title: Chronic treatment with cyclosporine affects systemic purinergic parameters, homocysteine levels and vascular disturbances in rats.
abstract: Vascular disease is a major cause of morbidity and mortality among transplanted recipients and cyclosporine (CsA) treatment has been consistently implicated in this event. In this study we assessed total blood homocysteine levels (tHcy), ecto-nucleotidase activities and adenine nucleotide/nucleoside levels searching for parameters related to the mechanisms of vascular damage induced by chronic CsA treatment in non-transplanted rats. Thirty male Wistar rats were divided in three groups: control group treated with corn oil, CsA 5mg/kg and CsA 15 mg/kg, administered by daily gastric gavage during 8 weeks. CsA 15 mg/kg treatment increased blood levels of tHcy. Both CsA treatments (5mg/kg and 15 mg/kg) decreased adenine nucleotides hydrolysis by ecto-nucleotidases in serum, which negatively correlated with tHcy levels (r: -0.74, r: -0.63 and r: -0.63, p<0.004, for ATP, ADP and AMP, respectively). CsA 15mg/kg induced a statistically significant increase in ADP and decrease in adenosine (ADO) plasma levels compared to control group. THcy levels were positively correlated with plasma ADP levels and negatively correlated with ADO levels (r: 0.84, p<0.0001 and r: -0.68, p<0.0001, respectively). Rats under CsA 15 mg/kg treatment presented cell injury and inflammatory responses in the endothelium and intima layer of the aorta artery. In conclusion, blood ecto-nucleotidases activity, tHcy, and ADP and ADO levels may be implicated in vascular injury induced by CsA treatment.
authors.affiliation: Department of Biochemistry, ICBS, Federal University of Rio Grande do Sul, Avenida Ramiro Barcelos, 2600 Anexo, Porto Alegre 90035-003, RS, Brazil.
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Böhmer
authors.forename: Liz Marina P
authors.initials: LM
authors.lastname: Brum
authors.forename: Débora Guerini
authors.initials: DG
authors.lastname: Souza
authors.forename: André Mendes Ribeiro
authors.initials: AM
authors.lastname: Corrêa
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Oses
authors.forename: Giordano Gubert
authors.initials: GG
authors.lastname: Viola
authors.forename: Paulo Jaconi
authors.initials: PJ
authors.lastname: Saraiva
authors.forename: David
authors.initials: D
authors.lastname: Driemeier
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D006710:Homocysteine / Q000097:blood*; D006868:Hydrolysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000378:metabolism*
chemical_list: D000227:Adenine Nucleotides; D011983:Receptors, Purinergic; D006710:Homocysteine; D016572:Cyclosporine