Restorative effect of l-Dopa treatment against Ochratoxin A induced neurotoxicity


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Abstract

The toxic effects of Ochratoxin A (OTA), a fungal secondary metabolite of the genera Aspergillus and Penicillium with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) a Parkinson inducing drug were investigated to evaluate the neurotoxic effects exerted by OTA. OTA is known to contaminate food and feedstuff leading to a wide range of toxicity like nephrotoxicity, hepatotoxicity, and immunotoxicity. However, due to the dearth of available information on the possible mechanisms of OTA neurotoxicity and neurodegeneration the current study was undertaken. Hence, in this study, we examined the neurotoxic effects and the possible mechanism of action of neurodegeneration by OTA toxicity on mice brain by conducting a battery of behavioural studies and reviewing neurotransmitter levels and neuronal apoptotic pathways. Further, they were treated with l-Dopa, a precursor of dopamine (DA) to explore its ameliorative effects against OTA. The results of behavioural studies like gait analysis, spontaneous activity, cylinder test and pole test showed that OTA exhibits Parkinsonian physiognomies which were stabilized with l-Dopa treatment. Also, OTA toxicity showed insults on neurotransmitter levels and general brain function parameters that were normalized with l-Dopa treatment. The results of the present study suggest that OTA promotes neurodegeneration by targeting neuronal pathway leading to the development of Parkinson's diseases.HighlightsOTA induced neurotoxic effects and Parkinsonian physiognomies in a battery of behavioral studies.OTA activates FoxO3 initiating apoptosis in Akt neuronal pathway by inhibiting PI3k/Akt pathway.Ameliorative effects of l-Dopa against OTA and MPTP neurodegeneration was studied by monitoring the change in Neurotransmitter levels, brain function, brain protein levels, ROS generation, total antioxidant status and lipid peroxidation.

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