| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Rocha, JBT, et al.
(författare)
-
Mercury toxicity
- 2012
-
Ingår i: Journal of biomedicine & biotechnology. - : Hindawi Limited. - 1110-7251 .- 1110-7243. ; 2012, s. 831890-
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 5. |
- Aaseth, J, et al.
(författare)
-
Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer's Disease
- 2021
-
Ingår i: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:17
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present review is to discuss traditional hypotheses on the etiopathogenesis of Alzheimer’s disease (AD), as well as the role of metabolic-syndrome-related mechanisms in AD development with a special focus on advanced glycation end-products (AGEs) and their role in metal-induced neurodegeneration in AD. Persistent hyperglycemia along with oxidative stress results in increased protein glycation and formation of AGEs. The latter were shown to possess a wide spectrum of neurotoxic effects including increased Aβ generation and aggregation. In addition, AGE binding to receptor for AGE (RAGE) induces a variety of pathways contributing to neuroinflammation. The existing data also demonstrate that AGE toxicity seems to mediate the involvement of copper (Cu) and potentially other metals in AD pathogenesis. Specifically, Cu promotes AGE formation, AGE-Aβ cross-linking and up-regulation of RAGE expression. Moreover, Aβ glycation was shown to increase prooxidant effects of Cu through Fenton chemistry. Given the role of AGE and RAGE, as well as metal toxicity in AD pathogenesis, it is proposed that metal chelation and/or incretins may slow down oxidative damage. In addition, selenium (Se) compounds seem to attenuate the intracellular toxicity of the deranged tau and Aβ, as well as inhibiting AGE accumulation and metal-induced neurotoxicity.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Branco, V, et al.
(författare)
-
N-Acetylcysteine or Sodium Selenite Prevent the p38-Mediated Production of Proinflammatory Cytokines by Microglia during Exposure to Mercury (II)
- 2022
-
Ingår i: Toxics. - : MDPI AG. - 2305-6304. ; 10:8
-
Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is known for its neurotoxicity and is reported to activate microglia cells at low exposure levels. Since mercury decreases the activity of the glutathione and thioredoxin systems, we hypothesize that Hg would, in turn, disrupt microglia homeostasis by interfering with redox regulation of signaling pathways. Thus, in this work, we analyzed the effect of exposure to Hg2+ on nuclear translocation and activation of NF-kB (p50) and p38 and pro-inflammatory gene transcription (IL-1ß; iNOS, TNF-alpha) considering the interaction of Hg with the glutathione system and thioredoxin systems in microglial cells. N9 (mouse) microglia cells were exposed to different concentrations of Hg2+ and the 24 h EC50 for a reduction in viability was 42.1 ± 3.7 μM. Subsequent experiments showed that at sub-cytotoxic levels of Hg2+, there was a general increase in ROS (≈40%) accompanied by a significant depletion (60–90%) of glutathione (GSH) and thioredoxin reductase (TrxR) activity. Upon 6 h of exposure to Hg2+, p38 (but not p50) accumulated in the nucleus (50% higher than in control), which was accompanied by an increase in its phosphorylation. Transcript levels of both IL1-ß and iNOS were increased over two-fold relative to the control. Furthermore, pre-exposure of cells to the p38 inhibitor SB 239063 hindered the activation of cytokine transcription by Hg2+. These results show that disruption of redox systems by Hg2+ prompts the activation of p38 leading to transcription of pro-inflammatory genes in microglia cells. Treatment of N9 cells with NAC or sodium selenite—which caused an increase in basal GSH and TrxR levels, respectively, prevented the activation of p38 and the transcription of pro-inflammatory cytokines. This result demonstrates the importance of an adequate nutritional status to minimize the toxicity resulting from Hg exposure in human populations at risk.
|
|
