Fluoride-induced apoptosis in non-skeletal tissues of experimental animals: A systematic review and meta-analysis.

Different studies have suggested that fluoride can induce apoptosis in non-skeletal tissues, however, evidence from these experimental studies is still controversial. This meta-analysis aims to clarify the mechanism of fluoride-induced apoptosis in non-skeletal tissues of experimental animals. Primary studies which measured apoptosis were identified through exhaustive database searching in PubMed, Embase, Web of Science Core Collection, Scopus, and references of included studies. A random effects model with standardized mean difference (SMD) was used for meta-analyses. The heterogeneity of the studies was evaluated using Higgin's I2 statistics. The risk of bias and publication bias were assessed using the SYRCLE's risk of bias tool and Egger's test, respectively. There was an increase in total apoptotic cells, and the expression of Bax, Bax/Bcl-2 ratio, caspase-3, caspase-8, caspase-9, Cyt c, and p53, and a decrease in the expression of Bcl-2 in the fluoride-treated groups as compared to the control groups. However, there was no evidence of a difference in the expression of APAF-1 in the two groups. The subgroup analysis highlighted the role of the intervention period in modification of the apoptotic effect of fluoride and that the susceptibility and tolerance of different animal species and tissues vary. Meta-regression analysis indicated that the studies' effect size for total apoptotic cells was influenced by animal species and that of Bax by the sample source. The results of this meta-analysis revealed that fluoride causes apoptosis by up-regulating caspase-3, -8, and -9, Cyt c, p53, Bax, and down-regulating Bcl-2 with a concomitant up-regulation of the Bax/Bcl-2 ratio.

Fluoride induced metabolic disorder of endothelial cells.

Endemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.

Antioxidant Phytochemicals for the Prevention of Fluoride-Induced Oxidative Stress and Apoptosis: a Review.

Fluorosis is a major public health problem globally. The non-availability of specific treatment and the irreversible nature of dental and skeletal lesions poses a challenge in the management of fluorosis. Oxidative stress is known to be one of the most important mechanisms of fluoride toxicity. Fluoride promotes the accumulation of reactive oxygen species by inhibiting the activity of antioxidant enzymes, resulting in the excessive production of reactive oxygen species at the cellular level which further leads to activation of cell death processes such as apoptosis. Phytochemicals that act as antioxidants have the potential to protect cells from oxidative stress. Evidence confirms that clinical symptoms of fluorosis can be mitigated to some extent or prevented by long-term intake of antioxidants and plant products. The primary purpose of this review is to examine recent findings that focus on the amelioration of fluoride-induced oxidative stress and apoptosis by natural and synthetic phytochemicals and their molecular mechanisms of action.

Contraceptive use among women with a history of induced abortion: findings from a national sample of sexually active, non-pregnant women in Ghana.

OBJECTIVE: The aim of the study was to examine the relationship between a history of induced abortion and current use of contraception among reproductive-aged women in Ghana. METHODS: The analysed data were a weighted sample of 6544 sexually active, non-pregnant women aged 15-49 years, obtained from the 2014 Ghana Demographic and Health Survey. Survey logistic regression analysis was used to estimate the odds of currently using any contraception and of using a modern method of contraception, given a history of induced abortion in the period 2009-2014. RESULTS: A history of induced abortion between 2009 and 2014 was reported by 17.4% of women (95% CI 16.0%, 18.9%); 28.7% (95% CI 26.9%, 30.6%) were currently using a method of contraception and 23.0% (95% CI 21.4%, 24.7%) were currently using a modern method of contraception. The majority (80.1%) of current contraceptive users were using a modern method. The adjusted analysis revealed no statistically significant association between a history of induced abortion and current contraceptive behaviour. Other factors were associated with modern contraceptive use. CONCLUSION: Overall, the use of contraception among sexually active women in Ghana was found to be low. Our findings showed that women's experience of induced abortion was unlikely to influence their current use of modern contraception.

Acceptability, adherence, and clinical outcomes, of amoxicillin dispersible tablets versus oral suspension in treatment of children aged 2-59 Months with pneumonia, Kenya: A cluster randomized controlled trial.

Amoxicillin dispersible tablet (DT) is now recommended by the WHO as a first-line drug for the treatment of pneumonia in children below 5 years. The study aim was to compare acceptability, adherence and clinical outcome of amoxicillin DT and amoxicillin oral suspension (OS) in the treatment of children aged 2-59 months with pneumonia in Kenya. We conducted a two-arm cluster randomized controlled trial and utilized quantitative methods. The community unit was the unit of randomization. Children aged 2-59 months with pneumonia were enrolled and treated with either amoxicillin DT or OS. Acceptability was defined as the perception of taste of medication as the same or better compared to other medicines and expression of willingness of caregivers to use DT/OS in future, adherence was measured based on the dose, frequency, and duration of treatment, and clinical outcome as complete resolution of symptoms without change of antibiotic treatment. Equivalence was defined as a difference of ≤8% between study arms. We found high levels of acceptability among both DT (93.9%) and OS (96.1%) arms (difference 2.3%, 90% CI -2.6-7.3). The objective measure of adherence on day four and the overall objective measure were significantly higher among children on DT compared to children on OS (88.7% vs. 41.5% (difference 47.2%, 90% CI 31.0-63.3) & 83.5% vs. 39% (difference 44.5%, 90% CI 27.9-60.9), respectively). Cure rates were high in both arms (DT (99.5%), OS (98.1%), difference 1.4%, 90% CI -0.2-3.2). There is reported better adherence to Amoxicillin DT compared to OS and equivalence in acceptability and clinical outcomes.

Inhibitors of apoptosis proteins (IAPs) are associated with T-2 toxin-induced decreased collagen II in mouse chondrocytes in vitro.

T-2 toxin is considered an unavoidable pollutant, which contaminates food crops and stockpiled cereals, impairing the health of humans and animals due to its multi-organ toxicity. Studies have shown that T-2 toxin can cause articular cartilage damage; however, the underlying molecular mechanism is still unclear. Here, we investigated the possible mechanism of the following inhibitors of apoptosis proteins (IAPs) family members: NAIP, cIAP1, cIAP2, XIAP, and Survivin, and their involvement in T-2 toxin-induced mouse chondrocyte damage. In this study, mouse articular chondrocytes were isolated and cultured in vitro, and the chondrocytes were then treated with 0, 5, 10, and 20 ng/mL T-2 toxin. Firstly, the toxic effect of T-2 toxin on chondrocytes was determined. CCK-8 assay results showed that T-2 toxin induced a dose-dependent inhibition of chondrocyte viability. Transmission electron microscopy demonstrated that T-2 toxin caused morphological changes in chondrocyte endoplasmic reticulum and an increase in mitochondrial swelling. In addition, Annexin-V-FITC/PI staining and caspase 3 protein expression showed that T-2 toxin induced an increase in the apoptotic rate of chondrocytes. Secondly, it was found that T-2 toxin cause decreased expression of cellular and secreted Collagen II. Finally, we examined the expression of NAIP, cIAP1, cIAP2, XIAP, and Survivin in chondrocytes in the presence of T-2 toxin and their relationship with decreased Collagen II. The decrease in Collagen II was negatively correlated with the expression of cIAP1, cIAP2 and positively correlated with NAIP and Survivin mRNA level. Survivin mRNA level had a positive correlation with Collagen II as shown by partial correlation analysis. This study revealed the new role of IAPs in chondrocyte injury and provides new insights and clues into the mechanism of T-2 toxin-induced chondrocyte damage.

The dose-time effects of fluoride on the expression and DNA methylation level of the promoter region of BMP-2 and BMP-7 in rats.

Skeletal fluorosis is a chronic metabolic bone disease caused by excessive exposed to fluoride. Recent studies have shown that fluoride causes abnormal bone metabolism through disrupting the expression of Bone Morphogenetic Proteins (BMPs). However, the relationship between fluoride and BMPs is not fully understood, and the mechanism of fluoride on BMPs expression is still unclear. This study investigated the dose-time effects of fluoride on BMP-2 and BMP-7 levels and DNA methylation status of the promoter regions of these two genes in peripheral blood of rats. Eighty Wistar male rats were randomly divided into four groups and treated for 1 month and 3 months with distilled water (control), 25 mg/L, 50 mg/L or 100 mg/L of sodium fluoride (NaF). Rats exposed to fluoride had higher protein expression of BMP-2 and BMP-7 in plasma at 1 month and 3 months. An increase in BMP-2 expression was also observed with an increase of fluoride exposure time. Significant hypomethylation was observed in 2 CpG sites (CpGs) of BMP-2 and 1 CpG site of BMP-7 promoter regions in the fluoride treatment groups. It concludes that fluoride has a dose-response effect on BMP-2 in fluorosis rats, and fluoride-induced hypomethylation of specific CpGs may play an essential role in the regulation of BMP-2 and BMP-7 expression in rats.