Modulation of the Nrf-2 and HO-1 signalling axis is associated with Betaine's abatement of fluoride-induced hepatorenal toxicities in rats.
Naunyn Schmiedebergs Arch Pharmacol
; 397(10): 7725-7745, 2024 10.
Article
em En
| MEDLINE
| ID: mdl-38713257
ABSTRACT
Sodium fluoride (NaF) ingestion has several detrimental effects in humans and rodents. NaF mechanisms of toxicity include perturbation of intracellular redox homeostasis and apoptosis. Betaine (BET) is a modified amino acid with anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigates BET's effect on NaF-induced hepatorenal toxicities in rats. Experimental rats (n = 30) were randomly assigned to groups (n = 6) and treated by gavage for 28 days. Group I (2 mL of distilled water), Group II (NaF 9 mg/kg) alone, Group III (BET 100 mg/kg), Group IV (NaF 9 mg/kg and BET 1 50 mg/kg), and Group V (NaF 9 mg/kg and BET 2 100 mg/kg). Our findings revealed significantly (p < 0.05) increased hepatic transaminase activities alongside creatinine and urea levels following NaF-alone treatment in addition to increased oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, decreased superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, glutathione, and total sulfhydryl groups. The reduced levels of nuclear factor erythroid 2-related factor-2 and the activities of heme oxygenase-1, thioredoxin, and thioredoxin reductase in NaF-alone treated rats equally compromised cellular molecular responses to oxidative stress. Also, NaF increased (p < 0.05) hepatorenal inflammatory biomarkers-nitric oxide, interleukin-10, myeloperoxidase, and xanthine oxidase. Furthermore, caspase-3 and caspase-9 were increased (p < 0.05) in rats treated with NaF alone. Contrastingly, BET was observed to alleviate the harmful effects of NaF. Treatment with BET mitigated NaF-induced oxido-inflammatory responses and apoptosis in the experimental rat's hepatorenal system. The study demonstrates the potential of BET to abate NaF-induced hepatorenal toxicity.
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MEDLINE
Assunto principal:
Fluoreto de Sódio
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Betaína
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Transdução de Sinais
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Ratos Wistar
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Estresse Oxidativo
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Fator 2 Relacionado a NF-E2
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article