Luteolin-mediated Kim-1/NF-kB/Nrf2 Signaling Pathways Protects Sodium Fluoride-induced Hypertension and Cardiovascular Complications

The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life. However, flavonoids such as Luteolin might be of great value in the prevention of toxicity associated with accidental or inevitable ingestion of NaF. In the study, 40 male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group and received normal saline, Group B was exposed to NaF at 300 ppm (300 mg/L) in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and coadministered with Luteolin orally daily at a dosage of 100 mg/kg and 200 mg/kg for the same time point. Our results indicated that NaF caused significant increases in systolic blood pressure, diastolic blood pressure, mean arterial pressure, malondialdehyde, protein carbonyl, myeloperoxidase, advanced oxidative protein products, together with significant reductions in glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and nitric oxide (NO) bioavailability. The electrocardiogram results showed that NaF alone caused significant prolongation of QT and QTc intervals. Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI). Together, Luteolin coadministration with NaF improved NO bioavailability, reduced high blood pressure, markers of oxidative stress, reversed prolongation of QT and QTc intervals, and lowered the expressions of Kim-1, NF-κB, and CTnI. © 2018 BioFactors, 44(6):518-531, 2018.