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<p>Lead (Pb) neurotoxicity is characterized by persistent cognitive and motor impairments that arise from converging disturbances in mitochondrial function, oxidative balance, and neuroinflammatory signaling. Increasing evidence suggests that these pathological outcomes are closely linked to disruption of Transcription Factor EB (TFEB), a key regulator of autophagy-lysosomal pathways and mitochondrial quality control. Impaired TFEB function can promote the accumulation of dysfunctional mitochondria and perpetuate oxidative and inflammatory cascades, thereby exacerbating Pb-induced neurodegeneration. The present study evaluated whether caffeic acid (CFA) protects against Pb-induced neurotoxicity and investigated the involvement of TFEB signaling in its neuroprotective effects. Wistar rats were exposed to lead acetate (100&#xa0;mg/kg, p.o.) for 30 days, followed by treatment with caffeic acid (CFA; 20 and 40&#xa0;mg/kg). To validate the mechanistic role of TFEB, eltrombopag, a TFEB inhibitor, was co-administered in dedicated groups. Behavioral outcomes were assessed using the Morris Water Maze and rota rod tests, and hippocampal and cerebellar tissues were examined for mitochondrial complex I–III activities, oxidative stress indices (TBARS, GSH), and inflammatory mediators (TNF-α, IL-1β, NF-κB). Pb exposure produced marked spatial memory deficits, motor impairment, suppression of mitochondrial complex activities, oxidative imbalance, and enhanced inflammatory signaling. CFA treatment attenuated these alterations; however, these benefits were lost upon TFEB inhibition. Collectively, these findings demonstrate that CFA attenuates Pb-induced behavioral and biochemical alterations and suggest that its neuroprotective effects are mediated, at least in part, through TFEB-associated pathways.</p>

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Caffeic Acid Mitigates Behavioral and Biochemical Alterations in Lead-induced Neurotoxicity in Rats With Possible Involvement of TFEB

  • 期刊论文

  • 发表日期：

    2026年7月20日

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  • Pratham Gautam,
  • Varinder Singh,
  • Navjot Kanwar,
  • Tanveer Singh,
  • Manjinder Singh,
  • Thakur Gurjeet Singh,
  • Amarjot Kaur Grewal,
  • Ravinder Singh,
  • Sheikh F. Ahmad,
  • Haneen A. Al-Mazroua

摘要

Lead (Pb) neurotoxicity is characterized by persistent cognitive and motor impairments that arise from converging disturbances in mitochondrial function, oxidative balance, and neuroinflammatory signaling. Increasing evidence suggests that these pathological outcomes are closely linked to disruption of Transcription Factor EB (TFEB), a key regulator of autophagy-lysosomal pathways and mitochondrial quality control. Impaired TFEB function can promote the accumulation of dysfunctional mitochondria and perpetuate oxidative and inflammatory cascades, thereby exacerbating Pb-induced neurodegeneration. The present study evaluated whether caffeic acid (CFA) protects against Pb-induced neurotoxicity and investigated the involvement of TFEB signaling in its neuroprotective effects. Wistar rats were exposed to lead acetate (100 mg/kg, p.o.) for 30 days, followed by treatment with caffeic acid (CFA; 20 and 40 mg/kg). To validate the mechanistic role of TFEB, eltrombopag, a TFEB inhibitor, was co-administered in dedicated groups. Behavioral outcomes were assessed using the Morris Water Maze and rota rod tests, and hippocampal and cerebellar tissues were examined for mitochondrial complex I–III activities, oxidative stress indices (TBARS, GSH), and inflammatory mediators (TNF-α, IL-1β, NF-κB). Pb exposure produced marked spatial memory deficits, motor impairment, suppression of mitochondrial complex activities, oxidative imbalance, and enhanced inflammatory signaling. CFA treatment attenuated these alterations; however, these benefits were lost upon TFEB inhibition. Collectively, these findings demonstrate that CFA attenuates Pb-induced behavioral and biochemical alterations and suggest that its neuroprotective effects are mediated, at least in part, through TFEB-associated pathways.