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|Title:||Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions|
Menger, Michael D.
Laschke, Matthias W.
|Title:||British Journal of Pharmacology|
|Year of Publication:||2017|
|DDC notations:||610 Medicine and health|
|Publikation type:||Journal Article|
|Abstract:||Background and Purpose Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone. Experimental Approach Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg−1), parecoxib (5 mg·kg−1), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high-resolution ultrasound imaging as well as immunohistochemical and Western blot analyses. Key Results Telmisartan-treated lesions exhibited a significantly reduced lesion volume when compared with vehicle-treated controls and parecoxib-treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67-positive cells and higher numbers of apoptotic cleaved caspase-3-positive stromal cells within the lesions. This was associated with a lower expression of COX-2, MMP-9 and p-Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions. Conclusions and Implications Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis.|
|DOI of the first publication:||10.1111/bph.13874|
|URL of the first publication:||https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.13874|
|Link to this record:||urn:nbn:de:bsz:291--ds-393918|
|Date of registration:||28-Mar-2023|
|Faculty:||M - Medizinische Fakultät|
|Department:||M - Chirurgie|
|Professorship:||M - Prof. Dr. Michael D. Menger|
|Collections:||SciDok - Der Wissenschaftsserver der Universität des Saarlandes|
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