Fluoride is ubiquitously present throughout the world. It is released from minerals, magmatic gas, and industrial processing, and travels in the atmosphere and water. Exposure to low concentrations of fluoride increases overall oral health. Consequently, many countries add fluoride to their public water supply at 0.7–1.5 ppm. Exposure to high concentrations of fluoride, such as in a laboratory setting often exceeding 100 ppm, results in a wide array of toxicity phenotypes. This includes oxidative stress, organelle damage, and apoptosis in single cells, and skeletal and soft tissue damage in multicellular organisms. The mechanism of fluoride toxicity can be broadly attributed to four mechanisms: inhibition of proteins, organelle disruption, altered pH, and electrolyte imbalance. Recently, there has been renewed concern in the public sector as to whether fluoride is safe at the current exposure levels. In this review, we will focus on the impact of fluoride at the chemical, cellular, and multisystem level, as well as how organisms defend against fluoride. We also address public concerns about fluoride toxicity, including whether fluoride has a significant effect on neurodegeneration, diabetes, and the endocrine system.

Principles of fluoride toxicity and the cellular response: a review.

Intestinal barrier damage involved in intestinal microflora changes in fluoride-induced mice.

Silver nanoparticles (AgNPs) have been widely produced for different industrial purposes. Recently, biogenic synthesis of AgNPs has emerged although the extent of effects from exposure, oral exposure in particular, to nanomaterials synthesized in such a manner remains elusive. The main objective of this study was to evaluate the effects of oral administration of a dose of 50 mg/Kg body weight AgNPs biosynthesized in baker's yeast (Saccharomyces cerevisiae) over a period of eight weeks on the reproductive performance and the possibility of a protective effect through co-administration of morin. Forty-eight male Sprague-Dawley rats were used in four experimental groups (control, morin-treated group, AgNP-treated, and AgNP + morin co-treatment). AgNPs produced no significant alteration in daily food intake or body weight. Both the absolute and relative testicular weights were significantly reduced but not the epididymal weight. Also, serum levels of urea, creatinine, uric acid, and liver enzymes were significantly elevated. Furthermore, AgNPs significantly downregulated the hypothalamic-pituitary-gonadal axis. This corresponds to lower motility and viability percent, reduced sperm concentration, and a higher abnormality ratio as well as a prominent alteration in the blood-testis barrier (BTB) and testicular histology and induction of testicular apoptosis and oxidative stress. The supplementation of morin evidently restored most of the reproductive characters to its physiological range. We can conclude that exposure to the biologically synthesized AgNPs for an extended period of time has proven to be a health risk that can be ameliorated via oral administration of some bioactive agents including morin.

Morin ameliorates the testicular apoptosis, oxidative stress, and impact on blood–testis barrier induced by photo-extracellularly synthesized silver nanoparticles

Wound dressings with asymmetric wettability surfaces can effectively prevent bacterial colonization and tissue dehydration and have shown great potential for diabetic wound healing applications. Ho...

Asymmetric Wettable Composite Wound Dressing Prepared by Electrospinning with Bioinspired Micropatterning Enhances Diabetic Wound Healing

Age-related arabinoxylan hydrolysis and fermentation in the gastrointestinal tract of broilers fed wheat-based diets

The present study aimed to evaluate the effect of fluoride (F) on spermatogenesis in male rats. F− at 50 and 100 mg/L was administered for 70 days, after which the testicular and epididymis tissues were collected to observe the histopathological structure under a light microscope. The ultrastructure of the testis and sperm was also examined via transmission electron microscopy. The apoptosis of spermatogenic cells was measured through terminal deoxynucleotidyl transferase dUTP nick end labeling staining. The expression of proliferation factors, namely, proliferating cell nuclear antigen (PCNA) and Ki-67, in the testicular and epididymis tissues, were assayed through immunohistochemistry. F− at 50 and 100 mg/L significantly damaged the structure of the testis and epididymis, and the testis and sperm ultrastructure exhibited various changes, including mitochondrial swelling and vacuolization, and apsilated and raised sperm membrane. F treatment significantly increased spermatogenic cell apoptosis in the testis. PCNA (P < 0.01) and Ki-67 (P < 0.01) also presented positive expression in the testis. By comparison, no significant changes occurred in the epididymis. In summary, excessive F intake results in spermatogenesis dysfunction by damaging the testicular structure and inducing spermatogenic cell apoptosis in male rats. The positive expression level of PCNA and Ki-67 was a good response to spermatogenesis dysfunction.

Positive PCNA and Ki-67 Expression in the Testis Correlates with Spermatogenesis Dysfunction in Fluoride-Treated Rats

Mitochondrial respiratory chain damage and mitochondrial fusion disorder are involved in liver dysfunction of fluoride-induced mice.

Mitochondrial respiratory chain complex abnormal expressions and fusion disorder are involved in fluoride-induced mitochondrial dysfunction in ovarian granulosa cells.

This study aimed to determine the effect of excessive fluoride (F) on the morphological characteristics of the small intestine and the contents of serum cytokines in rats A total of 48 3-week-old healthy female Sprague-Dawley rats were randomly divided into four groups (n = 12) The control group was given deionized distilled water, while the F treatment groups were treated with water containing 25, 50, and 100 mg F−/L After 70 days of treatment, the duodenum, the jejunum, and the ileum were collected to measure the developmental parameters and the distribution of intestinal glycoproteins, goblet cells, and mast cells through Pannoramic Viewer, Periodic Acid-Schiff (PAS) staining, Alcian blue and periodic acid-Schiff (AB-PAS) staining, and toluidine blue staining, respectively The contents of cytokines, namely, interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α, in serum were detected via enzyme-linked immunosorbent assay (ELISA) Results showed that the villus height, crypt depth, villus height to crypt depth ratio, goblet cells, glycoproteins, and mast cells of the small intestine significantly decreased (P < 005 or P < 001) in the F treatment group The contents of IL-1β, IL-2, IL-6, and TNF-α were significantly lower in the F treatment group than in the control group (P < 005 or P < 001) In summary, excessive F intake impaired intestinal development and immune function by decreasing the developmental parameters and the distribution of immune cells, glycoproteins, and cytokines

Effect of Fluoride on Small Intestine Morphology and Serum Cytokine Contents in Rats

Intestinal microflora plays a key role in maintaining the homeostasis between immune and host health. Here, we reported the fluoride-induced changes of rectal structure and microflora in mice. The morphology of rectal tissue was observed by hematoxylin and eosin staining. The rectal development parameters (the thickness of mucosa, intestinal gland and muscle layer) were evaluated. The proliferation of rectal epithelial cells was evaluated via BrdU labeling. The distribution of goblet, glycoprotein and mast cell were evaluated by specific staining. Rectal microflora was detected using 16S rRNA high-throughput sequencing. The results showed that the rectal structure was seriously damaged and the proliferation of rectal epithelial cells was significantly inhibited by fluoride. The distribution of goblet cells, glycoprotein and mast cells decreased significantly after fluoride exposure. The relative richness of microfloras was changed after fluoride treatment, such as increased Bacteroidetes and decreased Firmicutes. In summary, this study indicated that excessive fluoride damages the intestinal structure, disturbs the intestinal micro-ecology and causes intestinal microflora disorder in mice. Findings mentioned in the present study enrich a new scope for elucidating fluoride toxicity from intestinal homeostasis.

Shi-quan Zhu

Papers

Positive PCNA and Ki-67 Expression in the Testis Correlates with Spermatogenesis Dysfunction in Fluoride-Treated Rats

Mitochondrial respiratory chain damage and mitochondrial fusion disorder are involved in liver dysfunction of fluoride-induced mice.

Mitochondrial respiratory chain complex abnormal expressions and fusion disorder are involved in fluoride-induced mitochondrial dysfunction in ovarian granulosa cells.

Effect of Fluoride on Small Intestine Morphology and Serum Cytokine Contents in Rats

Fluoride-induced rectal barrier damage and microflora disorder in mice