Neurotoxic effects induced by flunitrazepam and its metabolites in zebrafish: Oxidative stress, apoptosis, and histone hypoacetylation.

Sci Total Environ

School of Environment and Energy, South China University of Technology, Guangzhou 510006, PR China; The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006, PR China; The Key Laboratory of Environmental Protection and Eco-Remediation of Guangdong Regular Higher Education Institutions, Guangzhou 510006, PR China. Electronic address:

Published: March 2024

Benzodiazepines (BZDs) have been widely detected in aquatic environments, but their neurotoxic effects and potential mechanisms are still unclear. This study focuses on flunitrazepam (FLZ) and its metabolite, 7-aminoflunitrazepam (7-FLZ), as representative psychotropic BZD. We investigated their neurotoxic effects on adult zebrafish following a 30-day exposure to environmentally relevant concentrations. The findings reveal that exposure to these drugs induces anxiety-like and aggressive behaviors in zebrafish. Additionally, notable morphological damage to brain tissue and mitochondrial structures was observed. Through TUNEL staining, an increase in apoptotic cells was detected in the brain tissue of the exposed group, accompanied by marked elevations in ROS and caspase-3/9 levels. The upregulation of apoptosis-related genes Bax, p53, and Bcl-2 confirmed the occurrence of apoptosis. Furthermore, exposure to the drugs resulted in decreased acetylation levels of brain histones H3 and H4. The upregulation of histone deacetylation enzyme genes (HDAC1, HDAC3, HDAC4, and HDAC6) supported this result. Molecular docking results suggest that compared to 7-FLZ, FLZ has a higher binding affinity with HDAC3 and HDAC4, explaining why it causes lower histone acetylation levels. This study in zebrafish elucidates the neurotoxicity and molecular mechanisms induced by FLZ and 7-FLZ, which is significant for further understanding the impact of BZDs on human health and assessing their ecological risks.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2024.170521DOI Listing

Publication Analysis

Top Keywords

neurotoxic effects
12
exposure drugs
8
brain tissue
8
acetylation levels
8
hdac3 hdac4
8
effects induced
4
induced flunitrazepam
4
flunitrazepam metabolites
4
zebrafish
4
metabolites zebrafish
4

Similar Publications

Background: We investigated chitosan's protective effects against tertiary butylhydroquinone (TBHQ)-induced toxicity in adult male rats, focusing on cognitive functions and oxidative stress in the brain, liver, and kidneys.

Methods: Rats were divided into four groups (n = 8/group): (1) Control, (2) Chitosan only, (3) TBHQ only, and (4) Chitosan + TBHQ.

Results: TBHQ exposure led to significant cognitive impairments and increased oxidative stress, marked by elevated malondialdehyde (MDA) and decreased superoxide dismutase (SOD) and glutathione (GSH) levels.

View Article and Find Full Text PDF

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked to disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) is metabolized via the Trp-kynurenine (KYN) metabolic pathway, which generates a variety of bioactive molecules. Dysregulation of KYN metabolism, particularly low levels of kynurenic acid (KYNA), appears to be linked to neuropsychiatric disorders.

View Article and Find Full Text PDF

Background/objectives: Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease and contributing to neurotoxicity and neuroinflammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with combined antiretroviral therapy (cART), HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin.

View Article and Find Full Text PDF

Fourier Transform Infrared Spectroscopy Analysis as a Tool to Address Aβ Impact on Extracellular Vesicles.

Molecules

January 2025

Neuroscience and Signalling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal.

Alzheimer's disease is a challenge in modern healthcare due to its complex etiology and increasing prevalence. Despite advances, further understanding of Alzheimer's disease pathophysiology is needed, particularly the role of Aβ neurotoxic peptide. Fourier transform infrared spectroscopy (FTIR) has shown potential as a screening tool for several pathologies, including Alzheimer's disease.

View Article and Find Full Text PDF

Botulinum toxin (BoNT), the most potent substance known to humans, likely evolved not to kill but to serve other biological purposes. While its use in cosmetic applications is well known, its medical utility has become increasingly significant due to the intricacies of its structure and function. The toxin's structural complexity enables it to target specific cellular processes with remarkable precision, making it an invaluable tool in both basic and applied biomedical research.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!