Colchicine vs. omega-3 fatty acids for prevention of chronic cyclosporine nephrotoxicity in Sprague Dawley rats: an experimental animal model.
BACKGROUND
In view of the high cost of the new immunosuppressive drugs, which represents a challenge for both patients and governmental resources especially in developing countries, trials to prevent side effects of the first calcineurin inhibitor discovered (cyclosporine, Cs) are of particular interest.


METHODS
In this prospective randomized experimental study, 60 male Sprague Dawley rats were enrolled. Group 1 served as negative control group and received olive oil. Group 2 received Cs orally 100 mg/kg for 80 days and served as positive control group. Group 3 was given daily colchicine (30 microg/kg/day) in addition to Cs. Group 4 was given omega-3 fatty acids (100 mg/kg/day) in addition to Cs. Animals were subjected every other week to laboratory assessment for serum creatinine, sodium, potassium, and Cs whole-blood through levels. At the end point, the animals were sacrificed, and kidney tissue was examined for histopathological changes.


RESULTS
There were no significant differences in serum creatinine, creatinine clearance, and serum sodium and potassium in all groups. Histopathological examination of kidney tissues showed focal tubular atrophy and interstitial fibrosis in inner medulla and inner strip of the outer medulla in all Cs-treated animals. Morphological changes were significantly less in colchicine-treated rats compared to omega-3 fatty acid-treated rats and absent in the negative control group. Furthermore, immunostaining showed positive reactions for vimentin in Cs-treated animals only.


CONCLUSIONS
Colchicine and omega-3 fatty acids are protective for the kidney against cyclosporine-induced nephropathy; however, colchicine is more protective than omega-3 fatty acid.
Sabry
Alaa
A
Nephrology and Internal Medicine Department, Mansoura Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. asabry20@yahoo.com <asabry20@yahoo.com>
El-Husseini
Amr
A
Sheashaa
Hussien
H
Abdel-Shafy
Eid
E
El-Dahshan
Khaled
K
Abdel-Rahim
Mona
M
Abdel-Kaleek
Ehab
E
Abo-Zena
Hamdy
H
D000818:Animals; D003078:Colchicine / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000737:chemistry / Q000473:pathology; D008297:Male; D011188:Potassium / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D012964:Sodium / Q000097:blood; D050257:Tubulin Modulators / Q000627:therapeutic use*; D014746:Vimentin / Q000032:analysis
D015525:Fatty Acids, Omega-3; D007166:Immunosuppressive Agents; D050257:Tubulin Modulators; D014746:Vimentin; D016572:Cyclosporine; D012964:Sodium; D003404:Creatinine; D011188:Potassium; D003078:Colchicine