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Examination of the female Sprague‐Dawley rat as a model of Rosiglitazone (RSG)‐Induced toxicity.
Author(s) -
Herman Eugene,
Knapton Alan,
Miller Terry J,
Espandiari Parvaneh,
Anderson Rayford,
Moore Stacy,
Hanig Joseph
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a234-a
Subject(s) - rosiglitazone , medicine , hemoglobin , hematocrit , toxicity , endocrinology , insulin
Therapy with antidiabetic drugs such as RSG can be limited by cardiovascular and other toxicities. The present study was initiated to develop a model which could be used to identify biomarkers associated with the onset of RSG‐induced cardiovascular toxicity. Groups of 10 week female SD rats (6/group) were treaterd orally with RSG (80 mg/kg), 1% carboxymethylcellulose (CMC) or water daily for 28 days. Animals treated with RSG gained more weight (mean 77 vs 66 or 62 gms) and had significantly lower blood glucose levels (186 vs 214 or 223 mg/dL) than was found in the 2 control groups. As observed in human patients given RSG, values for RBC, hematocrit and hemoglobin concentration were significantly reduced in animals treated with RSG. Serum samples from RSG and CMC‐treated rats analyzed by SELDI using weak cation exchange and immobilized metal affinity Protein Chip[reg]r revealed 11 differentially expressed peaks in the RSG‐treated group not found in the CMC control group. Multivariant analysis demonstrated that principle component evaluation and heirarchial clustering could differentiate RSG from CMC vehicle‐treated rats. Myocyte changes consisting of minimal to moderate degeneration and/or necrosis were noted in the hearts of RSG‐treated animals. Cardiac troponin T levels were not elevated in these animals. RSG also induced diffuse changes in brown (perirenal) as well as multifocal changes in white (peripancreatic and/or periovarian)adipose tissues. These findings suggest that the female SD rat develop certain alterations which have been reported in patients and thus could be an appropriate model to search for potential early biomarkers of RSG‐induced toxicity.