Practiserelevant of chronic nitrosative stess
Chronic diseases never occur isolated, but as multisystem diseases or so-called comorbidities. They all have in common chronic nitrosative stress due to an enhanced synthesis of inducible nitric oxide (iNO). The effects are:
-Inhibition of enzymes of the mitochondrial respiration complexes containing FeS and Fe, of aconitase belonging to the citrate cycle, of 7a-hydroxylase and a related development of cholesterolemia, of peroxidases and haemsynthesis disorders.
- Initiation and promotion of inflammatory processes due to protein citrullination and COX activation. Chronic aseptic inflammations are developed accompanied by CrP-enhancement and autoimmune diseases.
- Inhibition of the neuronal and endothelial NO-synthesis as well as increase of asymmetrical dimethylarginin (ADMA).
- Blockade of mitochondria, energy deficiency, hyperactivity of receptors and inflammation engendering superoxide. Together with NO this produces toxic peroxynitrite.
- Peroxynitrite causes nitrosation of aromatic aminoacids and oxidation of SH groups, vitamin C, cholesterol. Because it concentrates in axones, it acts as a strong neurotoxin and irreversibly inhibits the function of mitochondria.
Vitamin B12 inhibits the synthesis of iNO. Thus chronic nitrosative stress triggers the deficiency of vitamin B12. Consequences are pathological synthesis of fatty acids, an additional inhibition of the oxidation of fatty acids and the citrate cycle as well as disturbances of the methylation in amine metabolism. Chronic energy deficiency induces neuronal and gastro-intestinal encephalomyopathies. The metabolizing of carbohydrates into fats increases inducing lactacidosis. Chronic nitrosative stress enhances the rate of mutations within the mitochondrial genome and the nucleic DNA of cells. The former is maternally inherited, the latter also paternally.
Chronic nitrosative stress means mitochondropathy. In this regard a change of paradigms in medicine is required concerning desease conception, diagnostics and therapy. There are new possibilities for treatment of chronic multisystem diseases. The effects are causally and at a reasonable price and are achievable merely by micronutrients including vitamin B12. Meanwhile numerous diseases could be identified as mitochondropathies. Their number will increase with the increasing yield of knowledge.
key words: nitric oxide, peroxynitrite, nitrosative stress, mitochondropathy, encephalomyopathy, CFS, FMS, MCS, lactacidosis, CrP, metabolic syndrome, allergic
umwelt-medizin-gesellschaft 18 (2): 95-106
Autor: Doz. Dr. sc. med. Bodo Kuklinski, Facharzt für Innere Medizin/Umweltmedizin, Vorsitzender des wissenschaftlichen Beirates der Nährstoff-Akademie Salzburg, Diagnostik- und Therapiezentrum für umweltmedizinischer Erkrankungen, Wielandstr. 7, D-18055 Rostock
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