Mohammad Mehdi Ommati

Fluoride (F^-) exerts a dual role in agricultural systems, supporting dental mineralization at low levels but inducing multiorgan toxicity under chronic exposure. While the detrimental effects of F^- have been well documented, its interactions with co-occurring micronutrients (e.g., Zn, Se, I) and toxicants (e.g., Al, Cd, As) remain incompletely characterized in the context of food production and animal husbandry. Accumulating evidence indicates that essential micronutrients can attenuate F^- toxicity by potentiating antioxidant defenses and stabilizing metalloenzyme activity, whereas toxicants aggravate F^--mediated injury through synergistic oxidative damage. These multielement interactions modulate F^- bioavailability, tissue distribution, and organ-specific pathology in livestock tissues and food commodities. Critical knowledge gaps persist regarding cumulative exposure thresholds and the practical relevance of animal models for food safety risk assessment. This review synthesizes mechanistic insights into F^--element interactions and discusses emerging mitigation strategies to prevent or ameliorate fluorosis under real-world multicontaminant scenarios in agricultural settings.

Our previous studies have demonstrated that fluoride (F) overexposure is a risk factor for colonic microenvironment, yet its underlying mechanisms and the influencing factors remain poorly understood. Here, a rat model of F exposure (0, 25, 50, 100 mg/L in drinking water) combined with ovariectomy (OVX)-induced estrogen deficiency was established to investigate the roles of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in F-induced colonic damage under the state of estrogen deficiency. Result showed that F exposure significantly reduced occludin and claudin-1 expression, further resulting in the colon’s morphology impairment. Concurrently, F suppressed epithelial proliferation, decreased goblet cell numbers, and diminished short-chain fatty acid (SCFA) production. OVX-induced estrogen deficiency exacerbated F-induced colonic barrier damage and SCFA decreased. Mechanistically, estrogen deficiency aggravated F intestinal toxicity by further inhibiting the protein expression of Nrf2 and HO-1 and upregulating Keap1 protein expression, following downregulated Bcl-2 mRNA levels and upregulated Bax and caspase-3 mRNA levels, and promoting colonic epithelial cell apoptosis. These findings identify that Nrf2/HO-1 key protein disorders are involved in F-induced colonic barrier injury, and estrogen deficiency further aggravated F intestinal toxicity.

Chronic fluoride (F) exposure is linked to gonadotoxicity in females, yet the underlying molecular mechanisms remain unclear. This study investigated fluoride-induced reprotoxicity using advanced genomic profiling. RNA-seq analysis identified significant activation of autophagy, apoptosis, and IL-17 signaling pathways in fluoride-exposed female mice. To explore these mechanisms, F0 pregnant mice were exposed to deionized water (control) or 100 mg/L sodium fluoride (NaF) during gestation and throughout the F1 generation (n = 16 females/group), covering puberty to weaning and maturity. NaF exposure caused significant reductions in body weight, organ coefficients, and pathological indices, with increased ovarian autophagic vacuoles, mitochondrial injuries, and elevated serum/ovary LPS levels in F1 females. qRT-PCR, fluorescent staining, biochemical assays, and Western blotting confirmed the activation of IL-17 signaling, apoptosis, and autophagy. Moreover, 16S rRNA sequencing revealed gut microbiota dysbiosis in NaF-exposed F1 females, potentially exacerbating ovary injury via serum LPS elevation. The gut dysbiosis could justify deteriorated serum LPS levels and its connection to F-induced ovary injury. These findings provide mechanistic insights into fluoride-induced reprotoxicity, emphasizing the interplay of IL-17 signaling, autophagy, and apoptosis in disrupting cellular homeostasis and suggesting potential therapeutic targets.

Background: Taurine (TAU) is the most abundant non‐protein amino acid in the central nervous system (CNS). However, the molecular mechanism of TAU in the CNS is still poorly understood. Meanwhile, disruption in mitochondrial dynamics is evident in CNS disorders. This study aimed to investigate the effect of TAU on mitochondrial dynamics.Methods: TAU (0.25, 0.5 and 1% in drinking water) was administered to young mice for six months. Several memory/cognition parameters and indices of anxiety/depression were assessed. Meanwhile, various mitochondrial indices and the expression/activity of genes involved in mitochondrial biogenesis and dynamics (Akt, CREB, NRF1, TFAM, PGC‐1α, Mfn1, Mfn2, UCP2, PINK1, OPA1, Drp1 and Fis1) were examined.Results: TAU significantly enhanced memory performance, suppressed anxiety and depression‐like behaviour, increased mitochondrial biogenesis/dynamics and improved mitochondrial indices. It should be mentioned that there was no significant difference between different concentrations of TAU in changing most brain mitochondrial dynamic biomarkers in the current study.Conclusions: These findings offer more insights into the molecular mechanism for TAU's action in the CNS. However, there is a need for further research to confirm these effects in humans. Overall, this study suggests the potential application of TAU in various neurological disorders and the need for clinical studies on the effects of this amino acid in the brain.