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Antioxidants against oxidative stress induced by sodium fluoride toxicity in murine models: A systematic review.
| Journal of Trace Elements in Medicine and Biology | Ortiz-Barroso G, Ramírez-Orozco RE, Esparza-Villalpando V, Macedo-Mendoza M, Barrios-García T, Pulido-Hornedo NA. | 88:127619.
Antioxidants Mitigating F toxicity Oxidative Stress Review

Abstract

Introduction

Fluorosis, a condition resulting from excessive fluoride intake, leads to dental, skeletal, and soft tissue alterations through mechanisms that induce oxidative stress. With its potential to significantly impact the field, this review aims to assess the efficacy of antioxidant agents in murine models exhibiting fluorosis-induced toxicity. By transferring electrons to oxidizing agents, antioxidants can attenuate oxidation reactions and mitigate cellular damage.

Methodology

This systematic review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, encompassing articles investigating the impact of antioxidant substances on murine fluorosis models, explicitly focusing on oxidative stress markers and antioxidant levels across various tissues.

Results

A qualitative synthesis of 79 articles highlights antioxidant agents such as vitamin C, vitamin E, selenium, carotenoids, polyphenolic compounds (including flavonoids and polyphenolic acids), amino acids, and others among animals with fluorosis induction showed variations in oxidative stress markers and antioxidant activity levels under different administration protocols compared to those receiving prophylactic, concomitant concurrent, or therapeutic antioxidant treatments.

Conclusion

Fluoride administration across diverse doses and durations elicits heightened oxidative stress markers in multiple rodent tissues. The current evidence suggests that some antioxidants are effective as a prophylactic and concurrent in murine models of fluorosis. However, the methodological differences between studies prevent the establishment of a protocol for potential standardized use.

Graphical Abstracthttps://ars.els-cdn.com/content/image/1-s2.0-S0946672X2500032X-ga1_lrg.jpg

EXCERPTS:

Introduction

Fluorine is an element with physiological functions; it is found as fluorides forming bonds with other elements naturally in foods and groundwater and added to some products; however, excessive consumption of fluorides causes a toxicity called fluorosis. Fluorosis has become a public health problem worldwide in areas where high fluoride (F) content in groundwater is reported, exceeding 1.5 mg/L of fluorides, which are the levels that the World Health Organization (WHO) [1], [2], [3] The concentrations determine the damage caused, the route of exposure, and the environment surrounding the cell. The alterations and manifestations that occur will depend on the damaged tissue. Based on that, fluorosis will be classified as dental, skeletal, and non-skeletal. When toxicity occurs in soft tissues, it is classified as non-skeletal fluorosis [3].

Complete knowledge of how fluorosis triggers oxidative stress is required. However, it is generally attributed to organelle disruption, altered pH, electrolyte imbalance, and inhibition of proteins; the latter is what most papers attribute to the primary mechanism of toxicity [4]. F has demonstrated the ability to reduce the antioxidant enzymes activity and other molecules, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and glutathione S-transferase (GST), which in turn led to increased levels of reactive oxygen species (ROS) and malondialdehyde (MDA) levels. This alteration has been reported in animal models in various tissues such as the liver, kidney, spleen, brain, heart, and testes [5], [6], [7], [8], [9], [10]. The alterations caused by fluorosis result in oxidative stress, which is reflected depending on the system that is being damaged [3], [4], [11].

Antioxidants are a class of chemical substances that can transfer electrons to an oxidizing agent, such as ROS, inhibiting oxidation reactions and preventing cellular damage (Fig. 1). Enzymatic (SOD, CAT, GPx) and non-enzymatic (GSH) antioxidant defense systems control cellular redox balance in the body under normal conditions. SOD plays a role in the conversion of superoxide anion radical to H2O2, and CAT and GPx play a role in the dissociation of H2O2 into H2O and O2. GSH, abundant in cells, plays an important role in oxidative stress by directly reacting with electrofilms or as a cofactor. GSH also regulates the redox status of specific thiol residues of proteins, such as caspases, stress kinases, and transcriptional factors [12], [13], [14], [15], [16]. The wide diversity of antioxidant agents, dosages, timing, and routes of administration make it complex and clinically impractical to directly assess their protective effect in mitigating the harmful consequences of fluorosis. Hence, this review aims to report the effectiveness of antioxidant agents under murine models of fluorosis toxicity.

ABSTRACT ONLINE AT https://www.sciencedirect.com/science/article/abs/pii/S0946672X2500032X?via%3Dihub