Protective effects of Vitamin C and E on fluorosis-induced gene expression in oxidative, apoptotic, and PI3K/AKT pathways in liver and kidney tissues

• Ahmet Cihat–Öner Van Yuzuncu Yıl University, Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology. Van, Türkiye. https://orcid.org/0000-0001-6614-4347
• Ayşe Usta Van Yuzuncu Yıl University, Faculty of Science, Department of Chemistry. Van, Türkiye. https://orcid.org/0000-0002-5522-3469
• Veysel Yüksek Van Yuzuncu Yıl University, Özalp Vocational School, Department of Medical Laboratory Technician. Van, Türkiye. https://orcid.org/0000-0001-7432-4989
• Sedat Çetin Ankara Yıldırım Beyazıt University, Department of Veterinary Medicine, Vocational School of Health Services. Ankara, Türkiye. https://orcid.org/0000-0002-6102-8571
• Semiha Dede Van Yuzuncu Yıl University, Faculty of Veterinary Medicine, Department of Biochemistry. Van, Türkiye. https://orcid.org/0000-0001-5744-6327
• Ayşegül Öner Van Yüzüncü Yıl University Institute of Health Sciences, Van, Türkiye. https://orcid.org/0000-0002-2906-3035

DOI: https://doi.org/10.52973/rcfcv-e363924

Keywords: Fluorosis, Antioxidants, Vitamin C, Vitamin E, Phosphoinositide 3–Kinase/Protein Kinase B pathway, Apoptosis, Oxidative stress, Gene expression

Abstract

This study aimed to investigate the modulatory effects of vitamin C and vitamin E on fluorosis-induced gene expression alterations in oxidative stress (Glutathione Peroxidase 1, Neutrophil Cytosolic Factor 1, Superoxide Dismutase 1), apoptosis (Caspase 3, Caspase 8, Caspase 9), and Phosphoinositide 3–Kinase/ Protein Kinase B/ Mechanistic Target of Rapamycin signaling pathways (Phosphoinositide 3–Kinase, Protein Kinase B, Receptor Tyrosine Kinase 2, mechanistic Target of Rapamycin, Tumor Protein p53) in rats. Forty-eight male Wistar Albino rats were randomLy allocated into six groups. Sodium Fluoride (150 mg·kg–1·day–1) was administered via drinking water for 16 weeks, followed by oral vitamin supplementation (C and E) for 4 weeks. mRNA expression levels were analyzed using RT-qPCR. Sodium Fluoride exposure increased Neutrophil Cytosolic Factor 1 expression in both kidney and liver tissues (P<0.001), while reducing Glutathione Peroxidase 1 and Glutathione Peroxidase 1 levels. Vitamin E, vitamin C, and their combination significantly suppressed Neutrophil Cytosolic Factor 1 expression (P<0.001), whereas the recovery of Glutathione Peroxidase 1 and Glutathione Peroxidase 1 was significant only in kidney tissues (P<0.05). Sodium Fluoride also markedly upregulated the apoptotic genes Caspase 3, Caspase 8, and Caspase 9 (P<0.05), and antioxidant treatments substantially attenuated these increases (P<0.0001). Furthermore, all Phosphoinositide 3–Kinase/Protein Kinase B pathway-related genes were strongly overexpressed following Sodium Fluoride administration (P<0.0001), and vitamin supplementation effectively reduced these elevations in both tissues (P<0.0001). Vitamin C and vitamin E, particularly in combination, exhibit substantial protective effects by restoring gene expression patterns toward homeostatic levels. This implies that a combination of antioxidant supplements may provide a promising therapeutic tool in combating fluorosis-induced cellular dysfunction.

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