1. Clofibrate, a PPAR‐α agonist, abrogates sodium fluoride‐induced neuroinflammation, oxidative stress, and motor incoordination via modulation of GFAP/Iba‐1/anti‐calbindin signaling pathways
- Author
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Fasilat Oluwakemi Hassan, James O. Olopade, Olufunke Olubunmi Falayi, Oluwabusayo R Folarin, Lyndy Joy McGaw, Temidayo Olutayo Omobowale, Kabirat Adigun, Momoh A. Yakubu, Olumuyiwa Abiola Adejumobi, Olamide E. Adebiyi, Ebunoluwa Rachael Asenuga, Adeolu Alex Adedapo, Ademola Adetokunbo Oyagbemi, Blessing Seun Ogunpolu, Adedeji K Adebayo, Sanah M. Nkadimeng, Oluwafemi Omoniyi Oguntibeju, Olufunke Eunice Ola-Davies, and Adebowale Bernard Saba
- Subjects
Male ,Agonist ,Calbindins ,medicine.drug_class ,Health, Toxicology and Mutagenesis ,010501 environmental sciences ,Management, Monitoring, Policy and Law ,Pharmacology ,Toxicology ,medicine.disease_cause ,01 natural sciences ,Neuroprotection ,Fluorides ,Random Allocation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glial Fibrillary Acidic Protein ,Sodium fluoride ,medicine ,Animals ,PPAR alpha ,Clofibrate ,Rats, Wistar ,Neuroinflammation ,0105 earth and related environmental sciences ,Inflammation ,Glial fibrillary acidic protein ,biology ,Chemistry ,Calcium-Binding Proteins ,Microfilament Proteins ,General Medicine ,Rats ,Oxidative Stress ,Neuroprotective Agents ,030220 oncology & carcinogenesis ,Toxicity ,biology.protein ,Sodium Fluoride ,Ataxia ,Biomarkers ,Oxidative stress ,Signal Transduction ,medicine.drug - Abstract
Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders.
- Published
- 2019
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