Fluoride Intensifies Hypercaloric Diet-Induced ER Oxidative Stress and Alters Lipid Metabolism

Abstract

The role of fluoride (F) in oxidative stress is well reported, but its effects on the lipid metabolism has not been completely exploredBackgroundHere, we evaluated the relationship of diet and F-induced oxidative stress to lipid metabolism in the liver of rats eating normocaloric or hypercaloric diets for two time periods (20 or 60 days).MethodsSeventy-two 21-day-old Wistar rats were divided into 2 groups (n = 36) based on the type of diet they were eating; each of these groups was then further divided into another two groups (n = 18) based on the time periods of either 20 or 60 days, for a total of four groups. Each of these was divided into 3 subgroups (n = 6 animals/subgroup), dependent on the dose of F administered in the drinking water (0 mg/L(control), 15 mg/L or 50 mg/L). After the experimental period, blood samples and the liver were collected. Plasma samples were analyzed for HDL, cholesterol and triglycerides. Western blots were performed to probe for GRP78, Erp29, SOD2, Apo-E and SREBP in hepatic tissues.ResultsAs expected,the expression of target proteins involved in oxidative stress increased in the F-treated groups, especially in liver tissue obtained from animals eating a hypercaloric diet. Most changes in the lipid levels and pathological conditions were seen earlier in the time period, at day 20. The morphometric analyses showed a reduction in steatosis in groups on ahypercaloric diet and treated with 50 mg F/L compared to the control, while no changes were obtained in normocaloric-fed rats. Accordingly, plasma TG was reduced in the F-treated group. The reduced expression of Apo-E in a time- and diet-dependent pattern may account for the particular decrease in steatosis in hypercaloric-fed F-treated rats.ConclusionsThese results suggest that F changes liver lipid homeostasis, possibly because of the induction of oxidative stress, which seems to be higher in animals fed hypercaloric diets.

Moringa Oleifera Leaf Extract Repairs the Oxidative Misbalance following Sub-Chronic Exposure to Sodium Fluoride in Nile Tilapia Oreochromis niloticus

“…In different words, low concentration of fluoride (µM) might act as a promoter for cell proliferation and enzymatic activity; however, a high concentration of fluoride (mM) could act as an enzymatic inhibitor. This enzyme inhibitory action occurred due to the strong electronegativity of fluoride, where it forms ions and interacts with enzymes leading to toxicity and biological damage to different body systems [9], such as the central nervous system [10], spleen and immune organs [11], the male reproductive system [12], and the liver [13,14].…”

Hypercaloric Diet and Vitamin E Intake

“…The liver, the headquarter of important biochemical processes (gluconeogenesis, ureogenesis, oxidative phosphorylation, glycolysis, lipogenesis) is also an important player in the detoxification processes. The development of hepatic steatosis is influenced by a diet rich in saturated fat together with an increased lipogenesis process [20,21].…”

Proteomic analysis of mitochondria from rat liver exposed to chronic fluoride exposure in two experimental periods

“…Among these are cell cycle, ion transport, apoptosis, signaling pathways and metabolism of free radicals. These effects have been described in several organs and tissues such as liver, kidney, heart, brain, muscle and intestine (Whitford, 1996;Chlubek et al, 2003;Shanthakumari et al, 2004;Strunecka, 2007;Strunecka et al, 2007;Xiong et al, 2007;Blaszczyk et al, 2008;Chouhan e Flora, 2008;Kobayashi et al, 2009;Barbier et al, 2010;Inkielewicz-Stepniak e Czarnowski, 2010;Dey et al, 2011;Pereira et al, 2013;Lima Leite et al, 2014;Pereira et al, 2016;Melo et al, 2017;Dionizio, A. et al, 2018;Dionizio, A. S. et al, 2018;Malvezzi et al, 2018;Pereira et al, 2018).…”

“…The toxic effects of F have often been related as an important factor causing oxidative stress, defined as the sum of factors that cause an imbalance between the antioxidant enzymes and the reactive oxygen species (ROS) (Dabrowska et al, 2004;Suzuki et al, 2015;Zhou et al, 2015;Pereira et al, 2016). Mitochondria are considered the main sources of ROS and this has been related to the increase in the production of superoxide anions.…”