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Combined Therapy with Rosiglitazone, Rofecoxib and Celecoxib Enhances Cardiovascular Side Effects through Cytochrome P450 Pathway of Arachidonic Acid Metabolism in Diabetic Arthritis Model Rats

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*

1Department of Pharmacy, Hospital of Armed Police of Anhui Province, Hefei 230061, China
2Department of Pharmacy, The Fourth People Hospital of Wuhu, Wuhu 24000,China
3School of Pharmacy, Anhui Medical University, Hefei 230032, China
 
Xuya Zhou and Ying Liu contributed equally to this work and should be considered co-first authors.


*      Corresponding author: jinyong@ahmu.edu.cn 

Fig. 1.

Blood glucose level of control, diabetes and arthritis model rat.

Fig. 2.

Macroscopic observation on paw swelling of rats. A, Control group rats; B, Model (Adjuvant-induced arthritis) group rats.

Fig. 3.

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.

Fig. 4.

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).

Fig. 5.

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.

Fig. 6.

Proposed mechanism of potential cardiovascular (cvs) side effects of combined therapy with Cox-2 inhibitors and TZDs.

Pakistan Journal of Zoology

February

Vol. 53, Iss. 1, Pages 1-400

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