The noteworthy intensification in the development of nanotechnology has led to the development of various types of nanoparticles. The diverse applications of these nanoparticles make them desirable candidate for areas such as drug delivery, coasmetics, medicine, electronics, and contrast agents for magnetic resonance imaging (MRI) and so on. Iron oxide magnetic nanoparticles are a branch of nanoparticles which is specifically being considered as a contrast agent for MRI as well as targeted drug delivery vehicles, angiogenic therapy and chemotherapy as small size gives them advantage to travel intravascular or intracavity actively for drug delivery. Besides the mentioned advantages, the toxicity of the iron oxide magnetic nanoparticles is still less explored. For in vivo applications magnetic nanoparticles should be nontoxic and compatible with the body fluids. These particles tend to degrade in the body hence there is a need to understand the toxicity of the particles as whole and degraded products interacting within the body. Some nanoparticles have demonstrated toxic effects such inflammation, ulceration, and decreases in growth rate, decline in viability and triggering of neurobehavioral alterations in plants and cell lines as well as in animal models. The cause of nanoparticles’ toxicity is attributed to their specific characteristics of great surface to volume ratio, chemical composition, size, and dosage, retention in body, immunogenicity, organ specific toxicity, breakdown and elimination from the body. In the current review paper, we aim to sum up the current knowledge on the toxic effects of different magnetic nanoparticles on cell lines, marine organisms and rodents. We believe that the comprehensive data can provide significant study parameters and recent developments in the field. Thereafter, collecting profound knowledge on the background of the subject matter, will contribute to drive research in this field in a new sustainable direction.

Graphene and its oxide are nanomaterials considered currently to be very promising because of their great potential applications in various industries. The exceptional physiochemical properties of graphene, particularly thermal conductivity, electron mobility, high surface area, and mechanical strength, promise development of novel or enhanced technologies in industries. The diverse applications of graphene and graphene oxide (GO) include energy storage, sensors, generators, light processing, electronics, and targeted drug delivery. However, the extensive use and exposure to graphene and GO might pose a great threat to living organisms and ultimately to human health. The toxicity data of graphene and GO is still insufficient to point out its side effects to different living organisms. Their accumulation in the aquatic environment might create complex problems in aquatic food chains and aquatic habitats leading to debilitating health effects in humans. The potential toxic effects of graphene and GO are not fully understood. However, they have been reported to cause agglomeration, long-term persistence, and toxic effects penetrating cell membrane and interacting with cellular components. In this review paper, we have primarily focused on the toxic effects of graphene and GO caused on aquatic invertebrates and fish (cell line and organisms). Here, we aim to point out the current understanding and knowledge gaps of graphene and GO toxicity.

Pathologic hyperreactive inflammatory responses occur when there is excessive activation of a proinflammatory NF-κB pathway and a reduced cytoprotective NRF2 cascade. The noncytotoxic, highly selective COX-2 inhibitory flavonol-enriched butanol fraction (UaB) from Uvaria alba (U. alba) was investigated for its inflammatory modulating potential by targeting NF-κB activation and NRF2 activity. Enzyme-linked immunosorbent assay was initially performed to measure levels of proinflammatory mediators [nitric oxide (NO), prostaglandin E₂, and reactive oxygen species (ROS)] and cytokines [tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6], followed by reverse transcription-polymerase chain reaction and western blotting to determine mRNA and protein expression, respectively. Using immunofluorescence staining combined with western blot analysis, the activation of NF-κB was further investigated. NRF2 activity was also measured using a luciferase reporter assay. UaB abrogated protein and mRNA expressions of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages, thereby suppressing the production of proinflammatory mediators and cytokines. This was further validated when a concentration-dependent decrease in NO and ROS production was observed in zebrafish (Danio rerio) larvae. UaB also increased NRF2 activity in HaCaT/ARE cell line and attenuated NF-κB activation by inhibiting the nuclear translocation of transcription factor p65 in RAW 264.7 macrophages. Nontargeted LC-MS analysis of UaB revealed the presence of the flavonols quercitrin (1), quercetin (2), rutin (3), kaempferol (4), and kaempferol 3-O-rutinoside (5). Molecular docking indicates that major flavonol aglycones have high affinity toward COX-2 NSAID-binding sites, TNF-α, and TNF-α converting enzyme, while the glycosylated flavonoids showed strong binding toward iNOS and IKK-all possessing dynamic stability when performing molecular dynamics simulations at 140 ns. This is the first report to have elucidated the mechanistic anti-inflammatory potential of the Philippine endemic plant U. alba.

A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance and a spatial memory test. In our modified T-maze settings, electric shock punishment (1–2 V, 0.3–0.5 mA) is given at the left arm, with a green cue at the right arm. Also, the depth of both arms of the T-maze was increased. The parameters measured in our T-maze design were latency, freezing time, and time spent in different areas of the T-maze. We validated the utility of our modified T-maze protocol by showing the consistent finding of memory impairment in ZnCl₂−treated fish, which has been previously detected with the passive avoidance test. In addition, we also tested the spatial memory performance of leptin a (lepa) mutants which displayed an obesity phenotype. The results showed that although the learning and memory performance for lepa KO fish were similar to control fish, they displayed a higher freezing behavior during the training phase. In conclusion, we have established a modified T-maze protocol that can be used to evaluate the anxiety, learning, and memory capacity of adult zebrafish within three days, for the first time.

Bioavailability plays an important role in drug activity in the human body, as certain drug amounts should be present to elicit activity. However, low bioavailability of drugs leads to negligible use for human benefit. In this study, the diversely active neolignan, magnolol, was impregnated onto a Zr-based organometallic framework [Uio-66(Zr)] to increase its low bioavailability (4–5%) and to test its potential acute oral toxicity. Synthesis of Uio-66(Zr) was done through the solvothermal method while simple impregnation at different time points was used to incorporate magnolol. The loading capacity of Uio-66(Zr) at 36 h was found to be significantly higher at 72.16 ± 2.15% magnolol than in other incubation time. Based on the OECD 425 (limit test), toxicity was not observed at 2000 mg kg⁻¹ dose of mag@Uio-66(Zr) in female Sprague Dawley rats. The area under the curve (AUC) at 0–720 min of mag@Uio-66(Zr) was significantly higher than the AUC of free magnolol. Moreover, relative bioavailability increased almost two-folds using Uio-66(Zr). Unconjugated magnolol was found in the liver, kidney, and brain of rats in all treatment groups. Collectively, Uio-66(Zr) provided a higher magnolol bioavailability when used as drug carrier. Thus, utilization of Uio-66(Zr) as drug carrier is of importance for maximal use for poorly soluble and lowly bioavailable drugs.

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.