoxy curcumin analog via intravenous route, we have studied the effect of DMSO, ethanol and acetone on the size, size distribution, stability and yield and identified the best solvent in terms of smallest size, narrow size distribution, more stability and high yield of nano bis-demethoxy curcumin analog (NBDMCA). NBDMCA prepared using DMSO showed the lowest mean particle size cum polydispersity index and highest zeta potential when compared to ethanol and acetone. Hence the DMSO based formulation can provide prolonged action and better efficacy at minimal doses. Thus, the DMSO based NBDMCA can emerge as an ideal therapeutic tool for human use.

Characterization of coal fly ash nanoparticles and their induced in vitro cellular toxicity and oxidative DNA damage in different cell lines.

Coal combustion generates considerable amount of ultrafine particles and exposure to such particulate matter is a major health concern in the developing countries. In this study, we collected nano sized coal fly ash (CFA) and characterized them by scanning electron microscope-energy dispersive X-ray analysis (SEM-EDX), particle size analyzer (PSA) and transmission electron microscope (TEM), and investigated its toxicity in vitro using different cell lines. The imaging techniques showed that the coal fly ash nanoparticles (CFA-NPs) are predominately spherical shaped. The analyses have revealed that the CFA-NPs are 7-50 nm in diameter and contain several heavy metals associated with CFA particles. The studies showed significant amount of toxicity in all cell lines on treatment with CFA-NPs. The cytotoxicity and oxidative DNA damage caused by CFA-NPs were determined by inhibition of cellular metabolism (MTT), total intracellular glutathione (GSH), reactive oxygen species (ROS) and DNA fragmentation in cultured cell lines (Chang liver, HS294T and LL29). The cellular metabolism was inhibited in a dose-dependent manner in CFA-NPs treated cell lines. The CFA-NPs induced ROS and decreased the total intracellular glutathione with increased dose. Further, the CFA-NPs treated cells showed severe DNA laddering as a result of DNA fragmentation.

State of the Art Detection System for Curcumin Analog.

In spite of the need for sensing bisdemethoxycurcumin analog (BDMCA), there is no detection system available so far. For the first time, we have demonstrated a sensing system for detecting BDMCA. Initially, chitosan thin films of three different molecular weights (low, average, high) were tested for the conductivity. The high molecular weight chitosan film was found to produce higher conductance and hence, used as the substrate. Addition of BDMCA to this substrate induced a significant conductance change (as revealed by impedance analyzer), making the detection system qualitative. Addition of increasing concentrations of BDMCA produced significantly concomitant increase in the conductivity (observed as decrease in current density as revealed by cyclic voltammetry) making the sensor quantitative. Our results show that this chitosan based electrochemical sensing system can be used for the rapid quantitative detection of BDMCA. As there is no BDMCA sensor available so far, this type of detection is very essential to monitor the pharmacokinetic behavior, the therapeutic dosage, bioavailability and related toxicity of BDMCA in different formulations and samples.

Future of nano bisdemethoxy curcumin analog: guaranteeing safer intravenous delivery.

The present study deals with the toxicity assessment of NBDMCA in vitro using red cell model and in vivo using rat model. Hemolysis was used as toxicity index in red blood cells. Different concentrations of NBDMCA viz., 20, 40, 60, 80, 100µg/ml in PBS were incubated with the red blood cells of rat. NBDMCA was found to induce less than 3% hemolysis in intact erythrocytes which was far lesser than the accepted threshold of 5%. Hematological cum biochemical parameters along with histopathological analysis and hemolysis were used as toxicity indices in rats. Whole blood of the NBDMCA-treated rats and control rats were analyzed for hematological parameters: erythrocyte count, leukocyte count, leukocyte differential count, hemoglobin, hematocrit, mean cell volume (MCV), mean corpuscular hemoglobin (MCH) using fully automated hematology analyzer. All hematological parameters analyzed were within the normal values in both the groups. Plasma samples were analyzed for biochemical parameters including glucose, blood urea nitrogen (BUN), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine (Cre), albumin (Alb), total protein (TP), calcium (Ca) and phosphorus (P) using fully automated biochemistry analyzer. Invariably, all the biochemical parameters are significantly similar in both the groups. Gross examination of vital organs like lung, heart, kidney, spleen and brain reveals no detectable abnormalities in NBDMCA-treated animals. Internal organs like heart, brain, lung, liver, spleen and kidneys of the experimental animals were collected and fixed in 10% formalin, processed in vacuum infiltration tissue processor, embedded with paraffin wax and sectioned at approximately 5µm thick, stained with hematoxylin and eosin. The sections were examined and imaged through light microscopy. NBDMCA did not produce any significant changes in the histoarchitecture of all the organs studied. Heart, aorta, brain, lung, liver, kidney and spleen showed normal pathology report. The histopathological data correlated with the biochemical results indicating normal hepatocellular and nephrotic function. Our investigation clearly revealed that NBDMCA is hemocompatible in vitro and also safe to vital organs in vivo. We conclude that NBDMCA is non-toxic and safe and can be promoted as an ideal therapeutic tool for human use.

One time nose-only inhalation of MWCNTs: Exploring the mechanism of toxicity by intermittent sacrifice in Wistar rats.

We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-α and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure.

Chitosan-starch nanocomposite particles as a drug carrier for the delivery of bis-desmethoxy curcumin analog.

The conventional drug delivery system has serious limitations such as lack of target specificity, altered effects and diminished potency. These limitations can be overcome by using biocompatible polymer as an effective drug delivery system. In this study, bis-demethoxy curcumin analog loaded Chitosan-starch (BDMCA-CS) nanocomposite particles were developed using different ratios of Chitosan and starch (3:1, 1:1 & 1:3) by ionic gelation method. The entrapment efficiency and drug loading capacity were found to be high for the formulation with the ratio 3:1 of BDMCA:CS. Physical characterization of the nanocomposite particles was determined using DLS and FTIR. The morphology of the BDMCA-CS nanocomposite particles were found to be spherical and regular by SEM analysis. In-vitro drug release profile of the BDMCA-CS nanocomposite particles showed a very slow and sustained diffusion controlled release of the drug. The cancer cells targeting ability of the BDMCA-CS nanocomposite particles were confirmed by performing MTT assay on MCF-7 breast cancer cell lines and VERO cell lines.

Effects of ultrafine petrol exhaust particles on cytotoxicity, oxidative stress generation, DNA damage and inflammation in human A549 lung cells and murine RAW 264.7 macrophages.

Air pollution has persistently been the major cause of respiratory-related illness and death. Environmental pollutants such as diesel and petrol exhaust particles (PEPs) are the major contributors to urban air pollution. The aim of the present study was to characterize and investigate the in vitro cytotoxicity, oxidative stress, DNA damage and inflammation induced by PEPs. Cultured type II epithelium cells (human A549 lung cells) and alveolar macrophages (murine RAW 264.7 cells) were exposed to control, vehicle control and to different concentrations of PEPs for up to 24h. Each treatment was evaluated by cell viability, cytotoxicity, oxidative stress, DNA damage and inflammatory parameters. Overall in vitro studies demonstrated that both cell lines showed similar patterns in response to the above studies induced by petrol exhaust nanoparticles (PENPs). Vehicle control showed no changes compared with the control. In both cell lines, significant changes at the dose of 20 and 50µg/mL (A549 cell lines) and 10and 20µg/mL (macrophages) for PENPs were found. The reactive oxygen species production in both cell lines shot up in minutes, reached the maximum within an hour and came down after 4h. Hence, exposure to PENPs resulted in dose-dependent toxicity in cultured A549 cells and RAW 264.7 cells and was closely correlated to increased oxidative stress, DNA damage and inflammation.

Aqueous extract of Trigonella foenum graecum (fenugreek) prevents cypermethrin-induced hepatotoxicity and nephrotoxicity.

Cypermethrin (CM) is an important type II pyrethroid pesticide used extensively in pest control and is reported to cause hepatic and renal toxicity. Oxidative stress and lipid peroxidation (LPO) has been implicated in the toxicology of pyrethroids. Fenugreek is known for its antitoxic and antioxidant potential. We have investigated the protective effect of aqueous extract of germinated fenugreek seeds in CM-induced hepatic and renal toxicity. Male Wistar rats were treated with 1/10 LD(50) (25 mg/kg body weight) of CM and 10% aqueous extract of fenugreek (GFaq) for 60 days. CM treatment caused increased thiobarbituric acid reactive substances (TBARS), depletion in glutathione (GSH) and reduction in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in liver and kidneys. There was a significant reduction in total phospholipids and increased activities of phospholipases A (PLA) and C (PLC) in liver and kidneys and increased activities of serum marker enzymes, aspartate transaminase (AST), alanine tansaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT). Treatment with 10% GFaq showed replenishment of antioxidant status and brought all the values to near normal, indicating the protective effect of fenugreek. Phytochemicals present in fenugreek could play an important role in ameliorating the pesticide-induced toxicity.

Prevention of 1,2-dimethylhydrazine-induced circulatory oxidative stress by bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione during colon carcinogenesis.

We have performed this study to investigate the modulatory effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxy curcumin analog (BDMCA) on circulatory lipid peroxidation (LPO) and antioxidant status during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Wistar rats. The effects were compared with that of the reference drug, curcumin. Increased tumor incidence as well as enhanced LPO in the circulation of tumor bearing rats was accompanied by a significant decrease in the level of reduced glutathione and activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Intragastric administration of BDMCA or curcumin to DMH-treated rats significantly decreased colon tumor incidence and the circulatory LPO, with simultaneous enhancement of GSH content and GPx, GST, SOD and CAT activities. We report that BDMCA exert its chemopreventive effect by decreasing the colon tumor incidence as well as by modulating circulatory oxidative stress in DMH-treated rats through its influence on LPO and antioxidant status. The effects of BDMCA were comparable with that of the reference compound curcumin, a well known anticarcinogen and antioxidant. Thus, it would be suggested that the methoxy group is not responsible for the beneficial effects, however, the terminal phenolic moieties or the central 7-carbon chain may play a role.