Increase of complex I and reduction of complex II mitochondrial activity are possible adaptive effects provoked by fluoride exposure

Abstract

Fluoride (F) can induce changes in the expression of several liver proteins, most of them localized in the mitochondria and its effect is dose-and time-dependent. This study analyzed the effect of distinct F concentrations and exposure periods on the mitochondrial activity of complex I-III and II-III in the liver. Thirty-six 21-day-old male Wistar rats were divided into 2 groups (n ¼ 18) according to the duration of the treatment (20 or 60 days). They were subdivided into 3 subgroups (n ¼ 6) according to the concentration of F (0 mg/L, 15 mg/L or 50 mg/L). After the experimental periods, the animals were anesthetized, liver mitochondria were isolated and stored for activity analyses. The determination of complexes II-III and I-III was based on the reduction of cytochrome c 3þ to cytochrome c 2þ performed spectrophotometrically. Bioinformatics analyses were performed using data from a previous study (Pereira et al., 2018). The mitochondrial complex I-III was significantly activated in the groups treated with 50 mgF/L for 20 days and 15 mgF/L for 60 days. The complex II-III was significantly reduced in the group treated with the higher F dose for 60 days. The networks indicated more changes in mitochondrial proteins in the group treated with the higher dose for 20 days; the reduction is probably linked to the activation of the complex I-III. The reduction in the complex II-III upon exposure to the higher F dose in the long term might be part of an adaptative mechanism of the body to counteract the deleterious effects of this ion on the energy metabolism.

Alterations in Mitochondrial Oxidative Phosphorylation System: Relationship of Complex V and Cardiac Dysfunction in Human Heart Failure

“…Our results show a general overexpression in complex I while maintaining complex II without alteration. Previous studies have observed increased activity in complex I induced by fluoride along with a reduction in complex II [ 37 ]. These authors indicate that increased activity in complex I could lead to increased ATP and ROS production, and a reduction in complex II could suggest an attempt to reduce energy production to combat increased ROS [ 37 ].…”

“…Previous studies have observed increased activity in complex I induced by fluoride along with a reduction in complex II [ 37 ]. These authors indicate that increased activity in complex I could lead to increased ATP and ROS production, and a reduction in complex II could suggest an attempt to reduce energy production to combat increased ROS [ 37 ]. Enhanced production of ROS can be highly detrimental and consequently damage macromolecules within mitochondria, including lipids, proteins, and mtDNA [ 38 , 39 , 40 ].…”

“…Enhanced production of ROS can be highly detrimental and consequently damage macromolecules within mitochondria, including lipids, proteins, and mtDNA [ 38 , 39 , 40 ]. The alterations described here could be part of an adaptive mechanism of the organism to combat the deleterious effects of the increase in ROS [ 37 ].…”

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

“…Reducing some of these key proteins may indicate a desperate attempt to maintain balance in OXPHOS and avoid the activation of apoptotic pathways. Further, we also noticed that the activity of all the complexes decreased upon exposure to the higher dose of NaF [ 59 – 61 ], increasing the release of superoxide anions and thus increasing ROS levels [ 26 ]. The oxidative stress induced by NaF provokes the dysfunction of the mitochondrial complexes in the skeletal muscle leading to muscle atrophy.…”

Prolonged exposure to high fluoride levels during adolescence to adulthood elicits molecular, morphological, and functional impairments in the hippocampus

“…However, a recently published systematic review by our group 11 pointed out that the level considered optimum by the WHO is not associated with neurological disorders, whereas higher levels may be associated with lowering the intelligence quotient. To address this issue, we used an experimental design to investigate the association of a low fluoride dose, considered representative of artificial fluoridation of the domestic water supply, and a high fluoride dose, representative of fluoride endemic regions where fluorosis is common, based on molecular, morphological and functional aspects in mice exposed from adolescence to adulthood 12 – 16 . This window of exposure makes this investigation even more relevant due to the widespread knowledge that at this stage, the central nervous system (CNS) is still developing, presenting similar neurodevelopment events that occur in human children, adolescents and young adults.…”