A possible new mechanism and drug intervention for kidney damage due to arsenic poisoning in rats

Xu, Yancheng; Zeng, Qibing; Yao, Maolin; Yu, Chun; Zhang, Aihua

doi:10.1039/c5tx00165j

Cited by 19 publications

(30 citation statements)

References 17 publications

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“…In a pro-inflammatory environment, Treg cells release IL-17A; in the absence of inflammation, TGF-β promotes Treg differentiation to maintain immune tolerance [62,63]. Thus, in considering the effect of Gingko biloba treatment on the immune suppression and kidney damage in arsenic poisoned rats [29] and the results of this study, we conclude that GBE has a role in the balance of the Th17/Treg axis and shifts this balance to produce an anti-inflammatory effect. For arsenicosis patients, their inflammatory imbalance can be modified to restore immune homeostasis, thereby improving their immune function.…”

Section: Discussionmentioning

confidence: 63%

“…Gingko biloba has been used to enhance immune function in arsenic-poisoned rats and to relieve kidney damage [29]. We followed up 74 arsenicosis patients who received a course of 3-month placebo or GBE therapy.…”

Section: Gbe Attenuates Arsenicosis-induced Disruption Of the Th17/trmentioning

confidence: 99%

“…Dietary supplementation with GBE enhances the immune organ index and the number of T lymphocytes and adjusts the balance of T lymphocyte subsets, thereby enhancing immune function [27,28]. In rats with arsenic poisoning caused by coal-burning, Ginkgo biloba diminishes kidney damage and improves immune function [29]. Nevertheless, the specific role and mechanism of GBE against immune damage caused by arsenic are poorly understood, especially for populations exposed to arsenic.…”

Section: Introductionmentioning

confidence: 99%

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Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients

Xia¹,

Sun²,

Zou³

et al. 2020

Int. J. Biol. Sci.

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Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of Ginkgo biloba extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro-and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro-and anti-inflammatory T cell balance.

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Section: Discussionmentioning

confidence: 63%

Section: Gbe Attenuates Arsenicosis-induced Disruption Of the Th17/trmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients

Xia¹,

Sun²,

Zou³

et al. 2020

Int. J. Biol. Sci.

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show abstract

“…1 It is well-known that the kidney is the main organ of the urinary system that is primarily responsible for arsenic excretion; as such, its structure and function are vulnerable to damage. Renal dysfunction caused by arsenic has been demonstrated with epidemiologic investigations 11,12 as well as in animal studies, 13,14 mainly affecting the function of proximal convoluted tubules and glomeruli. Recent studies 9,15 in Taiwan have also revealed the relationship between arsenic exposure and chronic arsenic disease.…”

Section: Introductionmentioning

confidence: 98%

miR-191 is involved in renal dysfunction in arsenic-exposed populations by regulating inflammatory response caused by arsenic from burning arsenic-contaminated coal

Zou

Liu

et al. 2019

Hum Exp Toxicol

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Chronic exposure to arsenic may result in the manifestation of damage in multiple organs or systems of the body. Arsenic-induced renal dysfunction has been determined, but their pathogenesis has not been fully examined. In this study, we measured the expression levels of miR-191 in plasma, the contents of pro-inflammatory (interleukin (IL)-6 and tumor necrosis factor alpha) and anti-inflammatory (IL-2 and transforming growth factor beta) cytokines, and renal dysfunction indicators (blood urea nitrogen, blood creatinine, uric acid, and cystatin C) in serum from control and arsenic poisoning populations and analyzed the relationship between the miR-191, cytokines, and renal dysfunction indicators. The results clearly show the alteration of miR-191 expression was significantly associated with arsenic-induced renal dysfunction. Overall, the association of miR-191, inflammatory response and renal dysfunction, is clearly supported by the current findings. In other words, miR-191 is involved in renal dysfunction in exposed populations by regulating inflammatory response caused by coal-burning arsenic. The study provides a scientific basis for further studies of the causes of the arsenic-induced renal dysfunction, the biological role of miR-191, and targeted prevention strategies.

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“…8 Moreover, a large number of animal experiments and epidemiological data demonstrate that chronic exposure to arsenic can damage the immune system and ultimately lead to immune dysfunction. 9 –12…”

Section: Introductionmentioning

confidence: 99%

Arsenite induces dysfunction of regulatory T cells through acetylation control of the Foxp3 promoter

et al. 2020

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Arsenic is known to cause damage to the body’s immune system by inducing epigenetic changes. However, the molecular mechanism of this damage remains elusive. Here, we report that arsenic disrupts the morphology of lymphocytes, decreases cell viability, and results in abnormal proportions of T lymphocyte subsets. Moreover, our results revealed that arsenic can reduce global acetylation of histone H4 at K16 (H4K16 ac) in lymphocytes via decreasing the level of males absent on the first but upregulates mRNA and protein levels of the forkhead/winged-helix box P3 ( Foxp3) gene by increasing the acetylation of histone H4 at K16 (H4K16) at the promoter of Foxp3. Finally, arsenic-induced dysfunction of regulatory T cells (Tregs) could be ameliorated by trichostatin A. Our research indicates that arsenic-induced immunosuppressive effect in human lymphocytes may be related to the acetylation of H4K16 at the promoter of Foxp3 and that histone deacetylase inhibitors may play a role in the prevention and treatment of immune injury caused by arsenic.

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A possible new mechanism and drug intervention for kidney damage due to arsenic poisoning in rats

Cited by 19 publications

References 17 publications

Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients

Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients

miR-191 is involved in renal dysfunction in arsenic-exposed populations by regulating inflammatory response caused by arsenic from burning arsenic-contaminated coal

Arsenite induces dysfunction of regulatory T cells through acetylation control of the Foxp3 promoter

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