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.2022 Sep 30;73(3):207-222.
doi: 10.2478/aiht-2022-73-3650. eCollection 2022 Sep 1.

Redox and biometal status in Wistar rats after subacute exposure to fluoride and selenium counter-effects

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Redox and biometal status in Wistar rats after subacute exposure to fluoride and selenium counter-effects

Jelena Radovanović et al. Arh Hig Rada Toksikol..

Abstract
in English, Croatian

This study aimed to investigate the effect of 150 mg/L sodium fluoride (NaF) on redox status parameters and essential metals [copper (Cu), iron (Fe), and zinc (Zn)] in the blood, liver, kidney, brain, and spleen of Wistar rats and to determine the protective potential of selenium (Se) against fluoride (F-) toxicity. Male Wistar rats were randomly distributed in groups of five (n=5) receiving tap water (control) or water with NaF 150 mg/L, NaF 150 mg/L + Se 1.5 mg/L, and Se 1.5 mg/L solutionsad libitum for 28 days. Fluorides caused an imbalance in the redox and biometal (Cu, Fe, and Zn) status, leading to high superoxide anion (O2 .-) and malondialdehyde (MDA) levels in the blood and brain and a drop in superoxide dismutase (SOD1) activity in the liver and its increase in the brain and kidneys. Se given with NaF improved MDA, SOD1, and O2 .- in the blood, brain, and kidneys, while alone it decreased SH group levels in the liver and kidney. Biometals both reduced and increased F- toxicity. Further research is needed before Se should be considered as a promising strategy for mitigating F- toxicity.

Cilj ovog istraživanja bio je utvrditi djelovanje 150 mg/L natrijevog fluorida (NaF) na redoks-status i koncentracije esencijalnih elemenata [bakar (Cu), željezo (Fe) i cink (Zn)] u krvi, jetri, bubrezima, mozgu i slezeni Wistar štakora te mogući zaštitni učinak selena (Se) od toksičnosti prouzročene fluoridom (F-). Mužjaci Wistar štakora nasumično su razvrstani u četiri skupine (n=5), nakon čega su 28 dana konzumirali običnu vodu ili vodu s otopinom NaF 150 mg/L, NaF 150 mg/L + Se 1,5 mg/L ili Se 1,5 mg/L. Izloženost fluoridu dovela je do poremećaja redoks-parametara i koncentracija istraživanih biometala. Utvrđene su povišene razine superoksid aniona (O2.-) i malondialdehida (MDA) u krvi i mozgu, smanjena aktivnost superoksid dismutaze (SOD1) u jetri te njezin porast u mozgu i bubrezima. Nadomjesni Se u kombinaciji s NaF pozitivno je utjecao na razine MDA, SOD1 i O2.- u krvi, mozgu i bubrezima, a sâm Se smanjio je razine SH skupina u jetri i bubrezima. Izloženost fluoridu uzrokovala je sniženje, ali i porast koncentracija biometala. Nužna su dodatna istraživanja kako bi se ispitali antioksidacijski učinci Se na toksičnost izazvanu F-.

Keywords: Cu; Fe; MDA; NaF; O2.-; SOD1; Se; Zn; natrijev fluorid; oksidacijski stres; oxidative stress; sodium fluoride; subacute toxicity; subakutna toksičnost.

© 2022 Jelena Radovanović, Biljana Antonijević, Katarina Baralić, Marijana Ćurčić, Danijela Đukić-Ćosić, Zorica Bulat, Dragana Javorac, Aleksandra Buha Đorđević, Jelena Kotur-Stevuljević, Emina Sudar-Milovanović, Evica Antonijević Miljaković, Miloš Beloica, and Zoran Mandinić, published by Sciendo.

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Conflict of interest statement

Conflicts of interest

None to declare.

Figures

Figure 1
Figure 1
Median (and range) of water consumption (mL/day) by groups of Wistar rats exposed to fluoride and/or selenium for 28 days.* p<0.05;*** p<0.001 – significant differences compared to control (Kruskal-Wallis followed by Dunn’s test). F group – exposed to sodium fluoride alone (150 mg/L); Se group – exposed to sodium selenite alone (1.5 mg/L); F+Se group – exposed to the combination of F and Se at the same concentrations
Figure 2
Figure 2
Blood redox parameters in Wistar rats exposed to fluoride 150 mg/L and/or selenium 1.5 mg/L through drinking water for 28 days. a) O2.- – superoxide anion (μmol/min/L); b) TOS – total oxidative status (μmol/L); c) SOD1 – superoxide dismutase activity (U/L); d) SH – total thiol groups (mmol/L); e) MDA – malondialdehyde (μmol/L).* # p<0.05;** aa p<0.01 – significant differences from control group are indicated by *, from the Se group by#, from the F group bya (one-way ANOVA followed by Fisher’s LSD and Kruskal-Wallis test followed by Dunn’spost-hoc test). The line inside of the box presents the median, the box presents interquartile range (25–75 %). End limiters present minima and maxima
Figure 3
Figure 3
Liver redox parameters in Wistar rats exposed to fluoride 150 mg/L and/or selenium 1.5 mg/L through drinking water for 28 days. a) O2.- – superoxide anion (μmol/min/g protein); b) TOS – total oxidative status (μmol/g protein); c) SOD1 – superoxide dismutase activity (U/g protein); d) SH – total thiol groups (mmol/g protein); e) MDA – malondialdehyde (μmol/g protein).* p<0.05;** ## p<0.01 – significant differences from control group are indicated by *, from the Se group by# (one-way ANOVA followed by Fisher’s LSD and Kruskal-Wallis test followed by Dunn’spost-hoc test). The line inside of the box presents the median, the box presents interquartile range (25–75 %). End limiters present minima and maxima
Figure 4
Figure 4
Spleen redox parameters in Wistar rats exposed to fluoride 150 mg/L and/or selenium 1.5 mg/L through drinking water for 28 days. a) O2.- – superoxide anion (μmol/min/g protein); b) TOS – total oxidative status (μmol/g protein); c) SOD1 – superoxide dismutase activity (U/g protein), d) SH – total thiol groups (mmol/g protein); e) MDA – malondialdehyde (μmol/g protein).a p<0.05 – significant differences from the F group are indicated bya (One-way ANOVA followed by Fisher’s LSD and Kruskal-Wallis test followed by Dunn’spost-hoc test). The line inside of the box presents the median, the box presents interquartile range (25–75 %). End limiters present minima and maxima
Figure 5
Figure 5
Brain redox parameters in Wistar rats exposed to fluoride 150 mg/L and/or selenium 1.5 mg/L through drinking water for 28 days. a) O2.- – superoxide anion (μmol/min/g protein); b) TOS – total oxidative status (μmol/g protein); c) SOD1 – superoxide dismutase activity (U/g protein); d) MDA – malondialdehyde (μmol/g protein).* # a p<0.05;### p<0.001 – significant differences from control group are indicated by *, from the Se group by#, from the F group bya (one-way ANOVA followed by Fisher’s LSD and Kruskal-Wallis test followed by Dunn’spost-hoc test). The line inside of the box presents the median, the box presents interquartile range (25–75 %). End limiters present minima and maxima
Figure 6
Figure 6
Kidney redox parameters in Wistar rats exposed to fluoride 150 mg/L and/or selenium 1.5 mg/L through drinking water for 28 days. a) O2.-– superoxide anion (μmol/min/g protein); b) TOS – total oxidative status (μmol/g protein); c) SOD1 – superoxide dismutase activity (U/ g protein); d) SH – total thiol groups (mmol/g protein); e) MDA – malondialdehyde (μmol/g protein).* # p<0.05;** p<0.01;*** p<0.001;**** p<0.0001 – significant differences from control group are indicated by *, from the Se group by# (one-way ANOVA followed by Fisher’s LSD and Kruskal-Wallis test followed by Dunn’spost-hoc test). The line inside of the box presents the median, the box presents interquartile range (25–75 %). End limiters present minima and maxima
Figure 7
Figure 7
Mean (±SD) liver, spleen, brain, and kidney fluoride levels (mg/kg) in Wistar rats exposed to fluoride (150 mg/L) and/or selenium (1.5 mg/L) through drinking water for 28 days.a p<0.05; ** p<0.01; **** p<0.0001 – significant differences from control are indicated by *, from the F group bya (one-way ANOVA followed by Fisher’s LSD)
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