Sodium fluoride causes oxidative stress and apoptosis in the mouse liver

Abstract

The current study was conducted to investigate the effect of sodium fluoride (NaF) on the oxidative stress and apoptosis as well as their relationship in the mouse liver by using methods of flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), western blot, biochemistry and experimental pathology. 240 four-week-old ICR mice were randomly divided into 4 groups and exposed to different concentration of NaF (0 mg/kg, 12 mg/kg, 24 mg/kg and 48 mg/kg) for a period of 42 days. The results showed that NaF caused oxidative stress and apoptosis. NaF-caused oxidative stress was accompanied by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreasing mRNA expression levels and activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX) and glutathione-s-transferase (GST). NaF induced apoptosis via tumor necrosis factor recpter-1 (TNF-R1) signaling pathway, which was characterized by significantly increasing mRNA and protein expression levels of TNF-R1, Fas associated death domain (FADD), TNFR-associated death domain (TRADD), cysteine aspartate specific protease-8 (caspase-8) and cysteine aspartate specific protease-3 (caspase-3) in dose- and time-dependent manner. Oxidative stress is involved in the process of apoptotic occurrence, and can be triggered by promoting ROS production and reducing antioxidant function. NaF-caused oxidative stress and apoptosis finally impaired hepatic function, which was strongly supported by the histopathological lesions and increased serum alanine amino transferase (ALT), aspartic acid transferase (AST), alkaline phosphatase (AKP) activities and TBIL contents.

Potential toxicity of aluminum and fluoride on some biochemical aspects of male rat’s offspring

“…On the other hand, both ascorbic acid and GSH are among the most active reducing substances in living tissues that attenuate the reactive oxygen species. It is relevant to mention that the increased enzyme levels ALT and AST activity are considered as an indicator of liver damage and degeneration of the hepatic cells and thus alterations in liver function (Bouaziz et al, 2006;Bouaziz, Amaraa, Essefia, Croute, & Zeghal, 2010;Eraslan, Kanbur, & Silici, 2007;Hassan & Yousef, 2009;Kanbur, Eraslan, Silici, & Karabacak, 2009;Lu et al, 2017;Xiong et al, 2007;Zhou et al, 2015). With respect to the total protein level, either fluoride or aluminum concentration can lower the serum total protein level; on the other hand, Al might have interfered with the process of translation at a post-transcriptional level to inhibit the production of protein end products (Chatterjee, Mahapatra, & Sarkar, 2016;Chinoy & Memon, 2001;El-Demerdash, 2004;Michael, Barot, & Chinoy, 1996;Sallam, Nasser, Yousef, El-morsy, & Mahmoud, 2005;Yousef, 2005).…”

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

“…The liver samples (n = 8 per group, half male and female) were stored in liquid nitrogen and homogenized for RNA extraction. The method of RNA extraction was the same as that described by Lu and coworkers [25]. The total RNA of the liver samples was extracted using RNAiso Plus (9109; Takara, China).…”

“…Following the combination of ligands and receptors, FADD and TRADD adaptor proteins are being recruited, which then initiate the formation of deathinducing signaling molecules and further activate caspase-8 (a central mediator of the death receptor signaling pathway) [54]. The activated caspase-8 catalyzes the proteolysis of caspase-3 and drives the cascade reactions of downstream signaling molecules [25]. All the above findings clearly revealed that the TNF-R1 signaling pathway was involved in Cu-induced hepatic apoptosis.…”

“…It has been found that overexposure to Cu can result in mitochondrial dysfunction and increase the protein expression levels of cytosolic cytochrome (Cyt c) in the chicken liver [22], mouse brain [23], and chicken testis [24]. Besides, the death receptor pathway is also one of the main apoptosis signaling pathways [25], which belongs to the extrinsic apoptosis pathway. At the cell surface level, some of the well-characterized death receptors include Fas receptor and tumor necrosis factor receptor-1 (TNF-R1) that can bind to tumor necrosis factor alpha (TNF-α), a proinflammatory cytokine.…”

Pulsed Electromagnetic Fields Alleviates Hepatic Oxidative Stress and Lipids Accumulation in db/db mice

“…For its abundance, GSH serves as a cellular reductant and metabolic controller which is able to scavenge the free radicals against oxidative damage 27 . In order to achieve the purpose of counteract peroxide, the GSH-Px would promote the reaction between GSH and H 2 O 2 28 . And it could convert the GSH (reduced form of glutathione) as a co-substrate into GSSG (oxidized form of glutathione).…”