Full length article
Selenium may suppress peripheral blood mononuclear cell apoptosis by modulating HSP70 and regulate levels of SIRT1 through reproductive hormone secretion and oxidant stress in women suffering fluorosis

https://doi.org/10.1016/j.ejphar.2020.173098Get rights and content

Abstract

Excessive taking fluoride (F) causes severe damage to reproductive system through stimulation of apoptosis and oxidant stress. Selenium (Se) may promote anti-oxidant enzymes and invert cell apoptosis. The aim of this study was to investigate the effect of Se on peripheral blood mononuclear cell (PBMC) apoptosis and oxidant stress in women with fluorosis. Sixty women were divided into three groups according to serum and urine fluoride and hair Se as High F + high Se group, High F group and Control group. The activities of anti-oxidant enzymes, malondialdehyde (MDA) and Se were measured. The levels of sirtuin type 1 (SIRT1), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by enzyme-linked immune sorbent assay (ELISA) kits. The expression of protein and apoptosis rate were detected by Western blot and Flow cytometry. The levels of E2, anti-oxidant enzymes in High F group were significantly lower than that in Control group, while the levels of SIRT1 and MDA were significantly higher. The levels of anti-oxidant enzymes and heat shock protein 70 (HSP70) were significantly increased in High Se + high F group while the expression of caspase-3 was significantly increased in high F group. The levels of LH and FSH in serum were significantly increased in High F group and High Se + high F group. Therefore, Se alleviates apoptosis induced by F through improving the expression of HSP70 and reduces oxidative stress by regulating levels of SIRT1 and anti-oxidant enzymes, and the secretion of certain reproductive hormones.

Introduction

Fluorosis is a worldwide environmental health problem caused by excessive exposure to fluoride (F). Fluoride (F) is widely used as an additive in toothpaste or industrial raw materials. The safe range of fluoride is relatively low, and excessive fluoride intake (fluorosis) may cause severe damage to tissues and organs, especially the tissues in the reproductive system. It was reported that fluorosis caused malfunction of the female reproductive system in people who had lived in fluorosis endemic areas for a long time (Liang et al., 2016). There is also evidence showing the association of higher concentration of fluoride and significantly more miscarriages (Moghaddam et al., 2018).

Selenium (Se), like fluoride, is also an essential trace element in humans. The biological functions of Se are recognized for its catalytic and antioxidant activities. Several studies have demonstrated the beneficial effect of Se on reproductive function in females (Kommisrud et al., 2005; Xiong et al., 2018). It is however unknow whether Se may improve reproductive function in women with fluorosis.

Fluoride is well documented to increase reactive oxygen species (ROS) production and induce apoptosis (Lou et al., 2019; Peng et al., 2019). Sirtuins are a family of NAD + -dependent histone deacetylase that involved in aging and, oxidative stress. In mammalian cells, Sirtuin type 1 (SIRT1) promotes antioxidant enzymes to detoxify the effects of reactive oxygen species (ROS)-caused apoptosis (Kong et al., 2019). However, no clear evidence to link SIRT1, Se and fluorosis in the pathophysiological process of fluorosis-caused reproductive dysfunction. The aim of this study, therefore, was to investigate the effect of Se on SIRT1 to improve reproductive system function in female fluorosis patients.

Section snippets

Subjects and sample collection

There were three groups of subjects in this research. A total of 20 female fluorosis patients from the area with high environmental selenium levels (Li et al., 2019)(Ziyang County of Shaanxi province, China) were included in the Group 1 (High Se + high F) group. Twenty adult healthy women volunteers from Xi'an city, where the environmental selenium levels were at normal range, were included in Group 2 as the normal control group. Another twenty women fluorosis patients from Hanbin district,

The age of women in three groups

Of the 60 women recruited in this study, means of ages of all women in each group were shown in Table 1. There was no significant difference in ages of women among all three groups.

Selenium levels in blood and hair

The concentrations of selenium in blood (serum) and hair were significantly higher in high Se + high F group than that in High F or control group (P < 0.01, Fig. 1). The concentrations of selenium in blood and hair of High F group were slightly higher than that of Control group without statistical significance (P

Discussion

Fluoride is an important industrial product in addition its use in toothpaste. Taking in too much fluoride leads to fluorosis in patients showing not only teeth and bone injuries but also reproductive dysfunction in females (Navve et al., 2013; Zhao et al., 2015). Many studies have found that SIRT1 played a key role in regulating reproductive hormone secretion (Chen et al., 2019a,b). This study was designed to investigate the effect of fluorosis with or without Se on oxidative stress, apoptosis

Conclusion

In conclusion, high level of F increases apoptosis rate and the expression of caspase-3 with a decrease in the activities of antioxidant enzymes and level of E2, and an increase in the expression of SIRT1, serum FSH and LH. High level of Se attenuates the toxic effects of high F by increasing the level of HSP-70. Se may be able to quench F-induced free radical generation showing anti-apoptotic effects. Indeed, the reduction of SIRT1, LH and FSH and the increase in E2 were observed in High

CRediT authorship contribution statement

Wenrong Li: Writing - review & editing, Conceptualization, Methodology, Writing - review & editing, Validation. Qun Chen: Validation, Writing - review & editing. Chen Chen: Validation, Writing - original draft, Writing - review & editing. Zhaoheng Dong: Writing - review & editing.

Declaration of competing interest

The authors declare no potential conflicts of interest.

Acknowledgements

Financial support for this work was received from National Natural Science Foundation of China (grant number 81673115), Huimin project of Ministry of Science and Technology of China (grant number 2012GS610101), and Department of Health of Shaanxi Province (grant number 2018D050) and the International Cooperation Foundation of Shaanxi province(2020KW-057).

References (38)

  • H. Zhang et al.

    Kuntai capsule attenuates premature ovarian failure through the PI3K/AKT/mTOR pathway

    J. Ethnopharmacol.

    (2019)
  • M.X. Zhao et al.

    Fluoride exposure, follicle stimulating hormone receptor gene polymorphism and hypothalamus-pituitary-ovarian Axis hormones in Chinese women

    Biomed. Environ. Sci.

    (2015)
  • W. Zheng et al.

    Effects of zearalenone and its derivatives on the synthesis and secretion of mammalian sex steroid hormones: a review

    Food Chem. Toxicol.

    (2019)
  • K.M. Abdullah et al.

    Anti-diabetic study of vitamin B6 on hyperglycaemia induced protein carbonylation, DNA damage and ROS production in alloxan induced diabetic rats

    Toxicol. Res-UK.

    (2019)
  • A.R. Bellin et al.

    Impaired SIRT1 activity leads to diminution in glomerular endowment without accelerating age-associated GFR decline

    Phys. Rep.

    (2019)
  • X. Chen et al.

    Receptor for advanced glycation end products reveals a mechanism regulating thyroid hormone secretion through the SIRT1/Nrf2 pathway

    J. Cell. Biochem.

    (2019)
  • C.R. Chowdhury et al.

    Spatial distribution mapping of drinking water fluoride levels in Karnataka, India: fluoride-related health effects

    Perspect. Public. Heal.

    (2016)
  • S. Dodig et al.

    Hallmarks of senescence and aging

    Biochem. Med.

    (2019)
  • S. He et al.

    Effects of selenium on peripheral blood mononuclear cell membrane fluidity, interleukin-2 production and interleukin-2 receptor expression in patients with chronic hepatitis

    World J. Gastroenterol.

    (2004)
  • Cited by (13)

    • Alleviating effects of selenium on fluoride-induced testosterone synthesis disorder and reproduction toxicity in rats

      2022, Ecotoxicology and Environmental Safety
      Citation Excerpt :

      The protein expression level of P450scc was enhanced markedly in F + SeIII group compared to the F group (p < 0.05). The reproductive health problems caused by F exposure have attracted the attention of many researcher (Li et al., 2020; Ma et al., 2017). Male sterility is closely related to sperm quality, and F has obvious toxic effects on sperm.

    • Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis

      2022, Chemico-Biological Interactions
      Citation Excerpt :

      More experimental works matching these studies are described in Tables 1 and 2. A higher level of F− induced-ROS was also reported to disrupt ovarian development, reducing the number of mature follicles as observed in rats [54,55] humans [56,57], and zebrafish [58]. Therefore, excessive generation of ROS upon F− exposure not only affects the cellular mechanisms but also affects the organ systems.

    • Comprehensive proteomic analysis to elucidate the anti-heat stress effects of nano-selenium in rainbow trout (Oncorhynchus mykiss)

      2022, Ecotoxicology and Environmental Safety
      Citation Excerpt :

      HSPs essentially block all apoptotic pathways, most of which involve inhibiting the activation of caspases (Lanneau et al., 2007). The upregulation of the expression of HSPs apparently plays a more effective role against apoptosis in the presence of high Se levels (Li et al., 2020). This is consistent with our results, which suggested that nano-Se improves apoptosis by upregulating the expression of Hsp70, Hsp90a.1, Hspa8, and Dnajb1.

    View all citing articles on Scopus
    1

    These authors contributed equally to this manuscript.

    View full text