Ramipril ameliorates endometriosis by inducing oxidative stress-mediated apoptosis in the wistar rat.

Endometriosis is illustrated by the presence of ectopic endometrial cells capable of evading apoptosis outside the uterus. Apoptotic and anti-apoptotic factors in the extra uterine microenvironment can be compromised by the impairment in oxidative status. Angiotensin Converting Enzyme (ACE) Inhibitors and Nitric Oxide (NO) modulators play pivotal role in inflammation, angiogenesis, apoptosis and in abrogating oxidative imbalance. Therefore, in the current study we investigate the role of ACE inhibitor and or NO modulators in mitigating the proliferation of ectopic endometrial lesions in rat model. Sixty adult female virgin wistar rats were utilized; out of which fifteen were used as donor rats and rest forty-two were randomly divided into seven groups after surgical implantation of endometrial explants into rats (group II-VII). Histomorphometric assessment of uteri and ectopic lesions was performed by Hematoxylin and eosin (H-E) staining, followed by immunohistochemical study for Proliferating cell nuclear antigen (PCNA), Bax and Bcl-2. Oxidative stress parameters were evaluated by biochemical estimations, succeeded by immunoblotting of Poly [ADP-ribose] polymerase 1 (PARP1). Additionally, immunoblotting of Vascular endothelial growth factor (VEGF), Bax, Bcl-2 and caspase-3 was also performed. Significant decrease in the diameter of lesions with diffused staining at the extracellular spaces of stromal cells for PCNA accompanied by significant decrease in the expression of VEGF (p < 0.00001) was observed in group III. Furthermore, increased expression of Bax:Bcl-2 ratio (p < 0.001) and cleaved caspase-3 (p ≤ 0.0001) in ectopic lesions of group III was also observed. Administration of ramipril alone results in triggering oxidative stress mediated cleavage of PARP1, augmenting apoptosis in the ectopic lesions.