Effect of bazedoxifene on expressions of VEGF, VEGFR2, COX-2 and inflammatory factors in a rat endometriosis model

Rui Hou, Hao Xu, Hui Li
In: Tropical Journal of Pharmaceutical Research · 2021 · vol. 18(9) , pp. 1799–1804 · doi:10.4314/tjpr.v18i9.2 · W3183053220
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Bazedoxifene treatment in a rat endometriosis model reduced vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 2, and cyclooxygenase-2 levels, indicating reduced angiogenesis and inflammation.

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This study investigated the therapeutic potential of bazedoxifene in a rat model of endometriosis by comparing its effects against celecoxib and untreated controls. The researchers administered the drugs intragastrically for twenty-one days and measured levels of vascular endothelial growth factor, soluble vascular endothelial growth factor receptor 2, and cyclooxygenase-2 in serum, peritoneal fluid, and ectopic endometrial tissue. Results indicated that bazedoxifene significantly reduced these pro-angiogenic and inflammatory markers compared to the control group, thereby inhibiting the growth of ectopic endometrium. This paper is centrally about endometriosis — specifically evaluating the molecular mechanisms by which bazedoxifene alleviates angiogenesis and inflammation in an experimental animal model.

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Abstract

Purpose: To study the effect of bazedoxifene on the expressions of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR2), cyclooxygenase synthase 2 (COX-2) and inflammatory factors in a rat endometriosis (EMS) model. Methods: Thirty rats (EMS) were divided into untreated control group, bazedoxifene group and celecoxib group (10 rats per group). Bazedoxifene and celecoxib were administered at doses of 3 and 25 mg/kg, respectively. Negative control rats served as control, and were given 0.9 % sodium chloride at a dose of 10 mL/kg. All treatments were given intragastrically for 21 days. Levels of VEGF, sVEGFR2 and COX-2 in uterine ectopic endometrium were assayed. Results: The levels of VEGF and sVEGFR2 in the serum and peritoneal fluid of the untreated control group were significantly higher than the corresponding control values, while VEGF and sVEGFR2 levels in the serum and peritoneal fluid of the bazedoxifene group were significantly lower than those in the untreated control group (p < 0.05). Bazedoxifene group had lower VEGFR2 and COX-2 levels than untreated control group (p < 0.05). Expression of COX-2 protein in the ectopic endometrium of celecoxib group was significantly lower than that in the untreated control group (p < 0.05). Conclusion: Bazedoxifene alleviates angiogenesis and inflammatory factors in serum and peritoneal fluid of EMS rats, inhibits the expression of sVEGFR2 and COX-2 in ectopic endometrium, and also inhibits the growth of ectopic endometrium. This finding may help to discover additional new drugs.
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Abstract

Purpose: To study the effect of bazedoxifene on the expressions of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor 2 (sVEGFR2), cyclooxygenase synthase 2 (COX-2) and inflammatory factors in a rat endometriosis (EMS) model.

Methods

Thirty rats (EMS) were divided into untreated control group, bazedoxifene group and celecoxib group (10 rats per group). Bazedoxifene and celecoxib were administered at doses of 3 and 25 mg/kg, respectively. Negative control rats served as control, and were given 0.9 % sodium chloride at a dose of 10 mL/kg. All treatments were given intragastrically for 21 days. Levels of VEGF, sVEGFR2 and COX-2 in uterine ectopic endometrium were assayed.

Results

The levels of VEGF and sVEGFR2 in the serum and peritoneal fluid of the untreated control group were significantly higher than the corresponding control values, while VEGF and sVEGFR2 levels in the serum and peritoneal fluid of the bazedoxifene group were significantly lower than those in the untreated control group (p < 0.05). Bazedoxifene group had lower VEGFR2 and COX-2 levels than untreated control group (p < 0.05). Expression of COX-2 protein in the ectopic endometrium of celecoxib group was significantly lower than that in the untreated control group (p < 0.05).

Conclusion

Bazedoxifene alleviates angiogenesis and inflammatory factors in serum and peritoneal fluid of EMS rats, inhibits the expression of sVEGFR2 and COX-2 in ectopic endometrium, and also inhibits the growth of ectopic endometrium. This finding may help to discover additional new drugs.

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endometriosis

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