title: Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model.
abstract: Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee (OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated--NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate (CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P < 0.05) compared to NT. There was an increase in CS content in the OA group (77.7 +/- 8.3 microg/mg) compared to sham (53.5 +/- 11.2 microg/mg) (P < 0.05). The CS from OA samples had higher Mw (4:62 +/- 10(4) g/mol) compared to sham (4:18 +/- 0.19 x 10(4) g/mol) (P < 0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 +/- 12.1 microg/mg) and Mw (4:18 +/- 0.2 x 10(4) g/mol) as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.
authors.affiliation: Department of Rheumatology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil. francisco_jr@uol.com.br
authors.forename: Francisco Saraiva
authors.initials: FS
authors.lastname: Silva
authors.forename: Natalino Hajime
authors.initials: NH
authors.lastname: Yoshinari
authors.forename: Rondinelle Ribeiro
authors.initials: RR
authors.lastname: Castro
authors.forename: Virgínia Cláudia Carneiro
authors.initials: VC
authors.lastname: Girão
authors.forename: Margarida Maria Lima
authors.initials: MM
authors.lastname: Pompeu
authors.forename: Judith Pessoa de Andrade
authors.initials: JP
authors.lastname: Feitosa
authors.forename: Francisco Airton Castro
authors.initials: FA
authors.lastname: Rocha
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D018771:Arthralgia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002358:Cartilage, Articular / Q000473:pathology; D002809:Chondroitin Sulfates / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005944:Glucosamine / Q000627:therapeutic use*; D008297:Male; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002809:Chondroitin Sulfates; D005944:Glucosamine
references.citation: Osteoarthritis Cartilage. 2008 Feb;16(2):137-62
references.pmid: 18279766
references.citation: Arthritis Rheum. 2004 Oct;50(10):3145-52
references.pmid: 15476248
references.citation: J Clin Invest. 1966 Jul;45(7):1170-7
references.pmid: 16695915
references.citation: Arch Intern Med. 2002 Oct 14;162(18):2113-23
references.pmid: 12374520
references.citation: Clin Orthop Relat Res. 1993 Mar;(288):40-7
references.pmid: 8458153
references.citation: Arthritis Rheum. 2005 Apr;52(4):1118-28
references.pmid: 15818693
references.citation: Osteoarthritis Cartilage. 2007 Nov;15(11):1318-25
references.pmid: 17543547
references.citation: Cell Mol Life Sci. 2002 Jan;59(1):5-18
references.pmid: 11846033
references.citation: Clin Orthop Relat Res. 2000 Dec;(381):229-40
references.pmid: 11127660
references.citation: Curr Opin Rheumatol. 2006 Sep;18(5):537-47
references.pmid: 16896297
references.citation: Ann Intern Med. 2008 Feb 19;148(4):268-77
references.pmid: 18283204
references.citation: Arthritis Rheum. 2007 Feb;56(2):555-67
references.pmid: 17265490
references.citation: Osteoarthritis Cartilage. 2006 Mar;14(3):250-7
references.pmid: 16300972
references.citation: Osteoarthritis Cartilage. 2006 Aug;14(8):769-76
references.pmid: 16580848
references.citation: Osteoarthritis Cartilage. 2007 Nov;15(11):1256-66
references.pmid: 17561418
references.citation: Lancet. 2001 Jan 27;357(9252):251-6
references.pmid: 11214126
references.citation: Osteoarthritis Cartilage. 2004;12 Suppl A:S69-76
references.pmid: 14698647
references.citation: Osteoarthritis Cartilage. 2006 Jan;14(1):13-29
references.pmid: 16242352
references.citation: Connect Tissue Res. 1982;9(4):247-8
references.pmid: 6215207
references.citation: Cochrane Database Syst Rev. 2005 Apr 18;(2):CD002946
references.pmid: 15846645
references.citation: J Rheumatol. 1991 Mar;18(3):436-46
references.pmid: 1856812
references.citation: J Electromyogr Kinesiol. 1994;4(3):181-92
references.pmid: 20870558
references.citation: Br J Pharmacol. 2004 Jan;141(1):172-82
references.pmid: 14662723
references.citation: Anal Biochem. 1972 Mar;46(1):209-15
references.pmid: 4259625
references.citation: Osteoarthritis Cartilage. 2007 Nov;15(11):1241-8
references.pmid: 17576080
references.citation: J Pharmacol Exp Ther. 2003 Nov;307(2):699-704
references.pmid: 12966152
references.citation: JAMA. 2000 Mar 15;283(11):1469-75
references.pmid: 10732937
references.citation: Arch Intern Med. 2003 Jul 14;163(13):1514-22
references.pmid: 12860572
references.citation: J Rheumatol. 2000 Jan;27(1):205-11
references.pmid: 10648040
references.citation: J Clin Invest. 1992 Dec;90(6):2268-77
references.pmid: 1281828
references.citation: N Engl J Med. 2006 Feb 23;354(8):795-808
references.pmid: 16495392
references.citation: Biochem J. 1978 Jan 1;169(1):143-56
references.pmid: 629741
references.citation: Osteoarthritis Cartilage. 2007 Mar;15(3):354-6
references.pmid: 17208467