Activation of the AGE/RAGE system in the brains of rats and in SH-SY5Y cells exposed to high level of fluoride might connect to oxidative stress

Zhang, Kailin; Lou, Didong; Guan, Zhi‐Zhong

doi:10.1016/j.ntt.2015.01.007

Cited by 43 publications

(31 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analyses carried out so far show that one of the mechanisms by which fluorine influences the disorders in brain functioning is the increase of the synthesis of ROS and the weakening of the defensive mechanisms against their activity (the decrease in the activity of antioxidative enzymes) [43]. In the central nervous system, the intensity of the processes that utilize oxygen is very high.…”

Section: Introductionmentioning

confidence: 99%

“…Their intensive degradation ensues when they begin to differentiate. The increase in the synthesis and the concentration of AGEs in the organism is observed in pathological states [43, 50]. In properly functioning organisms, AGEs are quickly degraded in proteasomes.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there are five known types of receptors that bind the products of non-enzymatic glycation: MSR-1 (macrophage scavenger receptor), AGE-R1, AGE-R2 (which binds phosphoproteins), AGE-R3 (which recognizes galactosidic groups) and RAGE (the receptor for AGEs). While the receptors AGE-R1–3 and MSR-1 take part in the removal of the products of glycation from circulation, RAGE acts as a signal receptor activating the processes connected with the synthesis of ROS, transcription factors and the proinflammatory particles such as nuclear factor kB (NF-kB) and the previously mentioned MAP kinases (MAPK) [43, 50, 51]. RAGE demonstrates expression on macrophages, T lymphocytes, cardiomyocytes, endothelial cells, smooth muscle cells, neurons and dendritic cells [52].…”

Section: Introductionmentioning

confidence: 99%

“…The accumulation of AGEs in neurons increases the synthesis of ROS, disturbs the transmission of nervous impulses and stimulates the atrophy of nerve fibres. Moreover, it correlates with the increased expression of proteins that regulate the apoptosis and differentiation of cells [43, 53]. …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Dec

Łukomska

Maciejewska

et al. 2016

Biol Trace Elem Res

124

View full text Add to dashboard Cite

Fluorides occur naturally in the environment, the daily exposure of human organism to fluorine mainly depends on the intake of this element with drinking water and it is connected with the geographical region. In some countries, we can observe the endemic fluorosis—the damage of hard and soft tissues caused by the excessive intake of fluorine. Recent studies showed that fluorine is toxic to the central nervous system (CNS). There are several known mechanisms which lead to structural brain damage caused by the excessive intake of fluorine. This element is able to cross the blood-brain barrier, and it accumulates in neurons affecting cytological changes, cell activity and ion transport (e.g. chlorine transport). Additionally, fluorine changes the concentration of non-enzymatic advanced glycation end products (AGEs), the metabolism of neurotransmitters (influencing mainly glutamatergic neurotransmission) and the energy metabolism of neurons by the impaired glucose transporter—GLUT1. It can also change activity and lead to dysfunction of important proteins which are part of the respiratory chain. Fluorine also affects oxidative stress, glial activation and inflammation in the CNS which leads to neurodegeneration. All of those changes lead to abnormal cell differentiation and the activation of apoptosis through the changes in the expression of neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and MAP kinases. Excessive exposure to this element can cause harmful effects such as permanent damage of all brain structures, impaired learning ability, memory dysfunction and behavioural problems. This paper provides an overview of the fluoride neurotoxicity in juveniles and adults.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Dec

Łukomska

Maciejewska

et al. 2016

Biol Trace Elem Res

124

View full text Add to dashboard Cite

show abstract

“…Fluorosis can cause damage not only to skeletal tissue and teeth but also to soft tissues, such as the brain, liver, kidney, and spinal cord. Previous studies revealed that continuous intake of excessive fluoride may cause liver oxidative damage [2,3]. Some researchers believe that fluorine can directly attack antioxidant enzymes, weakening their activities and increasing free radical abundance [4].…”

Section: Introductionmentioning

confidence: 99%

Proanthocyanidin Protects Human Embryo Hepatocytes from Fluoride-Induced Oxidative Stress by Regulating Iron Metabolism

Niu

et al. 2015

Biol Trace Elem Res

View full text Add to dashboard Cite

To investigate whether grape seed proanthocyanidin extract (GSPE) antagonizes fluoride-induced oxidative injury by regulating iron metabolism, human embryo hepatic cells (L-02) were incubated with sodium fluoride (NaF, 80 mg/L) and/or GSPE (100 μmol/L) for 24 h. Results showed the glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and total antioxidant capacity (T-AOC) level of the NaF group were significantly lower than that of the control group (P < 0.05), while malondialdehyde (MDA) content increased in the NaF group compared with the control group (P < 0.05). Moreover, the indexes mentioned above showed opposite changes in the NaF + GSPE group. In addition, iron content significantly increased in the NaF group compared to the control group(P < 0.05) and significantly decreased in the NaF + GSPE group compared to the NaF group (P < 0.05). Furthermore, hepcidin (coded by HAMP) messenger RNA (mRNA) expression significantly increased in the NaF group compared to the control group(P < 0.05) and significantly decreased in the NaF + GSPE group compared to the NaF group (P < 0.05). Ferroportin 1 (coded by FPN1) mRNA expression significantly decreased in the NaF group compared to the control group (P < 0.05) and significantly increased in the NaF + GSPE group compared to the NaF group (P < 0.05). These results indicate that GSPE provides significant cellular protection against oxidative stress induced by excessive fluoride via the iron metabolism regulation.

show abstract

Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH‐SY5Y cells

Tang

Lai

Luo

et al. 2021

J Biochem & Molecular Tox

View full text Add to dashboard Cite

Previous studies both invivo and in vitro have revealed that high levels of fluoride cause neurotoxicity. Mangiferin has been reported to possess antioxidant, antiapoptotic, and anti‐inflammatory properties. The present study was designed to characterize the mechanisms by which mangiferin protects against NaF‐induced neurotoxicity. Increased levels of proapoptotic Bax, Caspase‐3, Caspase‐9, and cleaved‐caspase 3, as well as a decreased level of antiapoptotic Bcl‐2 induced by fluoride in human neuroblastoma SH‐SY5Y cells, these effects were prevented by pretreatment of mangiferin. In addition, mangiferin attenuated the enhancement of p‐JNK, reductions of Nrf2 and HO‐1, and increased level of the mitochondrial fission proteins Drp1 caused by fluoride. Moreover, oxidative stress, as reflected in the levels of reactive oxygen species, 8‐hydroxy‐2'‐deoxyguanosine, and 4‐hydroxynonenal, was elevated by fluoride and these effects were again ameliorated by mangiferin. In conclusion, protection by mangiferin against fluoride‐induced neurotoxicity involves normalizing the impaired mitochondrial apoptotic pathway and dynamics and reducing oxidative stress via inactivation of the JNK and activation of the Nrf2/HO‐1 pathways.

show abstract

Activation of the AGE/RAGE system in the brains of rats and in SH-SY5Y cells exposed to high level of fluoride might connect to oxidative stress

Cited by 43 publications

References 51 publications

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Proanthocyanidin Protects Human Embryo Hepatocytes from Fluoride-Induced Oxidative Stress by Regulating Iron Metabolism

Mangiferin prevents the impairment of mitochondrial dynamics and an increase in oxidative stress caused by excessive fluoride in SH‐SY5Y cells

Contact Info

Product

Resources

About