Modulation of the Nrf-2 and HO-1 signalling axis is associated with Betaine's abatement of fluoride-induced hepatorenal toxicities in rats.

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.