Ecotoxicity Assessment of Fe3O4 Magnetic Nanoparticle Exposure in Adult Zebrafish at an Environmental Pertinent Concentration by Behavioral and Biochemical Testing

Abstract

Magnetic Nanoparticles (MNPs) are widely being investigated as novel promising multifunctional agents, specifically in the fields of development for theranostics, electronics, waste water treatment, cosmetics, and energy storage devices. Unique, superior, and indispensable properties of magnetization, heat transfer, and melting temperature make MNPs emerge in the field of therapeutics in future healthcare industries. However, MNPs ecotoxicity as well as behavioral toxicity is still unexplored. Ecotoxicity analysis may assist investigate MNPs uptake mechanism and its influence on bioavailability under a given set of environmental factors, which can be followed to investigate the biomagnification of MNPs in the environment and health risk possessed by them in an ecological food chain. In this study, we attempted to determine the behavioral changes in zebrafishes at low (1 ppm) or high (10 ppm) concentration levels of Fe3O4 MNPs. The synthesized Fe3O4 MNPs sized at 15 nm were characterized by the transmission electron microscope (TEM), the superconducting quantum interference device (SQUID) magnetometer, and the multiple behavior tests for novel tank, mirror biting, conspecific social interaction, shoaling, circadian rhythm, and short-term memory of zebrafish under MNPs chronic exposure were demonstrated. Low concentration MNP exposure did not trigger alteration for majority behavioral and biochemical tests in adult zebrafish. However, tight shoal groups were observed at a high concentration of MNPs exposure along with a modest reduction in fish exploratory behavior and a significant reduction in conspecific social interaction behavior. By using enzyme-linked immunosorbent assays (ELISA), we found a high dose of MNPs exposure significantly elevated cortisol, acetylcholine, and catalase levels while reducing serotonin, acetylcholine esterase, and dopamine levels in the brain. Our data demonstrates chronic MNPs exposure at an environmentally-relevant dose is relatively safe by supporting evidence from an array of behavioral and biochemical tests. This combinational approach using behavioral and biochemical tests would be helpful for understanding the MNPs association with anticipated colloids and particles effecting bioavailability and uptake into cells and organisms.

Potential Toxicity of Iron Oxide Magnetic Nanoparticles: A Review

“…Similarly, for in vitro cytotoxicity analysis when a lactate dehydrogenase (LDH) assay was performed in a BeWo b30 placental barrier model, all concentrations of uncoated Fe 3 O 4 released LDH except 3 µg/cm 2 after 24 h exposure and LDH levels were elevated from cells treated with uncoated Fe 3 O 4 at 75 and 15 ug/cm 2 representing a significant time-dependent increase of toxicity at high concentrations of 15 and 75 µg/cm 2 for uncoated Fe 3 O 4 , but not for OC-Fe 3 O 4 MNPs [ 82 ]. In a zebrafish system, Malhotra and colleagues also found that carbon-coated Fe 3 O 4 MNPs displayed superior biosafety compared to uncoated ones based on neurobehavioral and biochemical assays [ 80 ]. All these phenomena indicate that a lot of factors are involved in understanding the toxicity on a cellular and organism basis depending on dosage, concentration, time, surface chemistry, cell type, interaction medium, internalization mode, which need very elaborate studies to understand the fundamental mechanism properly in accordance to be able to use the MNPs in healthcare.…”

“…In a recent study, Malhotra and colleagues discovered that bare Fe 3 O 4 MNPs (15 nm) exposure can trigger behavioral and biochemical alterations in zebrafish. They incubated adult zebrafish with either low dose (1 ppm) or high dose (10 ppm) bare Fe 3 O 4 MNPs for 14 days and discovered no significant abnormalities at behavioral and biochemical levels in the low concentration group, whereas, significant changes in aggressiveness, speed, and locomotion behavior coupled with substantial changes in neurotransmitters and stress hormones were induced in the brains when zebrafish were challenged with high dose of Fe 3 O 4 MNPs [ 80 ]. Next, Malhotra and colleagues further tested the idea whether the toxicity of bare Fe 3 O 4 MNPs can be reduced if their surface was coated with inert substances like carbon.…”

Circadian rhythms in zebrafish (Danio rerio) behaviour and the sources of their variability

“…Recent interest has focussed on using the circadian rhythm of zebrafish locomotor activity as a metric for toxicity assessment (Li et al, 2017;Pan et al, 2017;Yang et al, 2018;Sarasamma et al, 2018aSarasamma et al, ,b, 2019Audira et al, 2019;Malhotra et al, 2019;Aluru et al, 2020;Zhao et al, 2020). The available data are summarized in Table 2.…”

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation

“…The potential of toxicity of iron oxide NPs greatly depends on the different combinations and functionalization used. In vivo and in vitro studies on the safety of uncoated iron oxide NPs displayed cytotoxicity in erythrocytes [713] and neurobehavioral toxicity at 10 ppm [714]. However, another study did not indicate any inherent toxicity for uncoated iron oxide NPs [702].…”