Oyagbemi, Ademola AdetokunboAdejumobi, Olumuyiwa AbiolaJarikre, Theophilus AghoghoAjani, Olumide SamuelAsenuga Ebunoluwa RachealGbadamosi, Idayat TitilayoAdedapo, Aduragbenro Deborah A.Aro, Abimbola O.Ogunpolu, Blessing SeunHassan, Fasilat OluwakemiFalayi, Olufunke OlubunmiOgunmiluyi, Iyanuoluwa OmololaOmobowale, Temidayo OlutayoArojojoye, Oluwatosin AdetolaOla-Davies, Olufunke EuniceSaba, Adebowale BenardAdedapo, Adeolu AlexEmikpe, Benjamin ObukowhoOyeyemi, Matthew OlugbengaNkadimeng, Sanah MalomileMcGaw, Lyndy JoyKayoka-Kabongo, Prudence NgalulaOguntibeju, Oluwafemi OmoniyiYakubu, Momoh Audu2023-10-312023-10-312022-03Oyagbemi, A.A., Adejumobi, O.A., Jarikre, T.A. et al. Clofibrate, a Peroxisome Proliferator–Activated Receptor-Alpha (PPARα) Agonist, and Its Molecular Mechanisms of Action against Sodium Fluoride–Induced Toxicity. Biological Trace Element Research 200, 1220–1236 (2022). https://doi.org/10.1007/s12011-021-02722-1.0163-4984 (print)1559-0720 (online)10.1007/s12011-021-02722-1http://hdl.handle.net/2263/93119AVAILABILITY OF DATA AND MATERIALS : Data will be made available based on request from the corresponding author.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.en© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021. The original publication is available at : https://link.springer.com/journal/12011.Sodium fluoride (NaF)Sodium fluoride toxicityAntihypertensiveApoptosisCell signallingOxidative stressHypertension (HTN)SDG-03: Good health and well-beingPostprint Article