NaF 对体外人体血小板线粒体能量生成的抑制作用。

IF 3.6 Q2 TOXICOLOGY Frontiers in toxicology Pub Date : 2024-09-05 eCollection Date: 2024-01-01 DOI:10.3389/ftox.2024.1421184
Tetsuhiro Tsujino, Tomoni Kasahara, Hideo Kawabata, Taisuke Watanabe, Koji Nishiyama, Yutaka Kitamura, Takao Watanabe, Hajime Okudera, Tomoharu Mochizuki, Takashi Ushiki, Tomoyuki Kawase
{"title":"NaF 对体外人体血小板线粒体能量生成的抑制作用。","authors":"Tetsuhiro Tsujino, Tomoni Kasahara, Hideo Kawabata, Taisuke Watanabe, Koji Nishiyama, Yutaka Kitamura, Takao Watanabe, Hajime Okudera, Tomoharu Mochizuki, Takashi Ushiki, Tomoyuki Kawase","doi":"10.3389/ftox.2024.1421184","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability.</p><p><strong>Methods: </strong>Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction.</p><p><strong>Result: </strong>NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF.</p><p><strong>Conclusion: </strong>At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"6 ","pages":"1421184"},"PeriodicalIF":3.6000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410780/pdf/","citationCount":"0","resultStr":"{\"title\":\"Inhibitory effects of NaF on mitochondrial energy generation in human platelets <i>in vitro</i>.\",\"authors\":\"Tetsuhiro Tsujino, Tomoni Kasahara, Hideo Kawabata, Taisuke Watanabe, Koji Nishiyama, Yutaka Kitamura, Takao Watanabe, Hajime Okudera, Tomoharu Mochizuki, Takashi Ushiki, Tomoyuki Kawase\",\"doi\":\"10.3389/ftox.2024.1421184\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability.</p><p><strong>Methods: </strong>Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction.</p><p><strong>Result: </strong>NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF.</p><p><strong>Conclusion: </strong>At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP.</p>\",\"PeriodicalId\":73111,\"journal\":{\"name\":\"Frontiers in toxicology\",\"volume\":\"6 \",\"pages\":\"1421184\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11410780/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/ftox.2024.1421184\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/ftox.2024.1421184","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:氟是一种有益的离子,已被用于从工业产品到治疗等各个领域。然而,由于氟的治疗指数较窄,有时在人体内浓度相对较高时,氟会成为一种有毒物质。基于对遗传稳定性的关注,人们主要在有核、粘附的细胞(如成纤维细胞)中研究氟的细胞毒性作用。然而,人们对血细胞,尤其是无核血小板对氟化物的敏感性知之甚少。为了填补这一文献空白,我们研究了相对低浓度的氟对血小板能量代谢、功能和活力的影响:从 15 名非吸烟的健康男性(年龄:28-63 岁)中制备富血小板血浆(PRP),并在微管中用 NaF(0.5 或 1.0 mM)处理长达 3 天。根据聚集和粘附活动评估血小板功能。根据细胞内 ATP 水平、细胞外乳酸水平和呼吸活动评估血小板的能量代谢。使用细胞化学方法观察线粒体膜电位(Em)和活性氧(ROS)的定位。通过细胞计数和四唑还原法评估血小板活力:结果:NaF(1 mM)能明显降低血小板的活力并抑制其功能。在这些现象的背后,NaF 大大降低了线粒体 Em,增加了 ROS 的产生,同时显著降低了耗氧量和 ATP 水平。同时,NaF 还增加了乳酸水平。虽然没有统计学意义,但在 0.5 mM NaF 时也观察到了类似的影响:结论:在相对较低的水平下,NaF 有可能主要通过抑制线粒体能量生成来削弱血小板功能。细胞毒性可能与 ROS 的产生直接相关。这些研究结果表明,当局部使用 NaF 时,例如用于预防口腔龋齿,NaF 可能会干扰内源性和外源性血小板以 PRP 形式的伤口愈合和组织再生。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Inhibitory effects of NaF on mitochondrial energy generation in human platelets in vitro.

Background: fluoride is a beneficial ion that has been used in various fields, from industrial products to therapeutics. However, due to its narrow therapeutic index, fluoride sometimes acts as a toxic agent at relatively higher concentrations in the human body. Based on the interest in genetic stability, its cytotoxic effects have been investigated mainly in nucleated, adherent cells, such as fibroblasts. However, the sensitivity of blood cells, especially anucleate platelets, to fluoride is poorly understood. To fill this gap in the literature, we investigated the effects of relatively low levels of fluoride on platelet energy metabolism, function, and viability.

Methods: Platelet-rich plasma (PRP) was prepared from 15 non-smoking healthy male adults (age: 28-63) and treated with NaF (0.5 or 1.0 mM) in microtubes for up to 3 days. Platelet function was evaluated based on aggregation and adhesion activities. Platelet energy metabolism was evaluated based on intracellular ATP levels, extracellular lactate levels, and respiration activities. The mitochondrial membrane potential (Em) and localization of reactive oxygen species (ROS) were visualized using cytochemical methods. Platelet viability was evaluated by cell counting and tetrazolium reduction.

Result: NaF (1 mM) significantly reduced platelet viability and inhibited functions. Behind these phenomena, NaF substantially decreased mitochondrial Em and increased ROS production along with significant decreases in oxygen consumption and ATP levels. Simultaneously, NaF increased the lactate levels. Although not statistically significant, similar effects were observed at 0.5 mM NaF.

Conclusion: At relatively low levels, NaF has the potential to attenuate platelet function probably primarily through the inhibition of mitochondrial energy generation. Cytotoxicity may be directly related to ROS production. These findings suggest that when used topically, for example, for caries prevention in the oral cavity, NaF could interfere with wound healing and tissue regeneration by endogenous and exogenously added platelets in the form of PRP.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
3.80
自引率
0.00%
发文量
0
审稿时长
13 weeks
期刊最新文献
Considering future qualification for regulatory science in the early development of microphysiological systems: a case study of microthrombosis in a Vessel-on-Chip. Protective effects of Pelargonium graveolens (geranium) oil against cefotaxime-induced hepato-renal toxicity in rats. The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following in utero opioid exposures in mouse fetuses. In vitro toxicological evaluation of pouched portioned oral nicotine products. Heterogenous bioluminescence patterns, cell viability, and biofilm formation of Photobacterium leiognathi strains exposed to ground microplastics.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1