If this is your first visit, be sure to check out the FAQ by clicking the link above. You may have to register before you can post: click the register link above to proceed. To start viewing messages, select the forum that you want to visit from the selection below. |
|
|
Thread Tools | Display Modes |
#21
|
|||
|
|||
Mitochondria & Mercury
On Mar 20, 12:33*pm, The One True Zhen Jue
wrote: On Mar 20, 12:23*pm, wrote: On Mar 20, 11:25*am, Bee wrote: On Mar 20, 12:17*am, "Jan Drew" wrote: Agent "D"--thought you'd enjoy this as an "interesting read" on Mercury. http://heartspring.net/mercury_poison_symptoms.html Nice article Bee. The article states: Organic compounds of mercury such as methylmercury are considered the most toxic forms of the element. Exposures to very small amounts of these compounds can result in devastating neurological damage and death. For fetuses, infants and children, the primary health effects of mercury are on neurological development. Even low levels of mercury exposure such as result from mother's consumption methylmercury in dietary sources can adversely affect the brain and nervous system. Impacts on memory, attention, language and other skills have been found in children exposed to moderate levels in the womb. Two questions about this. *The level of methylmercury in fish is very low. *How much is absorbed from the gut? *The absorbed amount must be no more than 3 to 5% I would think. *Anyone got the absorption data? Secondly, just how much more toxic is ethylmercury from thimerosal since it is more toxic than methyl mercury and 100% of it is absorbed due to being injected. So, you're saying that injecting something translates into 100% absorption. You're even dumber than we gave you credit for being and we extended you more credit than the prime-plus housing market. DrCee You cannot secure nor restore health with pus or poisons.- Hide quoted text - - Show quoted text -- Hide quoted text - - Show quoted text - Hey Zen man. Who are you referring to when you say "we" Is it the "gang" |
#22
|
|||
|
|||
Mitochondria & Mercury
On Mar 20, 1:10*pm, Kulacz wrote:
On Mar 20, 12:33*pm, The One True Zhen Jue wrote: On Mar 20, 12:23*pm, wrote: On Mar 20, 11:25*am, Bee wrote: On Mar 20, 12:17*am, "Jan Drew" wrote: Agent "D"--thought you'd enjoy this as an "interesting read" on Mercury. http://heartspring.net/mercury_poison_symptoms.html Nice article Bee. The article states: Organic compounds of mercury such as methylmercury are considered the most toxic forms of the element. Exposures to very small amounts of these compounds can result in devastating neurological damage and death. For fetuses, infants and children, the primary health effects of mercury are on neurological development. Even low levels of mercury exposure such as result from mother's consumption methylmercury in dietary sources can adversely affect the brain and nervous system. Impacts on memory, attention, language and other skills have been found in children exposed to moderate levels in the womb. Two questions about this. *The level of methylmercury in fish is very low. *How much is absorbed from the gut? *The absorbed amount must be no more than 3 to 5% I would think. *Anyone got the absorption data? Secondly, just how much more toxic is ethylmercury from thimerosal since it is more toxic than methyl mercury and 100% of it is absorbed due to being injected. So, you're saying that injecting something translates into 100% absorption. You're even dumber than we gave you credit for being and we extended you more credit than the prime-plus housing market. DrCee You cannot secure nor restore health with pus or poisons.- Hide quoted text - - Show quoted text -- Hide quoted text - - Show quoted text - Hey Zen man. Who are you referring to when you say "we" Is it the "gang"- Hide quoted text - The obvious answer is that I'm (properly) using the royal plural. But since you've asked politely, I'll let you in on MHA's biggest secret. Peter Bowditch is the only actual person here, all others, including you & I, are merely sock puppets. Now you know the truth, these comments are not posted by me, they are posted THROUGH me. - Show quoted text - |
#23
|
|||
|
|||
Mitochondria & Mercury
In article ,
wrote: On Mar 20, 11:25*am, Bee wrote: On Mar 20, 12:17*am, "Jan Drew" wrote: Agent "D"--thought you'd enjoy this as an "interesting read" on Mercury. http://heartspring.net/mercury_poison_symptoms.html Nice article Bee. The article states: Organic compounds of mercury such as methylmercury are considered the most toxic forms of the element. Exposures to very small amounts of these compounds can result in devastating neurological damage and death. For fetuses, infants and children, the primary health effects of mercury are on neurological development. Even low levels of mercury exposure such as result from mother's consumption methylmercury in dietary sources can adversely affect the brain and nervous system. Impacts on memory, attention, language and other skills have been found in children exposed to moderate levels in the womb. Two questions about this. The level of methylmercury in fish is very low. How much is absorbed from the gut? The absorbed amount must be no more than 3 to 5% I would think. Anyone got the absorption data? "Methyl mercury is 95%-100% absorbed through the gut. It penetrates the blood brain barrier and the placenta. Elemental mercury vapors are 75%-85% absorbed. Elemental mercury is not well absorbed in the gut, but in the presence of yeast and unhealthy flora. It can be converted to methyl mercury and therefore absorbed. Inorganic mercury has 7-15% absorption through the gut and 2-3% absorption through the skin." So much for your keen intuition, Cee. You were only off by an order of magnitude. Secondly, just how much more toxic is ethylmercury from thimerosal since it is more toxic than methyl mercury and 100% of it is absorbed due to being injected. And then excreted, mostly via the feces. A little detail that, like so many others, escapes you. -- David Wright :: alphabeta at copper.net These are my opinions only, but they're almost always correct. "Without Bush, what will America's schoolchildren have to look down on?" -- Bill Maher |
#24
|
|||
|
|||
Mitochondria & Mercury
wrote On Mar 19, 7:03 pm, "Jan Drew" wrote: Go to Pubmed and type in mitochondria and mercury. You will get links to 299 papers which explain exactly what mercury does to mitochondria. I went to Pubmed and found 299 articles on mitochondria and mercury. All the articles were discussing inorganic mercury or methylmercury. The various creatures studied were rats, Javan mongoose, dicentrarchus labrax, the frog Rana Kl escolenta, porcine kidney and liver, zebra fish, etc. Since thimerosal has ethylmercury and no studies were done on human tissue, am I correct in concluding that there is no valid scientific data to implicate the mercury in thimerosal to human disease whether inhaled, ingested, or injected? DrCee You cannot secure nor restore health with pus or poisons. All you need to do is type *in humans* You should know that! http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Histo-cytological responses of Dicentrarchus labrax (L.) following mercury exposure. Giari L, Simoni E, Manera M, Dezfuli BS. Department of Biology and Evolution, University of Ferrara, Via Borsari, 46, 44100 Ferrara, Italy. This work deals with the damaging effects of mercury (Hg concentrations 251, 355, 501mugl(-1)) on the structure and ultrastructure of gills, liver, intestine and kidney of farmed European sea bass (Dicentrarchus labrax L., 1758) acutely treated for 24 and 48h. The histoarchitecture of the gills of exposed fish was highly modified due to severe oedema, telangiectasia and secondary lamellar fusion. In hepatocytes and enterocytes hydropic cell swelling, alterations to the endoplasmic reticulum and mitochondria were noted, in addition to an abundance of myelinoid bodies which were frequently encountered following treatment. In the intestine and renal tubules of exposed European sea bass, rodlet cells (RCs) displayed ultrastructural modifications. Statistical analyses were conducted on the number and the size of selected cell types and structures. Following exposure to mercury for 24 and 48h, the number of chloride cells, RCs and macrophage aggregates were found to have increased significantly in the gills, the intestine and the head kidney. PMID: 17945343 [PubMed - as supplied by publisher] http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Aschner M, Syversen T, Souza DO, Rocha JB, Farina M. Departments of Pediatrics and Pharmacology, Vanderbilt University Medical Center, B3307 Medical Center North, Nashville, TN 37232, USA. This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage. PMID: 17334523 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Brain Res. 2007 Feb 2;1131(1):1-10. Epub 2006 Dec 19. Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M, Albrecht J, Aschner M. Department of Pediatrics, Vanderbilt University Medical Center, TN, USA. The neurotoxicity of high levels of methylmercury (MeHg) is well established both in humans and experimental animals. Astrocytes accumulate MeHg and play a prominent role in mediating MeHg toxicity in the central nervous system (CNS). Although the precise mechanisms of MeHg neurotoxicity are ill-defined, oxidative stress and altered mitochondrial and cell membrane permeability appear to be critical factors in its pathogenesis. The present study examined the effects of MeHg treatment on oxidative injury, mitochondrial inner membrane potential, glutamine uptake and expression of glutamine transporters in primary astrocyte cultures. MeHg caused a significant increase in F(2)-isoprostanes (F(2)-IsoPs), lipid peroxidation biomarkers of oxidative damage, in astrocyte cultures treated with 5 or 10 microM MeHg for 1 or 6 h. Consistent with this observation, MeHg induced a concentration-dependant reduction in the inner mitochondrial membrane potential (DeltaPsi(m)), as assessed by the potentiometric dye, tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate that DeltaPsi(m) is a very sensitive endpoint for MeHg toxicity, since significant reductions were observed after only 1 h exposure to concentrations of MeHg as low as 1 microM. MeHg pretreatment (1, 5 and 10 microM) for 30 min also inhibited the net uptake of glutamine ((3)H-glutamine) measured at 1 min and 5 min. Expression of the mRNA coding the glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at the highest (10 microM) MeHg concentration, suggesting that the reduction in glutamine uptake observed after 30 min treatment with lower concentrations of MeHg (1 and 5 microM) was not due to inhibition of transcription. Taken together, these studies demonstrate that MeHg exposure is associated with increased mitochondrial membrane permeability, alterations in glutamine/glutamate cycling, increased ROS formation and consequent oxidative injury. Ultimately, MeHg initiates multiple additive or synergistic disruptive mechanisms that lead to cellular dysfunction and cell death. PMID: 17182013 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1...d_RVDocSumChem Res Toxicol. 2006 Aug;19(8):1080-5.Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH.Institute of Toxicology, Department of Laboratory Medicine, and Departmentof Orthopaedics, College of Medicine, National Taiwan University, Taipei,Taiwan.Mercury is a well-known toxic metal, which induces oxidative stress.Pancreatic beta-cells are vulnerable to oxidative stress. Thepathophysiological effect of mercury on the function of pancreaticbeta-cells remains unclear. The present study was designed to investigatethe effects of methylmercury (MeHg)-induced oxidative stress on the cellviability and function of pancreatic beta-cells. The number of viable cellswas reduced 24 h after MeHg treatment in a dose-dependent manner with arange from 1 to 20 microM. 2',7'-Dichlorofluorescein fluorescence as anindicator of reactive oxygen species (ROS) formation after exposure ofHIT-T15 cells or isolated mouse pancreatic islets to MeHg significantlyincreased ROS levels. MeHg could also suppress insulin secretion in HIT-T15cells and isolated mouse pancreatic islets. After 24 h of exposure to MeHg,HIT-T15 cells had a significant increase in mercury levels with adose-dependent manner. Moreover, MeHg displayed several features of cellapoptosis including an increase of the sub-G1 population and annexin-Vbinding. Treatment of HIT-T15 cells with MeHg resulted in disruption of themitochondrial membrane potential and release of cytochrome c from themitochondria to the cytosol and activation of caspase-3. AntioxidantN-acetylcysteine effectively reversed the MeHg-induced cellular responses.Altogether, our data clearly indicate that MeHg-induced oxidative stresscauses pancreatic beta-cell apoptosis and dysfunction.PMID: 16918248 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16764493?ordinalpos=9&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: J Prev Med Pub Health. 2006 May;39(3):199-204.[Mercuric chloride induces apoptosis in MDCK cells][Article in Korean]Lee JH, Youm JH, Kwon KS.Department of Preventive Medicine and Public Health, School of MedicineChonbuk National University.OBJECTIVES: Mercury is a hazardous organ-specific environmental contaminant.It exists in a wide variety of physical and chemical states, each of whichhas unique characteristics for the target organ specificity. Exposure tomercury vapor and to organic mercury compounds specifically affects the CNS,while the kidney is the target organ for inorganic Hg compounds. METHODS: Inthis study, mercury chloride (HgCl2) was studied in a renal derived cellsystem, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cellline, which has specific sensitivity to the toxic effect of mercury. MDCKcells were cultured for 6-24 hr in vitro in various concentrations (0.1-100M) of HgCl2, and the markers of apoptosis or cell death were assayed,including DNA fragmentation, caspase-3 activity andwestern blotting ofcytochrome c. The influence of the metal on cell proliferation and viabilitywere evaluated by the conventional MTT test. RESULTS: The cell viability wasdecreased in a time and concentration dependent fashion: decreases werenoted at 6, 12 and 24 hr after HgCl2 exposure. The increases of DNAfragmentation were also observed in the concentrations from 0.1 to 10 M ofHgCl2 at 6 hr after exposure. However, we could not observe DNAfragmentation in the concentrations more than 25 M because the cells rapidlyproceeded to necrotic cell death. The activation of caspase-3 was alsoobserved at 6 hr exposure in the HgCl2 concentrations from 0.1 to 10 M. Therelease of cytochrome c from the mitochondria into the cytosol, which is aninitiator of the activation of the caspase cascade, was also observed in theHgCl2-treated MDCK cells. CONCLUSIONS: These results suggest that theactivation of caspase-3 was involved in HgCl2-induced apoptosis. The releaseof cytochrome c from the mitochondria into the cytosol was also observed inthe HgCl2-treated MDCK cells. These findings indicate that in MDCK cells,HgCl2 is a potent inducer of apoptosis via cytochrome c release from themitochondria.PMID: 16764493 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16457873?ordinalpos=11&itool=EntrezSystem2.PEntrez .Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: Sci Total Environ. 2006 Aug 1;366(2-3):627-37. Epub 2006 Feb 7Accumulation of mercury, selenium and their binding proteins in porcinekidney and liver from mercury-exposed areas with the investigation of theirredox responses.Chen C, Qu L, Zhao J, Liu S, Deng G, Li B, Zhang P, Chai Z.Key Laboratory of Nuclear Analytical Techniques and Institute of High EnergyPhysics, Chinese Academy of Sciences, P. O. Box 918, Beijing 100039, PRChina. e subcellular localization of Se and Hg and their cytosolic bindingproteins, including cellular oxidative status, in porcine liver and kidneyhave been studied by using samples from a chronic Hg-contaminated area and anon-Hg-contaminated area. Coaccumulation and redistribution of Se and Hg insubcellular fractions due to mercury exposure were found. The Hg and Seconcentrations in tissues from Hg-exposed porcine were 80 fold and 5-20 foldhigher than controls, respectively. Interestingly, the retention of both Seand Hg increased 10% in mitochondria, while decreased 10% in cytosol ofHg-exposed pig liver. Mercury was mainly in the form of MTs in the cytosolof the non-Hg-exposed porcine kidney. MT binds Hg in the cytosol withlimited capacity, and the rest Hg was redistributed to the high molecularweight (MW) proteins (80-100 kDa) in the Hg-exposed group. Thecoaccumulation of Hg and Se was also found in high MW proteins, where theirmolar ratio tended to be 1:1. Moreover, the Se-containing polypeptides (3-6kDa) increased significantly both in hepatic and renal cytosol of theHg-exposed pigs. Se-dependent GSH-Px and SOD activity were increased to copewith Hg-induced oxidative stress. In previous studies, the roles of Se andMTs were generally taken into account separately; we discussed theircombining roles in the case of high Hg exposure. The present results werebeneficial to understand the existing states of Hg in vivo and evaluate theinteraction of toxic and essential elements.PMID: 16457873 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/17182013?ordinalpos=1&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: Brain Res. 2007 Feb 2;1131(1):1-10. Epub 2006 Dec 19. LinksMethylmercury induces oxidative injury, alterations in permeability andglutamine transport in cultured astrocytes.Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M,Albrecht J, Aschner M.Department of Pediatrics, Vanderbilt University Medical Center, TN, USA.The neurotoxicity of high levels of methylmercury (MeHg) is well establishedboth in humans and experimental animals. Astrocytes accumulate MeHg and playa prominent role in mediating MeHg toxicity in the central nervous system(CNS). Although the precise mechanisms of MeHg neurotoxicity areill-defined, oxidative stress and altered mitochondrial and cell membranepermeability appear to be critical factors in its pathogenesis. The presentstudy examined the effects of MeHg treatment on oxidative injury,mitochondrial inner membrane potential, glutamine uptake and expression ofglutamine transporters in primary astrocyte cultures. MeHg caused asignificant increase in F(2)-isoprostanes (F(2)-IsoPs), lipid peroxidationbiomarkers of oxidative damage, in astrocyte cultures treated with 5 or 10microM MeHg for 1 or 6 h. Consistent with this observation, MeHg induced aconcentration-dependant reduction in the inner mitochondrial membranepotential (DeltaPsi(m)), as assessed by the potentiometric dye,tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate thatDeltaPsi(m) is a very sensitive endpoint for MeHg toxicity, sincesignificant reductions were observed after only 1 h exposure toconcentrations of MeHg as low as 1 microM. MeHg pretreatment (1, 5 and 10microM) for 30 min also inhibited the net uptake of glutamine((3)H-glutamine) measured at 1 min and 5 min. Expression of the mRNA codingthe glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at thehighest (10 microM) MeHg concentration, suggesting that the reduction inglutamine uptake observed after 30 min treatment with lower concentrationsof MeHg (1 and 5 microM) was not due to inhibition of transcription. Takentogether, these studies demonstrate that MeHg exposure is associated withincreased mitochondrial membrane permeability, alterations inglutamine/glutamate cycling, increased ROS formation and consequentoxidative injury. Ultimately, MeHg initiates multiple additive orsynergistic disruptive mechanisms that lead to cellular dysfunction and celldeath.PMID: 17182013 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16366737?ordinalpos=2&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumNeurodeg eneration from mitochondrial insufficiency: nutrients, stem cells,growth factors, and prospects for brain rebuilding using integrativemanagement.Kidd PM.University of California, Berkeley, USA. egenerative brain disorders (neurodegeneration) can be frustrating for bothconventional and alternative practitioners. A more comprehensive,integrative approach is urgently needed. One emerging focus for interventionis brain energetics. Specifically, mitochondrial insufficiency contributesto the etiopathology of many such disorders. Electron leakages inherent tomitochondrial energetics generate reactive oxygen free radical species thatmay place the ultimate limit on lifespan. Exogenous toxins, such as mercuryand other environmental contaminants, exacerbate mitochondrial electronleakage, hastening their demise and that of their host cells. Studies of thebrain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson'sdisease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington'sdisease, Friedreich's ataxia, aging, and constitutive disorders demonstrateimpairments of the mitochondrial citric acid cycle and oxidativephosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequentlyreveal energetic insufficiency and depleted energy reserve in brain tissuein situ. Orthomolecular nutrients involved in mitochondrial metabolismprovide clinical benefit. Among these are the essential minerals and the Bvitamin group; vitamins E and K; and the antioxidant and energetic cofactorsalpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamideadenine dinucleotide, reduced (NADH). Recent advances in the area of stemcells and growth factors encourage optimism regarding brain regeneration.The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine(GPC), and phosphatidylserine (PS) provide mitochondrial support andconserve growth factor receptors; all three improved cognition indouble-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) isenzymatically combined with GPC and PS to form membrane phospholipids fornerve cell expansion. Practical recommendations are presented forintegrating these safe and well-tolerated orthomolecular nutrients into acomprehensive dietary supplementation program for brain vitality andproductive lifespan.PMID: 16366737 [PubMed - indexed for MEDLINE] |
#25
|
|||
|
|||
Mitochondria & Mercury
DrCee You cannot secure nor restore health with pus or poisons. On Mar 19, 7:03 pm, "Jan Drew" wrote: Go to Pubmed and type in mitochondria and mercury. You will get links to 299 papers which explain exactly what mercury does to mitochondria. I went to Pubmed and found 299 articles on mitochondria and mercury. All the articles were discussing inorganic mercury or methylmercury. The various creatures studied were rats, Javan mongoose, dicentrarchus labrax, the frog Rana Kl escolenta, porcine kidney and liver, zebra fish, etc. Since thimerosal has ethylmercury and no studies were done on human tissue, am I correct in concluding that there is no valid scientific data to implicate the mercury in thimerosal to human disease whether inhaled, ingested, or injected? DrCee You cannot secure nor restore health with pus or poisons. Incorrect. There are indeed Studies on humans. http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Histo-cytological responses of Dicentrarchus labrax (L.) following mercury exposure. Giari L, Simoni E, Manera M, Dezfuli BS. Department of Biology and Evolution, University of Ferrara, Via Borsari, 46, 44100 Ferrara, Italy. This work deals with the damaging effects of mercury (Hg concentrations 251, 355, 501mugl(-1)) on the structure and ultrastructure of gills, liver, intestine and kidney of farmed European sea bass (Dicentrarchus labrax L., 1758) acutely treated for 24 and 48h. The histoarchitecture of the gills of exposed fish was highly modified due to severe oedema, telangiectasia and secondary lamellar fusion. In hepatocytes and enterocytes hydropic cell swelling, alterations to the endoplasmic reticulum and mitochondria were noted, in addition to an abundance of myelinoid bodies which were frequently encountered following treatment. In the intestine and renal tubules of exposed European sea bass, rodlet cells (RCs) displayed ultrastructural modifications. Statistical analyses were conducted on the number and the size of selected cell types and structures. Following exposure to mercury for 24 and 48h, the number of chloride cells, RCs and macrophage aggregates were found to have increased significantly in the gills, the intestine and the head kidney. PMID: 17945343 [PubMed - as supplied by publisher] http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity. Aschner M, Syversen T, Souza DO, Rocha JB, Farina M. Departments of Pediatrics and Pharmacology, Vanderbilt University Medical Center, B3307 Medical Center North, Nashville, TN 37232, USA. This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage. PMID: 17334523 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum Brain Res. 2007 Feb 2;1131(1):1-10. Epub 2006 Dec 19. Methylmercury induces oxidative injury, alterations in permeability and glutamine transport in cultured astrocytes. Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M, Albrecht J, Aschner M. Department of Pediatrics, Vanderbilt University Medical Center, TN, USA. The neurotoxicity of high levels of methylmercury (MeHg) is well established both in humans and experimental animals. Astrocytes accumulate MeHg and play a prominent role in mediating MeHg toxicity in the central nervous system (CNS). Although the precise mechanisms of MeHg neurotoxicity are ill-defined, oxidative stress and altered mitochondrial and cell membrane permeability appear to be critical factors in its pathogenesis. The present study examined the effects of MeHg treatment on oxidative injury, mitochondrial inner membrane potential, glutamine uptake and expression of glutamine transporters in primary astrocyte cultures. MeHg caused a significant increase in F(2)-isoprostanes (F(2)-IsoPs), lipid peroxidation biomarkers of oxidative damage, in astrocyte cultures treated with 5 or 10 microM MeHg for 1 or 6 h. Consistent with this observation, MeHg induced a concentration-dependant reduction in the inner mitochondrial membrane potential (DeltaPsi(m)), as assessed by the potentiometric dye, tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate that DeltaPsi(m) is a very sensitive endpoint for MeHg toxicity, since significant reductions were observed after only 1 h exposure to concentrations of MeHg as low as 1 microM. MeHg pretreatment (1, 5 and 10 microM) for 30 min also inhibited the net uptake of glutamine ((3)H-glutamine) measured at 1 min and 5 min. Expression of the mRNA coding the glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at the highest (10 microM) MeHg concentration, suggesting that the reduction in glutamine uptake observed after 30 min treatment with lower concentrations of MeHg (1 and 5 microM) was not due to inhibition of transcription. Taken together, these studies demonstrate that MeHg exposure is associated with increased mitochondrial membrane permeability, alterations in glutamine/glutamate cycling, increased ROS formation and consequent oxidative injury. Ultimately, MeHg initiates multiple additive or synergistic disruptive mechanisms that lead to cellular dysfunction and cell death. PMID: 17182013 [PubMed - indexed for MEDLINE] http://www.ncbi.nlm.nih.gov/pubmed/1...d_RVDocSumChem Res Toxicol. 2006 Aug;19(8):1080-5.Methylmercury induces pancreatic beta-cell apoptosis and dysfunction.Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang CY, Lin-Shiau SY, Liu SH.Institute of Toxicology, Department of Laboratory Medicine, and Departmentof Orthopaedics, College of Medicine, National Taiwan University, Taipei,Taiwan.Mercury is a well-known toxic metal, which induces oxidative stress.Pancreatic beta-cells are vulnerable to oxidative stress. Thepathophysiological effect of mercury on the function of pancreaticbeta-cells remains unclear. The present study was designed to investigatethe effects of methylmercury (MeHg)-induced oxidative stress on the cellviability and function of pancreatic beta-cells. The number of viable cellswas reduced 24 h after MeHg treatment in a dose-dependent manner with arange from 1 to 20 microM. 2',7'-Dichlorofluorescein fluorescence as anindicator of reactive oxygen species (ROS) formation after exposure ofHIT-T15 cells or isolated mouse pancreatic islets to MeHg significantlyincreased ROS levels. MeHg could also suppress insulin secretion in HIT-T15cells and isolated mouse pancreatic islets. After 24 h of exposure to MeHg,HIT-T15 cells had a significant increase in mercury levels with adose-dependent manner. Moreover, MeHg displayed several features of cellapoptosis including an increase of the sub-G1 population and annexin-Vbinding. Treatment of HIT-T15 cells with MeHg resulted in disruption of themitochondrial membrane potential and release of cytochrome c from themitochondria to the cytosol and activation of caspase-3. AntioxidantN-acetylcysteine effectively reversed the MeHg-induced cellular responses.Altogether, our data clearly indicate that MeHg-induced oxidative stresscauses pancreatic beta-cell apoptosis and dysfunction.PMID: 16918248 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16764493?ordinalpos=9&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: J Prev Med Pub Health. 2006 May;39(3):199-204.[Mercuric chloride induces apoptosis in MDCK cells][Article in Korean]Lee JH, Youm JH, Kwon KS.Department of Preventive Medicine and Public Health, School of MedicineChonbuk National University.OBJECTIVES: Mercury is a hazardous organ-specific environmental contaminant.It exists in a wide variety of physical and chemical states, each of whichhas unique characteristics for the target organ specificity. Exposure tomercury vapor and to organic mercury compounds specifically affects the CNS,while the kidney is the target organ for inorganic Hg compounds. METHODS: Inthis study, mercury chloride (HgCl2) was studied in a renal derived cellsystem, i.e., the tubular epithelial Madin-Darby canine kidney (MDCK) cellline, which has specific sensitivity to the toxic effect of mercury. MDCKcells were cultured for 6-24 hr in vitro in various concentrations (0.1-100M) of HgCl2, and the markers of apoptosis or cell death were assayed,including DNA fragmentation, caspase-3 activity andwestern blotting ofcytochrome c. The influence of the metal on cell proliferation and viabilitywere evaluated by the conventional MTT test. RESULTS: The cell viability wasdecreased in a time and concentration dependent fashion: decreases werenoted at 6, 12 and 24 hr after HgCl2 exposure. The increases of DNAfragmentation were also observed in the concentrations from 0.1 to 10 M ofHgCl2 at 6 hr after exposure. However, we could not observe DNAfragmentation in the concentrations more than 25 M because the cells rapidlyproceeded to necrotic cell death. The activation of caspase-3 was alsoobserved at 6 hr exposure in the HgCl2 concentrations from 0.1 to 10 M. Therelease of cytochrome c from the mitochondria into the cytosol, which is aninitiator of the activation of the caspase cascade, was also observed in theHgCl2-treated MDCK cells. CONCLUSIONS: These results suggest that theactivation of caspase-3 was involved in HgCl2-induced apoptosis. The releaseof cytochrome c from the mitochondria into the cytosol was also observed inthe HgCl2-treated MDCK cells. These findings indicate that in MDCK cells,HgCl2 is a potent inducer of apoptosis via cytochrome c release from themitochondria.PMID: 16764493 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16457873?ordinalpos=11&itool=EntrezSystem2.PEntrez .Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: Sci Total Environ. 2006 Aug 1;366(2-3):627-37. Epub 2006 Feb 7Accumulation of mercury, selenium and their binding proteins in porcinekidney and liver from mercury-exposed areas with the investigation of theirredox responses.Chen C, Qu L, Zhao J, Liu S, Deng G, Li B, Zhang P, Chai Z.Key Laboratory of Nuclear Analytical Techniques and Institute of High EnergyPhysics, Chinese Academy of Sciences, P. O. Box 918, Beijing 100039, PRChina. e subcellular localization of Se and Hg and their cytosolic bindingproteins, including cellular oxidative status, in porcine liver and kidneyhave been studied by using samples from a chronic Hg-contaminated area and anon-Hg-contaminated area. Coaccumulation and redistribution of Se and Hg insubcellular fractions due to mercury exposure were found. The Hg and Seconcentrations in tissues from Hg-exposed porcine were 80 fold and 5-20 foldhigher than controls, respectively. Interestingly, the retention of both Seand Hg increased 10% in mitochondria, while decreased 10% in cytosol ofHg-exposed pig liver. Mercury was mainly in the form of MTs in the cytosolof the non-Hg-exposed porcine kidney. MT binds Hg in the cytosol withlimited capacity, and the rest Hg was redistributed to the high molecularweight (MW) proteins (80-100 kDa) in the Hg-exposed group. Thecoaccumulation of Hg and Se was also found in high MW proteins, where theirmolar ratio tended to be 1:1. Moreover, the Se-containing polypeptides (3-6kDa) increased significantly both in hepatic and renal cytosol of theHg-exposed pigs. Se-dependent GSH-Px and SOD activity were increased to copewith Hg-induced oxidative stress. In previous studies, the roles of Se andMTs were generally taken into account separately; we discussed theircombining roles in the case of high Hg exposure. The present results werebeneficial to understand the existing states of Hg in vivo and evaluate theinteraction of toxic and essential elements.PMID: 16457873 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/17182013?ordinalpos=1&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum1: Brain Res. 2007 Feb 2;1131(1):1-10. Epub 2006 Dec 19. LinksMethylmercury induces oxidative injury, alterations in permeability andglutamine transport in cultured astrocytes.Yin Z, Milatovic D, Aschner JL, Syversen T, Rocha JB, Souza DO, Sidoryk M,Albrecht J, Aschner M.Department of Pediatrics, Vanderbilt University Medical Center, TN, USA.The neurotoxicity of high levels of methylmercury (MeHg) is well establishedboth in humans and experimental animals. Astrocytes accumulate MeHg and playa prominent role in mediating MeHg toxicity in the central nervous system(CNS). Although the precise mechanisms of MeHg neurotoxicity areill-defined, oxidative stress and altered mitochondrial and cell membranepermeability appear to be critical factors in its pathogenesis. The presentstudy examined the effects of MeHg treatment on oxidative injury,mitochondrial inner membrane potential, glutamine uptake and expression ofglutamine transporters in primary astrocyte cultures. MeHg caused asignificant increase in F(2)-isoprostanes (F(2)-IsoPs), lipid peroxidationbiomarkers of oxidative damage, in astrocyte cultures treated with 5 or 10microM MeHg for 1 or 6 h. Consistent with this observation, MeHg induced aconcentration-dependant reduction in the inner mitochondrial membranepotential (DeltaPsi(m)), as assessed by the potentiometric dye,tetramethylrhodamine ethyl ester (TMRE). Our results demonstrate thatDeltaPsi(m) is a very sensitive endpoint for MeHg toxicity, sincesignificant reductions were observed after only 1 h exposure toconcentrations of MeHg as low as 1 microM. MeHg pretreatment (1, 5 and 10microM) for 30 min also inhibited the net uptake of glutamine((3)H-glutamine) measured at 1 min and 5 min. Expression of the mRNA codingthe glutamine transporters, SNAT3/SN1 and ASCT2, was inhibited only at thehighest (10 microM) MeHg concentration, suggesting that the reduction inglutamine uptake observed after 30 min treatment with lower concentrationsof MeHg (1 and 5 microM) was not due to inhibition of transcription. Takentogether, these studies demonstrate that MeHg exposure is associated withincreased mitochondrial membrane permeability, alterations inglutamine/glutamate cycling, increased ROS formation and consequentoxidative injury. Ultimately, MeHg initiates multiple additive orsynergistic disruptive mechanisms that lead to cellular dysfunction and celldeath.PMID: 17182013 [PubMed - indexed for MEDLINE]http://www.ncbi.nlm.nih.gov/pubmed/16366737?ordinalpos=2&itool=EntrezSystem2.PEntrez. Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSumNeurodeg eneration from mitochondrial insufficiency: nutrients, stem cells,growth factors, and prospects for brain rebuilding using integrativemanagement.Kidd PM.University of California, Berkeley, USA. egenerative brain disorders (neurodegeneration) can be frustrating for bothconventional and alternative practitioners. A more comprehensive,integrative approach is urgently needed. One emerging focus for interventionis brain energetics. Specifically, mitochondrial insufficiency contributesto the etiopathology of many such disorders. Electron leakages inherent tomitochondrial energetics generate reactive oxygen free radical species thatmay place the ultimate limit on lifespan. Exogenous toxins, such as mercuryand other environmental contaminants, exacerbate mitochondrial electronleakage, hastening their demise and that of their host cells. Studies of thebrain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson'sdisease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington'sdisease, Friedreich's ataxia, aging, and constitutive disorders demonstrateimpairments of the mitochondrial citric acid cycle and oxidativephosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequentlyreveal energetic insufficiency and depleted energy reserve in brain tissuein situ. Orthomolecular nutrients involved in mitochondrial metabolismprovide clinical benefit. Among these are the essential minerals and the Bvitamin group; vitamins E and K; and the antioxidant and energetic cofactorsalpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamideadenine dinucleotide, reduced (NADH). Recent advances in the area of stemcells and growth factors encourage optimism regarding brain regeneration.The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine(GPC), and phosphatidylserine (PS) provide mitochondrial support andconserve growth factor receptors; all three improved cognition indouble-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) isenzymatically combined with GPC and PS to form membrane phospholipids fornerve cell expansion. Practical recommendations are presented forintegrating these safe and well-tolerated orthomolecular nutrients into acomprehensive dietary supplementation program for brain vitality andproductive lifespan.PMID: 16366737 [PubMed - indexed for MEDLINE] |
Thread Tools | |
Display Modes | |
|
|
Similar Threads | ||||
Thread | Thread Starter | Forum | Replies | Last Post |
Mitochondria & Mercury | Jan Drew | General | 24 | March 21st 08 05:45 AM |
Rep. Dan Burton Addresses Congress on Mercury: Cites New Evidence Showing Mercury Connection to Autism | Ilena Rose | Kids Health | 23 | December 17th 07 01:40 PM |
Rep. Dan Burton Addresses Congress on Mercury: Cites New Evidence Showing Mercury Connection to Autism | Ilena Rose | Kids Health | 1 | December 15th 07 05:19 PM |
Danger to the fetus Mercury Exposure including mercury amagams- breast milk | Jan Drew | Kids Health | 15 | February 2nd 07 05:00 PM |
New Study Shows Vaccine Mercury Results In More Than Twice As Much Mercury Being Trapped In The Brain | Jan Drew | Kids Health | 7 | November 7th 06 12:11 AM |