Angwa Linet Musungu, Nyadanu Sylvester Dodzi, Kanyugo Anne Murugi, Adampah Timothy, Pereira Gavin
Department of Clinical Medicine, Kabarak University, Private Bag, 20157, Kabarak, Kenya.
Curtin School of Population Health, Curtin University, Perth, Kent Street, Bentley, Western Australia, 6102, Australia.
Heliyon. 2023 Jul 29;9(8):e18646. doi: 10.1016/j.heliyon.2023.e18646. eCollection 2023 Aug.
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 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 , 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 , p53, Bax, and down-regulating Bcl-2 with a concomitant up-regulation of the Bax/Bcl-2 ratio.
不同的研究表明，氟化物可诱导非骨骼组织中的细胞凋亡，然而，这些实验研究的证据仍存在争议。本荟萃分析旨在阐明实验动物非骨骼组织中氟化物诱导细胞凋亡的机制。通过在PubMed、Embase、Web of Science核心合集、Scopus中进行详尽的数据库检索以及纳入研究的参考文献，确定了测量细胞凋亡的原始研究。采用标准化均数差（SMD）的随机效应模型进行荟萃分析。使用希金斯统计量评估研究的异质性。分别使用SYRCLE偏倚风险工具和埃格检验评估偏倚风险和发表偏倚。与对照组相比，氟化物处理组的总凋亡细胞增加，Bax、Bax/Bcl-2比值、caspase-3、caspase-8、caspase-9、Cyt和p53的表达增加，Bcl-2的表达减少。然而，两组中APAF-1的表达没有差异的证据。亚组分析突出了干预期在改变氟化物凋亡效应中的作用，以及不同动物物种和组织的易感性和耐受性各不相同。荟萃回归分析表明，研究中总凋亡细胞的效应大小受动物物种影响，Bax的效应大小受样本来源影响。本荟萃分析的结果表明，氟化物通过上调caspase-3、-8和-9、Cyt、p53、Bax以及下调Bcl-2，并伴随Bax/Bcl-2比值的上调来诱导细胞凋亡。
