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Medical Forum / Diseases and Disorders / Arthritis / January 2008Iron-chelating Cartilage-saving Plant-derived Drug
http://rheumatology.oxfordjournals.org/cgi/content/full/38/11/1088 Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis Abstract Objective. To investigate whether apocynin, 1-(4-hydroxy-3- methoxyphenyl)ethanone, is able to diminish inflammation-induced cartilage destruction in rheumatoid arthritis (RA), studied in a human in vitro model. Methods. Apocynin was added to cultures of RA peripheral blood mononuclear cells (PBMNC). Cartilage-destructive activity was determined by addition of culture supernatant to tissue samples of human articular cartilage. In addition, the proliferation of PBMNC, their production of tumour necrosis factor alpha (TN-F), interleukin (IL)-1 and IL-10, and T-cell production of interferon gamma (IFN-) and IL-4, as measures for T1 and T2 cell activity, were determined. Results. Apocynin was able to counteract RA PBMNC-induced inhibition of cartilage matrix proteoglycan synthesis, while no effect on inflammation-enhanced proteoglycan release was found. The effect was accompanied by a decrease in IL-1 and TNF- production by the MNC. No effect on T-cell proliferation was found, but the production of IFN-, IL-4 and T-cell-derived IL-10 was strongly diminished. Most important, apocynin did not show any direct adverse effects on chondrocyte metabolism; on the contrary, it diminished the release of proteoglycans from the cartilage matrix. Conclusion. Apocynin in vitro inhibits inflammation-mediated cartilage destruction without having adverse effects on cartilage. The latter may be an advantage of apocynin over many other non-steroidal anti- inflammatory drugs. Therefore, apocynin might have an added beneficial effect in protecting RA patients from joint destruction. KEY WORDS: Apocynin, Rheumatoid arthritis, Non-steroidal anti- inflammatory drugs, Cartilage F. P. J. G. Lafeber, C. J. Beukelman1, E. van den Worm1, J. L. A. M. van Roy, M. E. Vianen, J. A. G. van Roon, H. van Dijk1 and J. W. J. Bijlsma Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht and 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Utrecht University, The Netherlands Correspondence to: F. P. J. G. Lafeber, Department of Rheumatology and Clinical Immunology (F02.127), University Medical Centre Utrecht, PO Box 85500, 3508 GA Urecht, The Netherlands. Rheumatology 1999; 38: 1088-1093 © 1999 British Society for Rheumatology -------------------------------------------- http://tinyurl.com/ynpdhm "Iron-chelating agents, N-acetyl-L-cysteine (NAC), apocynin,probucol, and edaravone, are useful in preventing cardiovascular injury and diseases." Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > http://rheumatology.oxfordjournals.org/cgi/content/full/38/11/1088 From the full text: QUOTE: apocynin is anti-inflammatory as it interferes with arachidonic acid metabolism [16] UNQUOTE. Soo nothing new here ... Without arachidonic acid in our cells we don't have to worry about consuming enough plants and removing the iron! Taka On Jan 14, 6:30 pm, Taka <taka0...@gmail.com> wrote:interferes with arachidonic acid metabolism << So seeing apocynin is an iron chelator .. then one can dedeuce iron = arachidonic .. Logic .. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > >http://rheumatology.oxfordjournals.org/cgi/content/full/38/11/1088 > [quoted text clipped - 8 lines] > > Taka On Jan 14, 7:34 pm, ironjustice <teamtan...@hotmail.com> wrote:So seeing apocynin is an iron chelator .. then one can dedeuce iron = arachidonic << http://www.circ.ahajournals.org/cgi/content/abstract/103/19/2395 "Iron-overload-induced cardiomyopathy" "Iron overload enhances AA release and incorporation of AA into phosphatidylcholine" Basic Science Reports Increased Release of Arachidonic Acid and Eicosanoids in Iron- Overloaded Cardiomyocytes Rafael Mattera, PhD; Gregory P. Stone, BA; Nael Bahhur, BA; Yuri A. Kuryshev, PhD From Rammelkamp Center for Education and Research, MetroHealth Medical Center (R.M., G.P.S., N.B., Y.A.K.) and Department of Medicine (R.M.), Case Western Reserve University School of Medicine, Cleveland, Ohio. Correspondence to Rafael Mattera, PhD, Cell Biology and Metabolism Branch, NICHD, Building 18T, Room 101, Bethesda, MD 20892. E-mail matterar@helix.nih.gov Background--Patients with transfusional iron overload may develop a life-limiting cardiomyopathy. The sensitivity of lipid-metabolizing enzymes to peroxidative injury, as well as the reported effects of arachidonic acid (AA) and metabolites on cardiac rhythm, led us to hypothesize that iron-overloaded cardiomyocytes display alterations in the release of AA and prostaglandins. Methods and Results--Neonatal rat ventricular myocytes (NRVMs) cultured for 72 hours in the presence of 80 µg/mL ferric ammonium citrate displayed an increased rate of AA release, both under resting conditions and after stimulation with agonists such as [Sar1]Ang II. Although iron treatment did not affect overall incorporation of [3H]AA into NRVM phospholipids, it caused a 2-fold increase in the distribution of precursor in phosphatidylcholine species, with a proportional decrease in phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine. Increased release of AA in iron-overloaded NRVMs was reduced by the diacylglycerol lipase inhibitor RHC80267 but was largely insensitive to inhibitors of phospholipases A2 and C. Iron- overloaded cardiomyocytes also displayed increased production of eicosanoids and induction of cyclooxygenase-2 after stimulation with interleukin-1. Conclusions--Iron overload enhances AA release and incorporation of AA into phosphatidylcholine, as well as cyclooxygenase-2 induction and eicosanoid production, in NRVMs. The effects of AA and metabolites on cardiomyocyte rhythmicity suggest a causal connection between these signals and electromechanical alterations in iron-overload-induced cardiomyopathy. Key Words: cardiomyopathy * prostaglandins * signal transduction * myocytes * iron Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > On Jan 14, 6:30 pm, Taka <taka0...@gmail.com> wrote:interferes with > arachidonic acid metabolism << [quoted text clipped - 27 lines] > > - Show quoted text - > On Jan 14, 6:30 pm, Taka <taka0...@gmail.com> wrote:interferes with > arachidonic acid metabolism << [quoted text clipped - 3 lines] > > Logic .. You see Tom, the point is that you don't have to be overloaded with arachidonic acid to worry about your iron levels. Taka On Jan 14, 11:12 pm, Taka <taka0...@gmail.com> wrote:You see Tom, the point is that you don't have to be overloaded with arachidonic acid to worry about your iron levels. << I might have missed something but I believe the article says .. iron INDUCES and enhances the problem with arachidonic acid .. Sooo .. as I said .. iron = arachidonic .. Without the iron .. no arachidonic .. therefore no lipid peroxidation .. therefore no .. Taka .. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > > On Jan 14, 6:30 pm, Taka <taka0...@gmail.com> wrote:interferes with > > arachidonic acid metabolism << [quoted text clipped - 8 lines] > > Taka > On Jan 14, 11:12 pm, Taka <taka0...@gmail.com> wrote:You see Tom, the > point is that you don't have to be overloaded with arachidonic acid [quoted text clipped - 7 lines] > Without the iron .. no arachidonic .. therefore no lipid > peroxidation .. therefore no .. Taka .. Look at it this way: no arachidonic acid = no problems with iron You don't need the arachidonic acid to live but you DO need the iron for life. You would be dead soon without iron in your body in contrast to the arachidonic acid ... Taka On Jan 15, 5:04 pm, Taka <taka0...@gmail.com> wrote: you DO need the iron for life. You would be dead soon without iron in your body in contrast to the arachidonic acid ... << Now .. when one has .. 7 .. seven .. 7 .. months worth of **stored** iron in the body **at all times** .. would this fictitious .. scenario .. ever happen .. ? There is no way a person can have their iron levels lowered below that .. 7 .. seven .. 7 .. months worth of **stored** iron to any extent .. you would be LONG dead of starvation. Bloodied and battered .. ? It takes weeks of constant bloodletting to get a persons iron levels down .. with having to PULL it out of the stores in order to access .. it .. Sooo .. a good beating or even an extensive car wreck where you lost EVERY BIT OF BLOOD IN YOUR BODY .. will you be iron deficient .. ? .. not a .. chance .. because the body takes TIME to PULL that iron out of those **stores** .. be it in the tendonitis / hemosiderin .. joints / hemosiderin .. brain / hemosiderin .. etc. Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://tinyurl.com/a3cc3 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk > Taka |
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