Farhat Jabeen

Toxicity of Nano-Titanium Dioxide (TiO2-NP) Through Various Routes of Exposure: a Review.

Nano-titanium dioxide (TiO2) is one of the most commonly used materials being synthesized for use as one of the top five nanoparticles. Due to the extensive application of TiO2 nanoparticles and their inclusion in many commercial products, the increased exposure of human beings to nanoparticles is possible. This exposure could be routed via dermal penetration, inhalation and oral ingestion or intravenous injection. Therefore, regular evaluation of their potential toxicity and distribution in the bodies of exposed individuals is essential. Keeping in view the potential health hazards of TiO2 nanoparticles for humans, we reviewed the research articles about studies performed on rats or other mammals as animal models. Most of these studies utilized the dermal or skin and the pulmonary exposures as the primary routes of toxicity. It was interesting that only very few studies revealed that the TiO2 nanoparticles could penetrate through the skin and translocate to other tissues, while many other studies demonstrated that no penetration or translocation could happen through the skin. Conversely, the TiO2 nanoparticles that entered through the pulmonary route were translocated to the brain or the systemic circulation from where these reached other organs like the kidney, liver, etc. In most studies, TiO2 nanoparticles appeared to have caused oxidative stress, histopathological alterations, carcinogenesis, genotoxicity and immune disruption. Therefore, the use of such materials in humans must be either avoided or strictly managed to minimise risks for human health in various situations.

Orally disintegrating films: A modern expansion in drug delivery system.

Over the past few decades, tendency toward innovative drug delivery systems has majorly increased attempts to ensure efficacy, safety and patient acceptability. As discovery and development of new chemical agents is a complex, expensive and time consuming process, so recent trends are shifting toward designing and developing innovative drug delivery systems for existing drugs. Out of those, drug delivery system being very eminent among pediatrics and geriatrics is orally disintegrating films (ODFs). These fast disintegrating films have superiority over fast disintegrating tablets as the latter are associated with the risks of choking and friability. This drug delivery system has numerous advantages over conventional fast disintegrating tablets as they can be used for dysphasic and schizophrenic patients and are taken without water due to their ability to disintegrate within a few seconds releasing medication in mouth. Various approaches are employed for formulating ODFs and among which solvent casting and spraying methods are frequently used. Generally, hydrophilic polymers along with other excipients are used for preparing ODFs which allow films to disintegrate quickly releasing incorporated active pharmaceutical ingredient (API) within seconds. Orally disintegrating films have potential for business and market exploitation because of their myriad of benefits over orally disintegrating tablets. This present review attempts to focus on benefits, composition, approaches for formulation and evaluation of ODFs. Additionally, the market prospect of this innovative dosage form is also targeted.

Toxic Effects of Titanium Dioxide Nanoparticles and Titanium Dioxide Bulk Salt in the Liver and Blood of Male Sprague-Dawley Rats Assessed by Different Assays

This study evaluated the toxic effects of titanium dioxide (TiO2) bulk salt as well as its nanoparticles (NPs) in anatase phase with mean crystallite size of 36.15 nm in male Sprague-Dawley rats by subcutaneous injections at four different dose levels of either control (0), 50, 100 or 150 mg/kg of body weight (BW) of rat for 28 days on alternate days. Animal mortality, haematology, micronucleus assay, liver histology and activities of liver tissue damage markers like, alkaline phosphate (ALP), alanine transaminase (ALT), aspartate transaminase (AST), as well as oxidative stress indicators like superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH) and lipid peroxidation (LPO) were investigated. The study revealed significant differences (P < 0.05) among control and experimental groups in all the haematological parameters at the end of experiment. Significantly elevated levels (P < 0.05) of ALT, AST and ALP were found for the group treated with TiO2 NPs at the dose of 150 mg/kg of body weight as compared to control. TiO2 and TiO2 NPs caused dose-dependent genotoxicity in the blood cells of the treated rat as revealed bymicronuclei test. The highest frequency of micronuclei was observed in rats treated with NPs at the dose of 150 mg/kg BW which was significantly different (P < 0.001) from all other experimental groups after 28 days of exposure. Similarly, all the treatments showed dose-dependent oxidative stress in the treated rats. However, the significantly high decline in the activities of CAT, SOD, and GST as well as elevation in malondialdehyde and GSH was observed in the group receiving NPs at the rate of 150 mg/kg BW. TiO2 also caused histological alterations in the liver. The study revealed that higher dose of TiO2 NPs exerted significantly harmful effects on liver and blood as compared to its lower doses as well as from all other doses of their bulk counterparts.

Tracing the Bioavailability of Three-Dimensional Graphene Foam in Biological Tissues

Graphene-based materials with a three-dimensional (3D) framework have been investigated for a variety of biomedical applications because of their 3D morphology, excellent physiochemical properties, volume stability, and their controllable degradation rate. Current knowledge on the toxicological implications and bioavailability of graphene foam (GF) has major uncertainties surrounding the fate and behavior of GF in exposed environments. Bioavailability, uptake, and partitioning could have potential effects on the behavior of GF in living organisms, which has not yet been investigated. Here, we report a pilot toxicology study on 3D GF in common carps. Our results showed that GF did not show any noticeable toxicity in common carps, and the antioxidant enzymatic activities, biochemical and blood parameters persisted within the standard series. Further histological imaging revealed that GF remained within liver and kidney macrophages for 7 days without showing obvious toxicity. An in vivo study also demonstrated a direct interaction between GF and biological systems, verifying its eco-friendly nature and high biocompatibility.

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg−1) and high (15 mg kg−1) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin–eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities

Fraxinus, a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications.

Effect of Heavy Metals on Liver, Kidney, Gills and Muscles of Cyprinus carpio and Wallago attu inhabited in the Indus

The present study was aimed to evaluate the effect of heavy metals on an important tissue of two fish species Cyprinus carpio and Wallago attu, sampled from the Indus river, Mianwali District, Pakistan. The concentration of selected heavy metals Fe, Cr, Cu, and in gills, muscles, kidney and liver was compared with an International standard of food fish. The overall metal concentrations among different weight categories in C. carpio were in the order of Fe > Cu > Cr >. In W. attu the overall accumulation of these metals were, in order of Fe > Cu > Cr > Pb The order of accumulation of metals in gills and muscle of C. carpio was Fe > Cr > Pb > Cu; kidney and muscles of W. attu was Fe > Cr > Cu > Pb; liver Fe > Cu > Cr > Pb. An increasing trend of concentration of iron, copper, chromium and lead occurred with an increase in weight of C. carpio and W. attu. There was a significant difference in the accumulation of heavy metals in different organs of both species (p<0.01). All studied heavy metals except Cr were within permissible limits described by various international agencies like WHO, FAO and FEPA in edible tissues of C. carpio and W. attu.

Astragalin: A Bioactive Phytochemical with Potential Therapeutic Activities

Natural products, an infinite treasure of bioactive chemical entities, persist as an inexhaustible resource for discovery of drugs. This review article intends to emphasize on one of the naturally occurring flavonoids, astragalin (kaempferol 3-glucoside), which is a bioactive constituent of various traditional medicinal plants such as Cuscuta chinensis. This multifaceted compound is well known for its diversified pharmacological applications such as anti-inflammatory, antioxidant, neuroprotective, cardioprotective, antiobesity, antiosteoporotic, anticancer, antiulcer, and antidiabetic properties. It carries out the aforementioned activities by the regulation and modulation of various molecular targets such as transcription factors (NF-κB, TNF-α, and TGF-β1), enzymes (iNOS, COX-2, PGE2, MMP-1, MMP-3, MIP-1α, COX-2, PGE-2, HK2, AChe, SOD, DRP-1, DDH, PLCγ1, and GPX), kinases (JNK, MAPK, Akt, ERK, SAPK, IκBα, PI3K, and PKCβ2), cell adhesion proteins (E-cadherin, vimentin PAR-2, and NCam), apoptotic and antiapoptotic proteins (Beclin-1, Bcl-2, Bax, Bcl-xL, cytochrome c, LC3A/B, caspase-3, caspase-9, procaspase-3, procaspase-8, and IgE), and inflammatory cytokines (SOCS-3, SOCS-5, IL-1β, IL-4, IL-6, IL-8, IL-13, MCP-1, CXCL-1, CXCL-2, and IFN-γ). Although researchers have reported multiple pharmacological applications of astragalin in various diseased conditions, further experimental investigations are still mandatory to fully understand its mechanism of action. It is contemplated that astragalin could be subjected to structural optimization to ameliorate its chemical accessibility, to optimize its absorption profiles, and to synthesize its more effective analogues which will ultimately lead towards potent drug candidates.

Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio

Recently, Cu-based nanoparticles have drawn considerable attention for their various fascinating roles in multiple biological systems. It is recognized that their frequent use can create compatibility challenges for the recipient systems. Nevertheless, it is unclear how various biological interactions affect the compatibility of Cu oxide II (CuO) and Cu oxide nanoparticles (Cu-NPs) for different organisms. Consequently, it has been difficult to perform structured risk assessments for their use in biological systems. Therefore, this study compared the effects of different doses of waterborne Cu-NPs and CuO on the blood and liver of selected groups of Cyprinus (C) carpio. These fish while housed in suitable water tanks were exposed to one of the following treatments for 14 d: control (no added Cu) or 0.5 or 1 or 1.5 mg Cu as Cu-NPs or CuO l-1 of water. We found significant changes in all assessed blood parameters of fish in response to increasing doses from 0 to 1.5 mg of Cu-NPs or CuO. Similarly, increased levels of lipid peroxide and reduced glutathione (GSH) were also observed in the livers of C. carpio in Cu-NPs or CuO treated groups. Enhanced levels of lipid peroxidation and GSH were also recorded in the Cu-NP treated groups compared with the CuO treated groups in a dose dependent manner. The lowest catalase activity was observed in the liver of C. carpio treated with the higer dose of Cu-NPs. Cu-NP or CuO exposure induced significant histological alterations in the liver of C. carpio including focal necrosis, cloudy swelling of hepatocytes, degenerative hepatocytes, vacuolization, pyknotic nuclei, damaged central vein, nuclear hypertrophy, dilated sinusoid, vacuolated degeneration, congestion, and complete degeneration in a dose dependent manner. Substantial alterations in blood and liver specimens were observed in the Cu-NP treated fish when compared with the CuO treated fish. It appeared that the Cu-NPs were more toxic than the CuO as shown by the hemato- and hepatotoxicity in C. carpio of this study.

Ameliorative effects of Moringa oleifera on copper nanoparticle induced toxicity in Cyprinus carpio assessed by histology and oxidative stress markers

Nanoparticles (NPs) enter the environment mainly through waste water effluents, accidental spillage, and industrial runoffs. This is worrying because NPs can enter the human body owing to their large aspect-to-size ratio and reactive surfaces that facilitate their penetration through biological barriers and thus can induce oxidative stress in host cells. Therefore, there is a growing concern about the toxicity of NPs, which needs to be addressed. Thus, this study investigated the ameliorative effects of Moringa oleifera seed extract (MOSE) in Cyprinus carpio exposed to copper nanoparticles (Cu-NPs). For the in vivo assessment of the shielding effects of MOSE, 240 samples of C. carpio (40-45 g) were randomly allocated to 24 experimental tanks (10 fish/tank of 40 L) 24 h prior to the start of this experiment. The experimental fish were faced with the water-born exposure of a pre-determined dose of 1.5 mg Cu-NPs/l along with pre- and post-treatment with different doses (100 or 200 or 300 mg l-1) of MOSE for 28 days. The MOSE showed significant ameliorative effect on the antioxidant defense, in response to the elevated levels of Cu-NP-induced oxidative stress. It also played a protective role as indicated by the suppression of the histological alterations in the gills and liver of fish exposed to the Cu-NPs. It was concluded that the Cu-NP-induced toxicity in C. carpio was ameliorated by the use of MOSE in this study. Moreover, the post-Cu-NP treatment stage showed more protective effects of MOSE than the pre-Cu-NP treatment phase. Further studies are suggested to determine the optimum dose and delivery method of MOSE for similar or different NP exposed fish.