Mitigating Heavy Metal- and Organophosphate-Induced Neurotoxicity: The Therapeutic Role of Plant Polyphenols

Heavy metals and organophosphate pesticides are pervasive environmental neurotoxicants that converge on oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter dysregulation, and neuronal apoptosis. Given the limited capacity of current therapeutic approaches to mitigate persistent neural injury, plant-derived polyphenols have emerged as promising multitarget neuroprotective candidates. This narrative review critically synthesizes preclinical evidence on the neuroprotective activity of plant polyphenols against heavy metal- and organophosphate-induced neurotoxicity. A systematic search of PubMed, Scopus, Web of Science, and Google Scholar identified representative experimental studies encompassing flavonoids and non-flavonoid polyphenols, including quercetin, rutin, resveratrol, curcumin, naringenin, epigallocatechin gallate, fisetin, myricetin, and ellagic acid. Across experimental models, polyphenols consistently attenuated oxidative injury, restored endogenous antioxidant defenses, and modulated key signaling networks, particularly Nrf/HO-) and NF-κB. Their protective effects additionally encompassed preservation of mitochondrial integrity, normalization of neurotransmission, attenuation of neuroinflammation, and inhibition of apoptotic signaling, with several compounds improving cognitive, behavioral, and synaptic outcomes. Collectively, the evidence supports a convergent multitarget mechanism whereby polyphenols act on shared downstream pathological nodes rather than the initiating toxicant-specific targets. However, substantial interstudy heterogeneity, limited bioavailability and central nervous system delivery, variable treatment paradigms, and the predominance of animal and cellular models constrain clinical translation. Further studies addressing pharmacokinetics, brain bioavailability, environmentally relevant chronic exposures, and standardized dosing are warranted to determine the translational potential of polyphenols as preventive or adjunctive interventions for environmentally induced neurotoxicity.

کلیدواژه ها:

Plant polyphenols ، Heavy metals ، Organophosphate pesticides ، Neurotoxicity ، Neuroprotection ، Neuroinflammation ، Mitochondrial dysfunction ، Environmental toxicants