Mechanisms of Neurotoxicity of Organophosphate Pesticides and Their Relation to Neurological Disorders

Neuropsychiatric Disease and Treatment, Journal Year: 2024, Volume and Issue: Volume 20, P. 2237 - 2254

Published: Nov. 1, 2024

Organophosphates (OPs) refers to a diverse group of phosphorus-containing organic compounds; they are widely used all over the world and have had an important beneficial impact on industrial agricultural production control vector transmission. Exposure OPs different toxicities (high, moderate, slight, low toxicity) can negative consequences nervous system, such as nausea, vomiting, muscle tremors, convulsions. In severe cases, it lead respiratory failure or even death. Notably, induce neuropathy in system through specific interactions with nicotinic muscarinic receptors, phosphorylating acetylcholinesterase, neuropathic target esterases. This review summarizes possible toxicological mechanisms their interplay underlying OP pesticide poisoning, including cholinesterase inhibition non-cholinesterase mechanisms. It outlines links between poisoning neurological disorders, dementia, neurodevelopmental diseases, Parkinson's disease. Additionally, explores interactions' potential therapeutic implications that may help mitigate deleterious system.

Language: Английский

Different Mechanisms in Doxorubicin-Induced Neurotoxicity: Impact of BRCA Mutations

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4736 - 4736

Published: May 15, 2025

The genotoxic drug doxorubicin (Dox) remains one of the most powerful chemotherapeutic options available for a wide range cancers including breast, ovarian, and other cancers. However, emerging evidence links Dox treatment with chemotherapy-induced cognitive impairment, condition that is popularly referred to as Dox-induced neurotoxicity or “chemobrain”, which limits use drug. There are no specific treatments neurotoxicity, only interventions mitigate neurotoxic effects Accumulating indicates DNA damage, oxidative stress, dysregulation autophagy neurogenesis, inflammation, apoptosis play central roles in neurotoxicity. Additionally, germline mutations tumour suppressor genes breast cancer susceptibility 1 2 (BRCA1 BRCA2) increase risk related BRCA1 BRCA2 distinct proteins crucial, unique homologous recombination-mediated double-stranded break repair. Furthermore, stress both neural cells brain microvascular endothelial cells, suggests they have critical role regulators pathways development Despite research on function, there gap knowledge about In this review, we discuss existing findings different mechanisms along future perspectives.

Language: Английский

Diethyl nitrosamine-induces neurobehavioral deficit, oxido-nitrosative stress in rats' brain: a neuroprotective role of diphenyl diselenide

BMC Neuroscience, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 25, 2024

Diethylnitrosamine (DEN), a common dietary carcinogen, is associated with neurotoxicity in humans and animals. This study investigated the neuroprotective effects of diphenyl diselenide (DPDS) against DEN-induced male Albino Wistar rats (n = 40). Rats were randomly distributed into cohorts treated as follows: vehicle control (corn oil 2 mL/kg; gavage), DPDS-only (5 mg/kg; gavage) DEN-only (200 single dose i.p.). Also, two other rat pre-treated DPDS (3 or 5 mg/kg) for 15 days (day: 0–15), subsequently administered DEN continuously another 7 days, (days:15–21). Behavioural tests (OFT- using open field test; NORT- novel object recognition FST- forced swimming test Y-maze) conducted from 19–21, followed by biochemical analysis hippocampus prefrontal cortex oxidative stress, inflammation, neurotransmitter metabolic enzyme, histopathology. DEN-treated exhibited decreased locomotor activity, spatial memory function antioxidant increased nitration anxiety, depressive-like behaviour, causing histoarchitectural damage hippocampal cortices. treatment (pre- post-DEN exposure) significantly alleviated these neurotoxic, oxidative, effects, reversed histopathological alterations, improved locomotive cognitive functions. In conclusion, demonstrates potent toxicity, likely through enhanced endogenous capacity that mitigates oxido-nitrative damage. These findings suggest organo-selenium -DPDS- promising chemotherapeutic agent alleviating DEN-mediated maintaining brain health.

Language: Английский