Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

Abstract

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 518 BioFactors Research Communication 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

Ramipril blunts glycerol-induced acute renal failure in rats through its antiapoptosis, anti-inflammatory, antioxidant, and renin-inhibiting properties

“…Increase in AOPP contents is connected with oxidative stress, inflammation, and acute renal damage [46]. The inhibition of oxidative stress by ramipril in this study indicates that this drug not only inhibits angiotensin-converting enzyme, but it also inhibits the production of free radicals and ROS.…”

Honey and Its Phenolic Compounds as an Effective Natural Medicine for Cardiovascular Diseases in Humans?

“…It also prevented cardiac fibrosis and hypertrophy. Oyagbemi et al [81] indicate that the protective mechanism action of luteolin is also associated with the NF-κB/Nrf2 signaling pathways. They note that daily supplementation with 100 mg/kg and 200 mg/kg luteolin reduced high blood pressure and oxidative stress, including lipid peroxidation (expressed as MDA) and protein carbonylation, among 40 male Wistar albino rats.…”

Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health

“…Again, several human studies have found that exposure to excessive F is closely associated with hypertension [546,547,548,549,550]. Similar observations have been observed in experimental studies with rodents [551,552,553,554,555,556]. Interestingly, activation of the TRH system, with increased production of TRH and an upregulation of its receptors has also been implicated in the pathogenesis of hypertension [557].…”