Identify the Role of TLR 4 Mediated NF-KB Modulation in Cadmium Induced Neuroinflammation: Protection Potential of Quercetin

Abstract

Background: Cadmium, one of the toxic transition metals found in the earth's crust. High occupational exposure of cadmium distributes its presence in soil, air, and water. Mechanism suggests that disruption of the blood-brain barrier, increases oxidative stress, generation of reactive oxygen species, and proinflammatory markers that are responsible for neurodegeneration. Parkinson's pathology revealed that neuroinflammation plays a major role in dysfunction. The studies carried out that suggest potential role of cadmium in Parkinson’s pathology. Quercetin a flavonoid that shows antioxidant, anti-inflammatory, and neuroprotective properties. Elute to this the present study is designed to identify the role of TLR in cadmium induced neuroinflammation and the protective potential of quercetin. Objectives: To identify the role of TLR/IRAKs/NF-Kb in Cadmium-Induced Neuroinflammation in Parkinson’s Disease and establish the potential of quercetin in combating such modulations. Method: Adult male wistar rats acclimatization for seven days. Animals were divided into four groups: Normal control, Cadmium, Quercetin, and Cadmium + Quercetin. The rats received oral administration of the substance for 28 days. After that behavioral tests were assessed. Rats were sacrificed and tissue and samples were collected for biochemical analyses, including LPO, and catalase activity, alongside ELSA assays targeting TLR and NF-Kb. Results: The present study exhibits that cadmium exposure triggered neuroinflammation resulting in decreased locomotor activity, elevated oxidative stress, and increased expression of TLR4, IRAK4, TRAF 6, and NF – Kb. Quercetin intervention mitigation these effects, restoring locomotor activity, and oxidative stress and suppressing neuroinflammation by modulating the TLR4 pathway and acting as a neuroprotective role. Conclusion: The results of the present study indicated that cadmium-induced neuroinflammation is governed by Toll-Like Receptors mediated NF-kB signaling in Parkinson's disease and quercetin shows a protective role in cadmium-induced neuroinflammation.