Colchicine decreases apoptotic cell death in chronic cyclosporine nephrotoxicity

• Published in: The Journal of laboratory and clinical medicine 2002-06, Vol.139 (6), p.364-371
• Main Authors: Li, Can, Yang, Chul Woo, Ahn, Hee Jong, Kim, Wan Young, Park, Cheol Whee, Park, Joo Hyun, Lee, Myung Ja, Yang, Ji Hye, Kim, Yong-Soo, Bang, Byung Kee
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; bcl-2-Associated X Protein; Biological and medical sciences; Caspase 3; Caspases - metabolism; Colchicine - therapeutic use; Cyclosporine - blood; Cyclosporine - toxicity; Drug toxicity and drugs side effects treatment; Immunosuppressive Agents - blood; Immunosuppressive Agents - toxicity; In Situ Nick-End Labeling; Kidney - chemistry; Kidney Diseases - chemically induced; Kidney Diseases - drug therapy; Kidney Diseases - pathology; Male; Medical sciences; Nephritis, Interstitial - chemically induced; Nephritis, Interstitial - drug therapy; Nephritis, Interstitial - pathology; Pharmacology. Drug treatments; Proto-Oncogene Proteins - analysis; Proto-Oncogene Proteins c-bcl-2 - analysis; Rats; Rats, Sprague-Dawley; Toxicity: urogenital system
• ISSN: 0022-2143; 1532-6543
• DOI: 10.1067/mlc.2002.124397

Colchicine has been shown to prevent kidney injury in chronic cyclosporine nephrotoxicity; however, the mechanisms of its action are undetermined. The purpose of this study was to clarify whether colchicine prevents cyclosporine-induced kidney injury by decreasing kidney-cell apoptosis. We also sought to determine whether such an antiapoptotic effect was related to Bcl-2/Bax protein and caspase3 activity. Adult male Sprague-Dawley rats kept on a salt-depleted diet (0.05% sodium) were treated daily for 28 days with cyclosporine (15 mg/kg in 1 mL/kg olive-oil vehicle), colchicine (30 μg/kg in 100% ethanol, diluted with sterile saline solution to a final concentration of 30 μg/mL), or both cyclosporine and colchicine. Kidney function, histomorphologic findings, in situ terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick end-labeling assay, expressions of Bcl-2 and Bax proteins, and caspase-3 enzymatic activity were compared for the different treatment groups. Compared with the vehicle-treated rats, rats given cyclosporine showed a decline in creatinine clearance rate, an increase in serum creatinine concentration, tubulointerstitial fibrosis, and an increase in the number of apoptotic cells (all P