Suppression of Mitochondrial Oxidative Phosphorylation and TCA Enzymes in Discrete Brain Regions of Mice Exposed to High Fluoride: Amelioration by Panax ginseng (Ginseng) and Lagerstroemia speciosa (Banaba) Extracts

Abstract

Chronic fluoride intoxication results in pathophysiological complications pertaining to soft tissues, called non-skeletal fluorosis. This study examined whether fluoride-induced alterations in selected parameters that are indicative of mitochondrial dysfunction accompany the toxic effects of fluoride in discrete brain regions in vivo and also explored the possibility of treatment with Ginseng (GE) and Banaba (BLE) either alone or with their co-exposure which is capable of reversing parameters indicative of fluoride-induced impairments in mitochondrial function. Swiss mice, Mus musculus, were given 270 ppm fluoride (600 ppm NaF) in their drinking water for 30 days, while continuing the fluoride exposure, toxicated animals were given differential doses (50-250 mg/kg body wt) of phytoextracts through oral gavage for 2 weeks. Discrete brain regions separated from dissected animals to perform biochemical assessments. Disturbances in mitochondrial enzyme complexes (I-IV) and decrements in TCA enzymes (ICDH, SDH, and aconitase) were noted in discrete brain regions upon F exposure, suggesting mitochondrial dysfunction. In addition, a significant reduction in oxidative stress indices with increased MDA content as well as decrease in reduced glutathione content and increases in catalase and SOD enzyme activity suggests the involvement of severe oxidative stress affecting the mitochondrial function(s). Treatment with either GE or BLE reversed F-induced alterations in augmenting the suppressed complex enzymes followed by TCA enzymes and oxidative stress indices in a dose independent manner. However, the co-exposure of GE and BLE at a dose of 150 mg/kgbw appeared to restore mitochondrial functioning. These results provide in vivo evidence supporting the hypothesis that fluoride induces impairments in mitochondrial function, which can be reversed by treatment with GE and BLE as well their co-exposure at 150 mg/kgbw.

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

“…Due to their limited glycolytic capabilities, these cells depend on the processes of oxidative phosphorylation which is the main source of energy in the central nervous system. The energy created by mitochondria is used for the activity of membrane ion channels and for the transmission of impulses through synapses, and the dysfunction of these organelles is observed in neurodegenerative illnesses [27, 28]. One of the important factors influencing the energy metabolism of neurons is the transportation, absorption and transformation of glucose, because it serves as the main source of energy for neurons [29].…”

“…Another study carried out on mice confirmed that fluorine influences the activity of complexes of the respiratory chain and of enzymes of the citric acid cycle. A decrease in the activity of complexes I, II, III and IV; isocitrate dehydrogenase and succinate dehydrogenase was observed in the cerebral cortex, cerebellum and hippocampus of mice exposed to high concentrations of fluorine (the concentration of fluorine in drinking water, 270 mg/L) [27]. …”

“…A decrease in the activity of the respiratory chain complexes influences the increase in the synthesis of ROS which activate the pathways leading to the degradation of mitochondria as well as the entire cell [27]. ROS and the products of lipid peroxidation are also responsible for the formation of compounds that block the active area of isocitrate dehydrogenase, consequently inhibiting the oxidative decarboxylation of the isocitrate in the Krebs cycle and influencing the activity of this pathway.…”

Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway

“…The fluoride levels in the plasma and kidney were estimated measured according to a potentiometric method 1 using Thermo Orion 720A+ with fluoride ion sensitive electrode 9609BNWP (Thermo, USA).…”

“…The literature pertaining to the occurrence of environment fluoride (F) and its relationship to human health by researchers is in large quantities and spans a wide variety of disciplines for over 100 years 1 . Although in low dose, it can help strengthen bones and prevent dental caries, however, for instance, due to the wide usage of F in industrial processes, accumulating evidence showed that excessive F exposure causes a variety of adverse effects on soft tissues 2 .…”