Rosiglitazone protects against cyclosporine-induced pancreatic and renal injury in rats.
Rosiglitazone (RGTZ) has protective effect against various types of injury. This study was performed to evaluate the effect of RGTZ on pancreatic and renal injury caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered alone and together to the rats for 28 days. The effect of RGTZ on CsA-induced pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT), plasma insulin concentrations and pancreatic beta-cell morphology. The effect of RGTZ on CsA-induced renal injury was evaluated by assessing renal function and pathology; mediators of inflammation and fibrosis such as angiotensin II (AngII), osteopontin (OPN) and transforming growth factor-beta1 (TGF-beta1) and apoptotic cell death. Four weeks of CsA treatment caused diabetes, renal dysfunction, typical pathologic lesions (arteriolopathy, interstitial fibrosis and inflammatory cells infiltration) and apoptotic cell death. RGTZ treatment decreased blood glucose concentration, increased plasma insulin concentration and preserved pancreatic beta islet mass. RGTZ treatment improved renal function and histopathology. Pro-inflammatory and pro-fibrotic molecules such as AngII, OPN and TGF-beta1, and apoptotic cell death also decreased with RGTZ treatment. These data suggest that RGTZ has a protective effect against CsA-induced pancreatic and renal injury.
Chung
Byung Ha
BH
Xenotransplantation Center, Department of Internal Medicine, The Catholic University of Korea, Seoul, South Korea.
Li
Can
C
Sun
Bo Kyung
BK
Lim
Sun Woo
SW
Ahn
Kyung Ohk
KO
Yang
Ji Hun
JH
Choi
Yoon Hee
YH
Yoon
Kun Ho
KH
Sugawara
Akira
A
Ito
Sadayoshi
S
Kim
Jin
J
Yang
Chul Woo
CW
D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D016572:Cyclosporine / Q000097:blood / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000097:blood / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D053495:Osteopontin; D010182:Pancreatic Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1
D007004:Hypoglycemic Agents; D007166:Immunosuppressive Agents; D007328:Insulin; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; C508962:Tgfb1 protein, rat; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077154:Rosiglitazone; D053495:Osteopontin; D000804:Angiotensin II; D016572:Cyclosporine