Adverse effects of polystyrene nanoplastic and its binary mixtures with nonylphenol on zebrafish nervous system: From oxidative stress to impaired neurotransmitter system.

Micro(nano)plastics generally co-exist with other chemicals in the environment, resulting in inevitable interaction and combined toxic effects on biota. Nevertheless, little is known regarding the interaction of nanoplastics (NPs) with other co-occurring insults. Hereby, we investigated single and combined effects of chronic exposure (45 days) to polystyrene nanoplastic particulates (PS-NPs) and nonylphenol (4-NP) on zebrafish nervous system. Multiple biomarkers concerning with oxidative-stress [catalase (CAT) activity and reduced glutathione (GSH) level], cholinergic system [Acetylcholinesterase (AchE) activity], glutamatergic system [glutamine synthetase (GS) and glutamate dehydrogenase (GDH) activities], energy metabolism [a-ketoglutarate dehydrogenase (a-KGDH) activity], and histological alterations were assessed. Both single and binary exposure to PS-NPs and 4-NP induced oxidative stress through reducing CAT activity and GSH level, in which a more sever effect was noticed in combined exposure. The AchE activity was significantly inhibited only in single treatment groups demonstrating antagonistic interaction between PS-NPs and 4-NP. Effects on GS activity was also alleviated in binary exposure as compared with single exposure to each contaminant. In addition, an increase in GDH activity was noticed in PS-NPs at 10 and 100 µg/L, and simultaneous presence of PS-NPs and 4-NP with a greater response were observed in combined treatments. PS-NPs and 4-NP either in separate or binary mixtures disrupted energy metabolism by deficiency of α-KGDH activity; however, co-exposure to PS-NPs and 4-NP induced more intense adverse impacts on this parameter. Furthermore, histological analysis revealed that 4-NP and PS-NPs, alone or in combination, reduced neural cells. These findings provide new insight into the neurotoxic effects of binary exposure to PS-NPs and 4-NP at environmentally relevant concentrations. Overall, our findings raise concerns about the presence and toxicity of nano-scale plastic particulates and highlight the importance of investigating the interaction of Micro(nano)plastics with other environmental irritants.

Phosphonate analog of 2-oxoglutarate regulates glutamate-glutamine homeostasis and counteracts amyloid beta induced learning and memory deficits in rats.

BACKGROUND: Metabolic alteration is a mainstream concept underlying the cognitive decline in neurodegenerative disorders including Alzheimer's disease (AD). Mitochondrial enzyme α-ketoglutarate dehydrogenase complex (α-KGDHC) seems to play a dual-edged sword role in cytotoxic insult. Here, using succinyl phosphonate (SP), a specific α-KGDHC inhibitor, we aimed to examine its potential action on AD progression. METHODS: Male Wistar rats were assigned to two separate experiments. First, they were bilaterally microinjected into the dorsal CA1 area by amyloid-beta (Aß)25-35 for four consecutive days. Seven days after the last injection, they were trained to acquire Morris Water Maze (MWM) task for three successive days when they were treated with SP after each training session. In the second experiment, SP was administered 30 min after the first Aß microinjection and behavioral tests were performed one week after the last Aß administration. The activity of glutamate dehydrogenase (GDH), and glutamine synthetase (GS), as key enzymes involved in glutamate-glutamine homeostasis and histological assays were evaluated in the hippocampi. RESULTS: Our behavioral results indicated that post-training SP treatment enhanced task acquisition but did not change memory performance in Aß-treated rats. However, administration of SP at the time of Aß injection precludes the deteriorative effect of Aß and neuronal injury on both spatial learning and memory performances indicating its preventive action against Aß pathology at its early stages. Measurement of enzymes activity shows that α-KGDHC activity was reduced in the Aß treated group, and SP administration restored its activity; also, GDH and GS activities were increased and decreased respectively due to Aß, and SP reversed the action of Aß on these enzymes. CONCLUSIONS: This study proposes that SP possibly a promising therapeutic approach to improve memory impairment in AD, especially in the early phases of this disease.

Folic acid conjugated bovine serum albumin: An efficient smart and tumor targeted biomacromolecule for inhibition folate receptor positive cancer cells.

This work described a folic acid conjugated delivery of chrysin-loaded bovine serum albumin nanoparticles, which could overcome the nonspecific targeting disadvantage. Chrysin (5, 7-dihydroxyflavone) is a natural flavonoid which have some significant biological effects on the processes of chemical defense. Chrysin loaded bovine serum albumin nanoparticles (Chrysin-BSA NPs) were synthesized by a simple desolvation procedure. Afterward, folic acid (FA) was conjugated to the surface of Chrysin-BSA NPs by carbodiimide chemistry (Chrysin-BSA-FA NPs). The resultant Chrysin-BSA-FA NPs showed a spherical shape, with a hydrodynamic diameter of 97.5 ±â€¯5.8 nm (mean ±â€¯SD) nm and a ζ-potential of -11.3 mV. The in vitro drug release study of chrysin presented a sustained and controlled release pattern. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. Both the Chrysin-BSA NPs and Chrysin-BSA-FA NPs prompted an enhanced cancer cell cytotoxic effect in contrast to chrysin solution. These data recommended that the folate-modified chrysin -loaded vehicle, which demonstrated better biocompatibility and potential superiority, could be a suitable cancer therapy in targeting tumors in the future.

Production of biological nanoparticles from bovine serum albumin as controlled release carrier for curcumin delivery.

This study described a curcumin (CUR) loaded bovine serum albumin nanoparticles (BSA@CUR NPs), which could solubilize the poorly water-soluble drug and increase the therapeutic efficacy of the drug. BSA@CUR NPs were synthesized by a simple coacervation procedure. The resultant BSA@CUR NPs showed a spherical shape, with a diameter of 92.59±16.75nm (mean ± SD) nm and a ζ-potential of - 9.19mV. The in vitro drug release study of CUR showed a sustained and controlled release pattern. Cellular toxicity of BSA NPs was also investigated on HFF2 cell lines. Additionally, a hemolysis test of as prepared NPs were performed for investigation of hemocompatibility. Hemolysis assay and cytotoxicity study results on HFF-2 cell line show that as prepared BSA NPs are biocompatible. The in vitro anticancer activity of the BSA@CUR NPs were performed by MTT assay on MCF-7 cancer cells. These results suggest that BSA@CUR NPs are a new drug delivery system for cancer therapy.