L-arginine prevents bone loss and bone collagen breakdown in cyclosporin A-treated rats.
Cyclosporin A is implicated in the pathogenesis of post-transplantation bone disease. Because of recent evidence that cyclosporin A may cause renal and cardiovascular toxicity by inhibiting nitric oxide (NO) activity, and that NO slows bone remodeling and bone loss in animal and human studies, we investigated a possible link between NO production and beneficial effects on bone health in cyclosporin A-treated rats. Thirty-six 10-week-old male rats were assigned to six groups of six animals each, and treated for 4 weeks with: vehicle; cyclosporin A; L-arginine; N(G)-nitro-L-arginine methylester (L-NAME, a general inhibitor of NO synthase activity); a combination of cyclosporin A+L-arginine; and a combination of cyclosporin A+L-NAME. Whole body and regional (spine and pelvis) bone mineral content of rats were measured under basal conditions and at the end of the treatment period by dual-energy X-ray absorptiometry (DXA) scanning. Femur weights and serum concentrations of pyridinoline, a reliable marker of bone resorption, were measured at the end of the study period. Cyclosporin A-, L-NAME-, and cyclosporin A+L-NAME-treated rats had significantly lower bone mineral content and femur weights, and significantly higher pyridinoline levels than did control animals. The administration of L-arginine appeared to prevent bone loss caused by cyclosporin A, suggesting that this amino acid, which can be converted to produce NO, might prove useful in preventing disturbed bone modeling and inhibition of bone growth associated with cyclosporin A therapy.
Fiore
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CE
Department of Internal Medicine, University of Catania O.V.E., Via Plebiscito 628, 95124, Catania, Italy. carmelo.fiore@tin.it
Pennisi
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P
Cutuli
V M
VM
Prato
A
A
Messina
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R
Clementi
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G
D000596:Amino Acids / Q000097:blood / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; C015484:pyridinoline; D016572:Cyclosporine; D003094:Collagen; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester