Effect of colchicine on cyclosporine nephrotoxicity, reduction of TGF-beta overexpression, apoptosis, and oxidative damage: an experimental animal study.
Transplant Proc
; 36(5): 1372-6, 2004 Jun.
Article
em En
| MEDLINE
| ID: mdl-15251335
ABSTRACT
BACKGROUND:
Proinflamatory and profibrotic cytokines may be responsible for the cyclosporine A nephrotoxicity. Increased levels of apoptosis, free oxygen redicals, and transforming growth factor beta (TGF-beta), may play an important roles in the pathogenesis of nephrotoxicity. In this experimental animal study, we sought to investigate the effects of colchicine on the cyclosporine nephrotoxicity.METHOD:
Twenty-four Wistar albino rats were divided into three groups cyclosporine 15 mg/kg subcutaneously (SC); cyclosporine 15 mg/kg SC plus colchicine 30 mcg/kg orally; and a control group; equal doses of olive oil orally were administered to groups 1, 2, and 3. Renal function, cyclosporine levels, and serum malonyldialdehyde (MDA) levels were measured at the end of 4 weeks. Apoptosis, TGF-beta, and other findings were detected in renal tissue with the TUNEL method, with a immunohistochemical method, and with routine staining procedures, respectively.RESULTS:
There were significant differences in the values of mean creatinine clearance between group 1 and group 3 and between group 2 and group 3 (P < .05 for each comparison), but not between group 1 and group 2 (P > .05). MDA levels in group 1 were high compared with the control group (P < .05) with a trend toward elevation relative to group 2 but the results were not statistically significant (P > .05). Renal tubular vacuolization in group 1 and group 2 animal were greater than in the control group, but no significant difference were observed between any of the groups (P > .05). Mononuclear cell infiltration in group 1 and group 2 hosts were higher than the control group, but there was no significant differences between the groups (P > .05). Afferent arteriolar hyalinization was observed group 1 and 2 but not group 3. There was a statistically significant difference between group 1 and group 3 and between group 2 and group 3 (P < .05 for each comparison). The expression level of TGF-beta was higher in group 1 than group 2 or group 3 (P <.05 for each comparison) but group 2 and group 3 were similar (P > .05). Apoptotic cell death count of group 1 was higher than that in group 2 or group 3 (P < .05, for each comparison); moreover, group 2 also showed greater numbers of apoptotic cells than group 3 (P < .001). At the end of the 4 weeks, there was no intersititial fibrosis in any of the hosts.CONCLUSION:
While cyclosporine caused increased TGF-beta expression and apoptotic cell death in the renal tissue of rats colchicine prevented the increase in MDA serum levels, TGF-beta expression, and apoptosis in renal tissue. Our study suggests that colchicine may diminish the cyclosporine nephrotoxicity by its suppressing the expression of TGF-beta, apoptotic cell death, and MDA production.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Colchicina
/
Fator de Crescimento Transformador beta
/
Ciclosporina
/
Apoptose
/
Rim
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transplant Proc
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Turquia