Oyagbemi, Ademola AdetokunboAjibade, Temitayo OlabisiEsan, Oluwaseun OlanrewajuAdetona, Moses OlusolaAwoyomi, Omolola VictoriaOmobowale, Temidayo OlutayoOla-Davies, Olufunke EuniceSaba, Adebowale BenardAdedapo, Adeolu AlexNkadimeng, Sanah MalomileMcGaw, Lyndy JoyKayoka-Kabongo, Prudence NgalulaYakubu, Momoh AuduNwulia, EvaristusOguntibeju, Oluwafemi Omoniyi2025-05-302025-05-302024-02Oyagbemi, A.A., Ajibade, T.O., Esan, O.O. et al. Cardioprotective and renoprotective effects of melatonin and vitamin E on fluoride-induced hypertension and renal dysfunction in rats. Comparative Clinical Pathology 33, 33–45 (2024). https://doi.org/10.1007/s00580-023-03519-5.1618-5641 (print)1618-565X (online)10.1007/s00580-023-03519-5http://hdl.handle.net/2263/102587DATA AVAILABILITY : Data will be made available on request.Fluoride is an important toxicological and environmental toxicant that is implicated in diverse cardiorenal system dysfunctions via the induction of oxidative stress. The present study aims at evaluating the cardioprotective and renoprotective effects of melatonin and vitamin E on fluoride toxicity on biomarkers of oxidative stress, clinical pathology, and their molecular mechanism of action. Apparently healthy male rats of the Wistar strain (n = 50; 160 ± 7.5 g), were randomly distributed into five groups of ten animals per group as follows: Control, sodium fluoride (NaF, 25 mg/kg), NaF and melatonin 20 mg/kg i.p.; NaF and vitamin E 50 mg/kg p/o, NaF plus melatonin and vitamin E administered orally. NaF and melatonin were administered for fifteen consecutive days, whereas vitamin E was administered every 72 h. Blood pressure parameters, oxidative stress biomarkers, electrocardiography, histopathology, and immunohistochemical staining were performed. From this study, NaF intoxication provoked reduction in renal and cardiac systemic antioxidants, alterations of haemodynamic and electrocardiographic parameters, heightened blood urea nitrogen (BUN), creatinine, angiotensin converting enzyme, angiotensin 2 type 1 receptor, kidney injury molecule 1, interleukin 1 beta in the renal tissues, cardiac troponin, and nuclear kappa beta. However, the administration of either melatonin or vitamin E, and its combination mitigated high blood pressure, normalized electrocardiographic changes, abrogated biomarkers of oxidative stress, improved renal function, and attenuated inflammation. The combination of melatonin and vitamin E effectively mitigated cardiovascular and renal toxicities associated with fluoride intoxication through the prevention of cardio-renal dysfunction, oxidative stress, and inflammatory processes.en© The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature 2023. The original publication is available at http://link.springer.comjournal/580.FluorideHypertensionMelatoninRatsVitamin EPostprint Article