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ORIGINAL RESEARCH article
Front. Toxicol.
Sec. In Vitro Toxicology
Volume 6 - 2024 |
doi: 10.3389/ftox.2024.1421184
This article is part of the Research Topic Unravelling the Health Impacts of Toxic Exposures View all articles
Inhibitory effects of NaF on mitochondrial energy generation in human platelets in vitro
Provisionally accepted- 1 Tokyo Plastic Dental Society, Tokyo, Japan
- 2 Niigata University, Niigata, Japan
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.
Keywords: Fluoride, platelets, Aggregation, Adhesion, Respiration, ATP
Received: 22 Apr 2024; Accepted: 22 Aug 2024.
Copyright: © 2024 Tsujino, Kasahara, Kawabata, Watanabe, Nishiyama, Kitamura, Watanabe, Okudera, Mochizuki, Ushiki and KAWASE. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
TOMOYUKI KAWASE, Niigata University, Niigata, Japan
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