Combined Therapy with Rosiglitazone, Rofecoxib and Celecoxib Enhances Cardiovascular Side Effects through Cytochrome P450 Pathway of Arachidonic Acid Metabolism in Diabetic Arthritis Model Rats
Xuya Zhou1, Ying Liu1, Deqin Xu1, Jie Bao1, Yaru Cao2 and Yong Jin3*
Blood glucose level of control, diabetes and arthritis model rat.
Macroscopic observation on paw swelling of rats. A, Control group rats; B, Model (Adjuvant-induced arthritis) group rats.
Effects of drug-combination on the PGE-2 (A), 20-HETE (B), ET-1 (C) and BNP (D) levels in the experimental groups. Data are the mean ± SD. #P<0.05, ##P<0.01 compare with control group; *P<0.05, **P<0.01 compare with model group.
Effects of drug unification on immunohistochemical. A. Heart tissues. B. Liver tissues. C. Kidney tissues. (1) Control group; (2) diabetes model group; (3) model group of combined disease; (4) rosiglitazone group; (5) rofecoxib group; (6) celecoxib group; (7) treatmented with rosiglitazone and rofecoxib group; (8) treatmented with rosiglitazone and celecoxib group. (Scale bars = 100 um).
Effect of drug combination on the protein of CYP4A1, COX-2 in the experimental groups (A) Kidney. (B) Heart. (C) Liver. Data are the mean ± SD. #P<0.05, ##P<0.01 compare with control group; *P<0.05, **P<0.01 compare with model group.
Proposed mechanism of potential cardiovascular (cvs) side effects of combined therapy with Cox-2 inhibitors and TZDs.