1. Clofibrate, a Peroxisome Proliferator–Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride–Induced Toxicity
- Author
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Ademola Adetokunbo Oyagbemi, Ebunoluwa Racheal Asenuga, Benjamin Obukowho Emikpe, Olufunke Eunice Ola-Davies, O S Ajani, Oluwatosin Adetola Arojojoye, Aduragbenro D.A. Adedapo, Theophilus Aghogho Jarikre, A.O. Aro, Fasilat Oluwakemi Hassan, Lyndy Joy McGaw, Idayat Titilayo Gbadamosi, Temidayo Olutayo Omobowale, Iyanuoluwa Omolola Ogunmiluyi, Adebowale Benard Saba, Matthew Olugbenga Oyeyemi, Oluwafemi Omoniyi Oguntibeju, Momoh A. Yakubu, Olumuyiwa Abiola Adejumobi, Olufunke Olubunmi Falayi, Adeolu Alex Adedapo, Sanah M. Nkadimeng, Prudence Ngalula Kayoka-Kabongo, and Blessing Seun Ogunpolu
- Subjects
Agonist ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,010501 environmental sciences ,Pharmacology ,01 natural sciences ,Biochemistry ,Nephrotoxicity ,Nitric oxide ,Inorganic Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Sodium fluoride ,medicine ,0105 earth and related environmental sciences ,0303 health sciences ,Clofibrate ,030302 biochemistry & molecular biology ,Biochemistry (medical) ,General Medicine ,chemistry ,Toxicity ,Peroxisome proliferator-activated receptor alpha ,Fluoride ,medicine.drug - Abstract
Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride.
- Published
- 2021
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