Comprehensive in vitro and in ovo assessment of cytotoxicity: Unraveling the impact of sodium fluoride, xylitol, and their synergistic associations in dental products.

Over the past several decades, dental health products containing fluoride have been widely employed to mitigate tooth decay and promote oral hygiene. However, concerns regarding the potential toxicological repercussions of fluoride exposure have incited continuous scientific inquiry. The current study investigated the cytotoxicity of sodium fluoride (NaF) and xylitol (Xyl), both individually and in combination, utilizing human keratinocyte (HaCaT) and osteosarcoma (SAOS-2) cell lines. In HaCaT cells, NaF decreased proliferation in a concentration-dependent manner and induced apoptosis-related morphological changes at low concentrations, whereas Xyl exhibited dose-dependent cytotoxic effects. The combination of NaF and Xyl reduced cell viability, particularly at higher concentrations, accompanied by apoptosis-like morphological alterations. Sub-cytotoxic NaF concentrations (0.2%) significantly affected caspase activity and the expression of pro-apoptotic genes. Conversely, Xyl demonstrated no discernible effect on these biological parameters. In SAOS-2 cells, NaF increased proliferation at high concentrations, contrasting with Xyl's concentration-dependent cytotoxic effects. The combination of NaF and Xyl had a minimal impact on cell viability. Sub-cytotoxic NaF concentrations did not influence caspase activity or gene expression, while Xyl induced dose-dependent morphological alterations, increased caspase activity, and upregulated pro-apoptotic gene expression. In ovo experiments on the chorioallantoic membrane (CAM) revealed that only NaF induced irritant effects, suggesting potential vascular adverse outcomes. This study advocates for the combined use of NaF and Xyl, highlighting their cytotoxicity benefits in healthy cells while maintaining safety considerations for tumor cells.

Acute, Fatal, Presumptive Xylitol Toxicosis in Cape Sugarbirds ( Promerops cafer).

Twenty-nine wild Cape sugarbirds ( Promerops cafer) died acutely after ingestion of a homemade xylitol nectar solution from a bird feeder. The most aggressive feeders were first affected. Most birds showed clinical signs within 15 minutes of nectar ingestion, including incoordination, weakness, falling from perches, collapse, and death. A few birds showing clinical signs seemed to spontaneously recover and fly away. Full necropsy examinations done on 27 birds were hampered by freezing artifact and autolysis, but results indicated death was caused by the consequences of acute hypoglycemia. A presumptive diagnosis of xylitol toxicity was made based on the history, clinical signs, and absence of other obvious causes of death. This is potentially the first record of xylitol toxicity in wild birds.

Xylitol induces cell death in lung cancer A549 cells by autophagy.

Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells.

Dynamic sieving capillary electrophoresis analysis of xylitol selenite-induced apoptosis in SMMC-7221 cells.

DNA ladder fragments, regarded as a biochemical hallmark of apoptosis, have been separated quickly and successfully by capillary electrophoresis. Inter-nucleosomal DNA fragmentations induced by xylitol selenite were determined for the first time, while hydroxypropylmethylcellulose (HPMC) was served as the sieving matrix in dynamic sieving capillary electrophoresis. The calibration curve (r(2) = 0.991) was established and multiples of two different nucleosomes (140 and 180 bp) were formed in the presence of xylitol selenite. Selenium compounds inhibited carcinogenesis in animal models, SMMC-7221 cells and several other cells by increasing apoptosis. The described method was useful in elucidating the anticancer activities of xylitol selenite and other selenium compounds, which was more effective to detect small fragments than slab gel electrophoresis.

Safety assessment of nebulized xylitol in beagle dogs.

Xylitol, a potential cystic fibrosis treatment, lowers the salt concentration of airway surface liquid and enhances innate immunity of human airways. The study objective was to evaluate the potential toxicity/recovery from a 14-consecutive day (7 days/week), facemask inhalation administration of nebulized xylitol solution in Beagle dogs. Aerosolized xylitol was generated through three Aerotech II nebulizers operating at approximately 40 psi driving pressure. Test article groups were exposed to the same concentration of aerosolized xylitol for 1, 0.5, or 0.25 h for the high, mid, and low exposures, respectively. A control group was exposed for 1 h to a nebulized normal saline solution. Animals were sacrificed the day following the last exposure or subsequently after 14 non-exposure days. Study endpoints included clinical observations, body weights, ophthalmology, and physical examinations, food consumption, clinical pathology, urinalyses, organ weights, and histopathology. Mean xylitol aerosol concentrations for all groups were approximately 3.5 mg/l. Mean total deposited doses to the pulmonary region were estimated as 21, 11, and 5 mg/kg, for the high-, mid-, and low-exposure groups, respectively. All dogs survived to the scheduled necropsy. No treatment-related findings were observed due to xylitol exposure in any end point examined. Lung findings (mild interstitial infiltration, macrophage hyperplasia, alveolitis, and bronchitis) were consistent among exposed and control groups. No exposure-related effect of xylitol in any parameter assessed was seen during or after the 14-day exposure in Beagle dogs. The No Observed Effect Level was the high-exposure level and suggests that inhaled xylitol is safe for clinical administration.

Regioselective synthesis and biological profiling of butyric and phenylalkylcarboxylic esters derivated from D-mannose and xylitol: influence of alkyl chain length on acute toxicity.

Regiospecific synthesis of 12 novel n-butyric and phenylalkylcarboxylic monoesters of mannose and xylitol was achieved. The strategy adopted, avoided a tedious intramolecular transesterification step, previously described for the synthesis of analogous compounds and permitted the facile synthesis of a new generation of stable derivatives. The general tolerance of the drugs has been assayed after intravenous administration of a bolus dose into mice. Monobutyric esters showed a low toxicity commensurate with the requirements for future development. A relationship was observed between chain length and toxicity. In contrast, phenylacetic, 3-phenylpropionic and 4-phenylbutyric esters were found to be toxic. Phenylbutyric esters induced marked and specific neuromuscular damage. Preliminary biological investigations of the new series of monobutyric esters showed them to retain the benificial biological properties of butyric acid whilst remaining relatively non toxic. They induced an inhibition of in vitro proliferation of 10 human cases of de novo acute myeloid leukemia (AML) primary cultures and AML established cell lines. AML blasts growth appeared to be blocked and cell differentiation was established. Transcription and expression of maturation markers and finally apoptosis were observed. Moreover, human gamma-chain hemoglobin (HbF) synthesis in erythroleukemia cells was stimulated by monobutyric esters. Mannose and xylitol butyric derivatives would appear to have exciting potential in treatment of beta-Hemoglobinopathies, sickle cell anemia and cancer.

Early biochemical and morphological changes of the rat adrenal medulla induced by xylitol.

Long-term administration of high doses of xylitol and other polyols in rats has been associated with an increase in adrenal medullary hyperplasia and neoplasia. In order to exclude age-related factors and to differentiate between unspecific stress reactions and direct effects of the compound administered, a model was developed for quantifying early adrenomedullary responses. Male SD rats were fed xylitol (10% or 20% in the diet) for 2 and 8 weeks, and early biochemical changes were correlated with a stereological analysis of the adrenal medulla. At first, the in vivo rate of catecholamine (CA) biosynthesis was slightly decreased (at 2 weeks). This was followed by an increase in dopamine-beta-hydroxylase (DBH) activity (at 8 weeks). By that time, the total chromaffin cell volume had increased and the number of chromaffin cells per reference volume had decreased in a dose-dependent way. The total number of chromaffin cells per adrenal gland showed a distinct tendency towards an increase. Adrenal epinephrine and norepinephrine contents were not altered, and both tyrosine hydroxylase and phenylethanolamine-N-methyltransferase activities remained unchanged. These data suggest that continued xylitol administration evoked an inhibitory effect on CA synthesis that, together with stimulation of the adrenal medulla brought about by the compound, resulted in compensatory medullary hypertrophy and hyperplasia.

The effects of lifetime feeding studies on patterns of senile lesions in mice and rats.

Data from lifetime feeding studies in mice and rats comparing controls to three doses of Xylitol, to Sorbitol, and to sucrose are examined to illustrate the thesis that the occurrence of some tumors is often confounded with other lesions and even other tumors in lifetime feeding studies. It is suggested that it may be impossible to test whether a treatment is a "carcinogen" in the presence of such biological confounding.