ND: |
ME10608273 |
PMID: |
10608273 |
LR: |
20051117 |
CED: |
20000106 |
DCO: |
20000106 |
Autoren: |
McCarty MF; Russell AL |
Titel: |
Niacinamide therapy for osteoarthritis--does it inhibit nitric oxide synthase induction by interleukin 1 in chondrocytes? |
Quelle: |
Medical hypotheses; VOL: 53 (4); p. 350-60 /199910/ |
PM: |
Print |
SU: |
IM |
Sprache: |
English |
CY: |
ENGLAND |
JID: |
7505668 |
ISSN: |
0306-9877 |
CO: |
MEHYDY |
Institution: |
Nutrition 21/AMBI, San Diego, CA 92037, USA. |
DT: |
Journal Article |
Schlagwörter |
CT: |
ANTIOXIDANTS/pharmacology; CARTILAGE, ARTICULAR/drug effects; CARTILAGE, ARTICULAR/enzymology; CARTILAGE, ARTICULAR/*metabolism; ENZYME INHIBITORS/*therapeutic use; FISH OILS/pharmacology; GLUCOSAMINE/pharmacology; HUMANS; HYALURONIC ACID/pharmacology; INTERLEUKIN-1/antagonists & inhibitors; INTERLEUKIN-1/*physiology; NIACINAMIDE/*therapeutic use; NITRIC OXIDE SYNTHASE/*antagonists & inhibitors; NITRIC OXIDE SYNTHASE/biosynthesis; OSTEOARTHRITIS/*drug therapy; S-ADENOSYLMETHIONINE/pharmacology; SIGNAL TRANSDUCTION |
CTG: |
ANTIOXYDANZIEN/Pharmakologie; KNORPEL, GELENK-/Arzneimittelwirkungen; KNORPEL, GELENK-/Enzymologie; KNORPEL, GELENK-/*Stoffwechsel; ENZYMINHIBITOREN/*therapeutische Anwendung; FISCHÖLE/Pharmakologie; GLUCOSAMIN/Pharmakologie; MENSCH; HYALURONSÄURE/Pharmakologie; INTERLEUKIN-1/Antagonisten & Inhibitoren; INTERLEUKIN-1/*Physiologie; NIACINAMID/*therapeutische Anwendung; STICKSTOFFMONOXID-SYNTHASE/*Antagonisten & Inhibitoren; STICKSTOFFMONOXID-SYNTHASE/Biosynthese; OSTEOARTHROSE/*Arzneimitteltherapie; S-ADENOSYLMETHIONIN/Pharmakologie; SIGNALÜBERTRAGUNG |
TE: |
Antioxidants; Enzyme Inhibitors; Fish Oils; Interleukin-1; S-Adenosylmethionine/29908-03-0; Glucosamine/3416-24-8; Hyaluronic Acid/9004-61-9; Niacinamide/98-92-0; Nitric Oxide Synthase/E.C. 1.14.13.39 |
CR: |
29908-03-0; 3416-24-8; 9004-61-9; 98-92-0; E.C. 1.14.13.39 |
AB: |
Fifty years ago, Kaufman reported that high-dose niacinamide was beneficial in osteoarthritis (OA) and rheumatoid arthritis. A recent double-blind study confirms the efficacy of niacinamide in OA. It may be feasible to interpret this finding in the context of evidence that synovium-generated interleukin-1 (IL-1), by inducing nitric oxide (NO) synthase and thereby inhibiting chondrocyte synthesis of aggrecan and type II collagen, is crucial to the pathogenesis of OA. Niacinamide and other inhibitors of ADP-ribosylation have been shown to suppress cytokine-mediated induction of NO synthase in a number of types of cells; it is therefore reasonable to speculate that niacinamide will have a comparable effect in IL-1-exposed chondrocytes, blunting the anti-anabolic impact of IL-1. The chondroprotective antibiotic doxycycline may have a similar mechanism of action. Other nutrients reported to be useful in OA may likewise intervene in the activity or synthesis of IL-1. Supplemental glucosamine can be expected to stimulate synovial synthesis of hyaluronic acid; hyaluronic acid suppresses the anti-catabolic effect of IL-1 in chondrocyte cell cultures, and has documented therapeutic efficacy when injected intra-articularly. S-adenosylmethionine (SAM), another proven therapy for OA, upregulates the proteoglycan synthesis of chondrocytes, perhaps because it functions physiologically as a signal of sulfur availability. IL-1 is likely to decrease SAM levels in chondrocytes; supplemental SAM may compensate for this deficit. Adequate selenium nutrition may down-regulate cytokine signaling, and ample intakes of fish oil can be expected to decrease synovial IL-1 production; these nutrients should receive further evaluation in OA. These considerations suggest that non-toxic nutritional regimens, by intervening at multiple points in the signal transduction pathways that promote the synthesis and mediate the activity of IL-1, may provide a substantially superior alternative to NSAIDs (merely palliative and often dangerously toxic) in the treatment and perhaps prevention of OA. |