Tranilast attenuates chronic cyclosporine nephrotoxicity in rats.
Our aim was to explore the effects of the anti-allergic and antifibrotic agent tranilast on chronic cyclosporine (CsA) nephrotoxicity in rats.


METHODS
Eighteen Sprague-Dawley rats were randomized to be given the following daily treatments by gavage for 4 weeks: (1) controls, olive oil; (2) CsA group, CsA 25 mg/kg; (3) CsA plus tranilast group, CsA 25 mg/kg and tranilast 400 mg/kg. We examined the body weights and the effects of tranilast on histopathology, macrophage (Mvarphi) infiltration, and expression of osteopontin (OPN).


RESULTS
The administration of tranilast improved body weight gain by CsA-treated rats (232 +/- 24 vs 203 +/- 6 g; P < .05). This treatment reduced the expression of OPN protein and infiltration of macrophages (9.14 +/- 2.7 vs 22.44 +/- 5.68 ED-1 positive cells per high power field, P < .05). Furthermore compared with the CsA alone group, it ameliorated tubulointerstitial fibrosis scores (1.18 +/- 0.08 vs 2.57 +/- 0.21, P < .05).


CONCLUSIONS
Tranilast attenuated tubulointerstitial fibrosis through decreased expression of OPN protein and macrophage infiltration, showing renal protective effects in rats with chronic CsA nephrotoxicity.
Tao
Y
Y
Department of Nephrology, West China Hospital; Department of Immunology, College of Pre-clinical and Forensic Medicine, West China Center of Medical Sciences, Sichuan University, China.
Hu
L
L
Li
S
S
Bai
Y
Y
Liu
Q
Q
Jin
Y
Y
Wei
D
D
Luo
Z
Z
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016572:Cyclosporine / Q000633:toxicity*; D005355:Fibrosis / Q000473:pathology* / Q000517:prevention & control; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000737:chemistry / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D062367:ortho-Aminobenzoates; D016572:Cyclosporine; C012293:tranilast