Broccoli has protective effects against oxidant-induced strand breaks~!

"broccoli intake was associated with increased protection against H(2)O(2)-induced DNA strand breaks and lower levels of oxidised DNA bases in PBMCs from smokers. This protective effect could be related to an overall improved antioxidant status."

Read more: CiteULike: DNA damage and repair activity after broccoli intake in young healthy smokers.:

Dysfunction of Glutathione S-Transferase Leads to Excess 4-Hydroxy-2-Nonenal and H2O2 and Impaired Cytokine Pattern in Cultured Keratinocytes and Blood of Vitiligo Patients

Dysfunction of Glutathione S-Transferase Leads to Excess 4-Hydroxy-2-Nonenal and H2O2 and Impaired Cytokine Pattern in Cultured Keratinocytes and Blood of Vitiligo Patients

Differences in Gene and Cell Behavior in Radical-Induced Oxidative Stress

This study offers a novel and detailed insight in the similarities and differences of the time-dependent oxidative stress responses induced by the oxidants H2O2 and menadione and show that these can be discriminated regarding their modulation of particular colon carcinogenesis-related mechanisms.

CiteULike: Global Gene Expression Analysis Reveals Differences in Cellular Responses to Hydroxyl- and Superoxide Anion Radical-Induced Oxidative Stress in Caco-2 Cells: "Briede, J. J., van Delft, J. M. H., de Kok, T. M. C. M., van Herwijnen, M. H. M., Maas, L. M., Gottschalk, R. W. H., and Kleinjans, J. C. S. (2010). Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol. Sci., 114(2):193-203."

Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling

Summary: Prxs function as redox sensors that transmit signals as part of the cellular response to oxidative stress. In mammals, Prx 3 and Prx 5 are targeted to the mitochondrial matrix. Mitochondria are a major source of hydrogen peroxide, and this oxidant is implicated in the damage associated with aging and a number of pathologies

Cox, A. G., Winterbourn, C. C., and Hampton, M. B. (2010). Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling. The Biochemical journal, 425(2):313-325. http://www.citeulike.org/user/HEIRS/article/6440040





Mitochondria and Free Radicals in Neurodegenerative Diseases

Polychlorinated biphenyl (pcb)-induced oxidative stress and cytotoxicity can be mitigated by antioxidants following exposure.

Title: Polychlorinated biphenyl (pcb)-induced oxidative stress and cytotoxicity can be mitigated by antioxidants following exposure.

Summary: "exposure of exponentially growing human breast and prostate epithelial cells to PCBs causes increased steady-state levels of intracellular O(2)(-) and H(2)O(2), induction of MnSOD or CuZnSOD activities, as well as clonogenic cell killing that could be inhibited by a clinically relevant thiol antioxidant, NAC, as well as by catalase and superoxide dismutase following PCB exposure."

Zhu, Y., Kalen, A. L., Li, L., Lehmler, H.-J. J., Robertson, L. W., Goswami, P. C., Spitz, D. R., and Aykin-Burns, N. (2009). Polychlorinated biphenyl (pcb)-induced oxidative stress and cytotoxicity can be mitigated by antioxidants following exposure. Free radical biology & medicine. http://www.citeulike.org/group/7833/article/5872908

Endogenous Peptide Protects Against Toxicants By Upregulating Nrf2/HO-1

Recent studies have shown that a peptide produced from thyroptropin-releasing hormone (TRH) in the hypothalamus called cyclo (His-Pro) (CHP) can provide neuroprotective effects against a number of toxicants including Paraquat, rotenone, glutamate and B-amyloid. The author determined that these effects are generated through the activation of Nrf2 and that the protective effects against Paraquat also involve HO-1. Knock-down of Nrf2 abolished these protective effects. Generally, the studies show evidence that CHP improves glutathione synthesis and prevented depletion and reduces the generation of ROS from these toxicants. Specifically, he notes that CHP is protective against H2O2 mediated apoptotic cell death. (Minelli) Paraquat exposure has been implicated as a risk factor for Parkinson's disease and having adverse effects on dopamine systems.

Other studies have shown that dopamine transmission is regulated by H2O2 and that H2O2 generated from respiring mitochondria are the major source of H2O2 neuronal signals. As we have noted, toxicants and other factors can lead to mitochondrial dysfunction which has been implicated in a number of health conditions including those commonly known as environmental illness. In the striatum, H2O2 controls dopamine release and it has been found that H2O2 inhibits dopamine release and activity through the activation of KATP channels.

Notes:

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  CHP is a substrate for OCT2 according to Taubert. Jonker explains that knock-down of OCT1 and OCT2 in the kidney can lead to an inhibition of excretion and excessive concentration of tetraethylammonium in the blood.  (Taubert, Jonker)

Kim Kramer
Health Education Information and Resource Services (HEIRS)
http://www.heirs-online.com/
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Fibromyalgia, Endoplasmic Reticulum Stress, Neurotoxicity and CAMKII

Many experts now believe pain sensitivity in fibromyalgia is in part, neuropathic pain. "Martinez-Lavin notes that neuropathic pain is stimuli-independent and is accompanied by allodynia and paresthesia, which are also common features of fibromyalgia. He also points out that the most important characteristic of neuropathic pain is not the nerve lesion, but the resulting nerve dysfunction." (Kelly) Nociceptors (ie. TRPV1) can be upregulated in neuropathic conditions in addition to other inflammatory pain disorders. Also, a number of different agents activate nociceptors including those in food, fragrances and chemicals and other noxious stimuli like heat, cold and pH. Hormonals and neurochemical signals such as IGF and H2O2 and cytokines such as MCP-1 can increase the sensitivity of nociceptors which reduce their threshold for activation.
Upon activation of TRP channels, there is a flood of calcium inside the cell. Consistent and long-term activation and subsequent intracellular exposure to increased calcium may result in endoplasmic reticulum stress. Two consequences occur from ER stress 1) the activation of Nrf2 through PERK (Ho) which in endothelium includes Ho-1 binding to Nrf2 (Liu) and the 2) activation of CAMKII which may increase levels of cytokines and increase the likelihood of neuronal damage if not prevented. In cardiac cells, the inhibition of an isoform of CAMKII protects against intracellular levels of Ca+, H2O2 and acidosis in addition to protection from mitochondrial-induced apoptosis. Generally, H2O2 is generated through several mechanisms including from the mitochondrial respiratory chain and from activation of NADPH oxidases and can increase significantly during mitochondrial dysfunction. H2O2 signaling exerts prolonged signaling effects including those on dopamine release and down-regulation of CAMKII helps to prevent dopamine neurotoxicity(Cai, Bao). The activation of CAMKII from oxidative stress as noted by Xie, is responsible for "arrhythmia in diseased hearts and the heart's response to catecholamines in the "flight-fright" response (Cai). Also, CAMKII interacts with both TRPV1 and the NMDA receptor to alter their function. As for the latter, it may inhibit the downregulation of the NMDA receptor and increase the potential for pain generation and neurotoxicity.
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