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

Niu, Qiang; Mu, Lati; Li, Shugang; Xu, Shangzhi; Ma, Ruling; Guo, Shuxia

doi:10.1007/s12011-015-0409-1

Cited by 20 publications

(14 citation statements)

References 28 publications

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“…In this study, fluoride may exert a certain impact on iron metabolism, cause iron accumulation in the liver of mouse, eventually leading to liver iron overload. This is supported by our previous in vitro study that fluoride induced iron overload accompanied by increased Hepcidin but decreased FPN expression (Niu et al, 2016). Similarly, Lee et al (2015) demonstrated that excessive iron induced hepcidin activation and FPN degradation in human liver SK-HEP-1 cells, thus resulting in reactive oxygen species (ROS) generation.…”

Section: Discussionsupporting

confidence: 67%

“…In iron overload patients or animals, accumulated iron facilitates the formation of free radical that disrupt the redox balance of the cells, thus causing oxidative stress (Toyokuni, 2011). Although previously we have confirmed that iron overload is involved in fluoride-induced oxidative injury in human embryo hepatocytes (Niu et al, 2016), the in vivo evidence of fluoride-induced oxidative stress resulting from iron overload is still obscure. The results of present study showed an increased total iron content in fluoride-treated mouse liver, suggestive of iron overload.…”

Section: Discussionmentioning

confidence: 84%

“…Recently, we have found that iron overload is implicated in fluoride-induced oxidative injury in human embryo hepatocytes, and that this iron overload associated oxidative stress can be rescued by a naturally occurring botanicals called grape seed proanthocyanidin extract (GSPE) (Niu et al, 2016), whose antioxidant capacity is closely related to its iron-chelating effects (Bagchi et al, 2014;Weber et al, 2007). However, the in vivo evidence of fluoride-induced iron overload correlated with oxidative stress and the protective effect of GSPE in the liver is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract

Niu

He²,

et al. 2018

J. Toxicol. Sci.

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-Emerging evidence has demonstrated that iron overload plays an important role in oxidative stress in the liver. This study aimed to explore whether fluoride-induced hepatic oxidative stress is associated with iron overload and whether grape seed proanthocyanidin extract (GSPE) alleviates oxidative stress by reducing iron overload. Forty Kunming male mice were randomly divided into 4 groups and treated for 5 weeks with distilled water (control), sodium fluoride (NaF) (100 mg/L), GSPE (400 mg/kg bw), or NaF (100 mg/L) + GSPE (400 mg/kg bw). Mice exposed to NaF showed typical poisoning changes of morphology, increased aspartate aminotransferase and alanine aminotransferase activities in the liver. NaF treatment also increased MDA accumulation, decreased GSH-Px, SOD and T-AOC levels in liver, indicative of oxidative stress. Intriguingly, all these detrimental effects were alleviated by GSPE. Further study revealed that NaF induced disorders of iron metabolism, as manifested by elevated iron level with increased hepcidin but decreased ferroportin expression, which contributed to hepatic oxidative stress. Importantly, the iron dysregulation induced by NaF could be normalized by GSPE. Collectively, these data provide a novel insight into mechanisms underlying fluorosis and highlight the potential of GSPE as a naturally occurring prophylactic treatment for fluoride-induced hepatotoxicity associated with iron overload.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

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Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract

Niu

He²,

et al. 2018

J. Toxicol. Sci.

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“…Kuppusamy and Tan (2011) anticipated a protective effect of deferoxamine against iron mediated oxidative stress along with iron chelator property. Additionally Niu et al (2016) reported that, Q prevents iron-induced oxidative damage in human hepatic cells and endocrinal gland by decreasing iron content and increasing antioxidants, including GPx, SOD, and total antioxidant capacity. David et al (2008) provided evidence that, combined treatment with DFO and Q is capable of decreasing oxidative load on neuronal cell in the striatum as evidenced by an increase in the total GSH and SOD levels.…”

Section: Discussionmentioning

confidence: 99%

The Role of Deferoxamine and Quercetin on The Short Term Chronic Toxicity of Iron on The Pituitary, Ovaries and Uterus of Prepubertal Albino Rats

Megahed

2020

Zagazig Journal of Forensic Medicine

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Iron is an important metal for Hypothalamic-pituitary-gonadal axis. Deferoxamine used as a potent antioxidant plus its chelating function. Quercetin is an effective antioxidant and also reported to have estrogenic activities. The aim of this study was to evaluate the role of deferoxamine and quercetin in the treatment of toxicity induced by short term chronic administration of iron in prepubertal female rats. One hundred and ten rats were divided into 5 groups: Group I : control (40 rats). Group II:(10 rats) injected IP daily with deferoxamine (DFO) (125mg /kg ) for 4 weeks. Group III:( 10 rats ) treated with quercetin (Q) (2g/kg daily) orally for 4 weeks. Group IV:( 10 rats ) received deferoxamine + quercetin for 4 weeks. Group V: (40 rats) subdivided into 4 sub-groups, Va: injected IP daily with Iron dextran (300 mg/kg) for 4 weeks then rats were sacrificed and submitted to biochemical and histopathological examination. Vb: injected intraperitoneally daily with iron dextran for 4 weeks, then received daily intraperitoneal deferoxamine for another 4 weeks. Vc: injected intraperitoneally daily with iron dextran for 4 weeks, then received daily quercetin orally by for another 4 weeks. Vd: injected intraperitoneally daily with iron dextran for 4 weeks, then received daily intraperitoneal deferoxamine + quercetin orally for another 4 weeks. The results showed significant increase in serum iron concentration, ferritin and NTBI and TBARS with significant decrease in serum (LH),(FSH) and estradiol hormones and serum (TAC) values in iron group when compared with other groups accompanied by histopathological changes in pituitary, ovaries and uterus, with marked iron deposits detected by Prussian blue stain and increased expression of caspase 3 . Treatment with deferoxamine or quercetin showed improvement in these parameters which nearly were equally effective. Combined treatment with deferoxamine and quercetin was better than single ones.

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“…Activation of Nrf2 can promote the expression of antioxidant genes and induce synthesis of phase II detoxifying enzymes [48]. Studies have shown that Nrf2 plays a crucial role in cellular resistance to oxidation and exogenous damage [49,50]. Recent studies have indicated that activating the Nrf2/ARE pathway has a hepato-protective effect [51,52].…”

Section: Discussionmentioning

confidence: 99%

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

et al. 2016

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Lead is harmful for human health and animals. Proanthocyanidins (PCs), a natural antioxidant, possess a broad spectrum of pharmacological and medicinal properties. However, its protective effects against lead-induced liver damage have not been clarified. This study was aimed to evaluate the protective effect of PCs on the hepatotoxicity of male Kunming mice induced by chronic lead exposure. A total of 70 healthy male Kunming mice were averagely divided into four groups: control group, i.e., the group exposed to lead, the group treated with PCs, and the group co-treated with lead and PCs. The mice exposed to lead were given water containing 0.2% lead acetate. Mice treated in the PCs and PCs lead co-treated groups were given PC (100 mg/kg) in 0.9% saline by oral gavage. Lead exposure caused a significant elevation in the liver function parameters, lead level, lipid peroxidation, and inhibition of antioxidant enzyme activities. The induction of oxidative stress and histological alterations in the liver were minimized by co-treatment with PCs. Meanwhile, the number of Transferase-Mediated Deoxyuridine Triphosphate-Biotin Nick End Labeling (TUNEL)-positive cells was significantly reduced in the PCs/lead co-treated group compared to the lead group. In addition, the lead group showed an increase in the expression level of Bax, while the expression of Bcl-2 was decreased. Furthermore, the lead group showed an increase in the expression level of endoplasmic reticulum (ER) stress-related genes and protein (GRP78 and CHOP). Co-treated with PCs significantly reversed these expressions in the liver. PCs were, therefore, demonstrated to have protective, antioxidant, and anti-ER stress and anti-apoptotic activities in liver damage caused by chronic lead exposure in the Kunming mouse. This may be due to the ability of PCs to enhance the ability of liver tissue to protect against oxidative stress via the Nrf2/ARE signaling pathway, resulting in decreasing ER stress and apoptosis of liver tissue.

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

Cited by 20 publications

References 28 publications

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract

Fluoride-induced iron overload contributes to hepatic oxidative damage in mouse and the protective role of Grape seed proanthocyanidin extract

The Role of Deferoxamine and Quercetin on The Short Term Chronic Toxicity of Iron on The Pituitary, Ovaries and Uterus of Prepubertal Albino Rats

Proanthocyanidins Attenuation of Chronic Lead-Induced Liver Oxidative Damage in Kunming Mice via the Nrf2/ARE Pathway

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