THE EFFECTS OF ETANERCEPT AND CABERGOLINE ON ENDOMETRIOTIC IMPLANTS, UTERUS AND OVARIES IN RAT ENDOMETRIOSIS MODEL.

The pathophysiology of endometriosis is still unknown and treatment options remain controversial. Searches focus on angiogenesis, stem cells, immunologic and inflammatory factors. This study investigated the effects of etanercept and cabergoline on ovaries, ectopic, and eutopic endometrium in an endometriosis rat model. This randomized, placebo-controlled, blinded study included 50 rats, Co(control), Sh(Sham), Cb(cabergoline), E(etanercept), and E + Cb(etanercept + cabergoline) groups. After surgical induction of endometriosis, 2nd operation was performed for endometriotic volume and AMH level. After 15 days of treatment: AMH level, flow cytometry, implant volume, histologic scores, immunohistochemical staining of ectopic, eutopic endometrium, and ovary were evaluated at 3rd operation. All groups had significantly reduced volume, TNF-α, VEGF, and CD 146/PDGF-Rß staining of endometriotic implants comparing to the Sh group (p < 0.05).TNF-α staining of eutopic endometrium in all treatment groups was similar to Sh and Co groups (p > 0.05). E and E + Cb groups significantly decreased TNF-α staining in the ovary comparing to Sh, Co, and Cb groups (p < 0.05). All treatment groups had significantly higher AFC compared to the Sh group. CD25+ Cells' median percentage was significantly increased in the E + Cb group compared to Co, Sh, Cb, and E group. E + Cb group had a significantly higher CD5+ Cells' level than the Co group (p = 0.035). In conclusion; Etanercept and/or Cabergoline decreased volume, TNF-α, VEGF, and CD 146/PDGF-Rß staining of the ectopic endometrial implant. E and E + Cb treatment decreased TNF-α levels in the ovary. E + Cb also increased peripheral blood CD25+ & CD5+ Cell's.

The effect of etanercept on aortic nitric oxide-dependent vasorelaxation in an unpredictable chronic, mild stress model of depression in rats.

Stress has been recognized as a risk factor for cardiovascular disease and depression, but the correlation is not well understood. However, inflammation is known to have a crucial role in both cardiovascular disease and depression. Tumor necrosis factor alpha (TNF-α) is a major cytokine for the activation of neuroendocrine, immune and behavioral responses. Therefore, we aimed to explore the effects of etanercept, an anti-TNF-α fusion protein, on endothelium-dependent vascular reactivity, blood pressure and endothelial nitric oxide synthase (eNOS) immunoreactivity in a model of unpredictable chronic mild stress (UCMS). Male rats were exposed to UCMS for 8 weeks, and etanercept (0.8 mg/kg, weekly) was administered during UCMS induction. The systolic blood pressure was recorded by the tail cuff method, and the relaxant responses of the aorta induced by carbachol, sodium nitroprusside (SNP) and papaverine were evaluated in an isolated organ bath system. UCMS rats exhibited an impaired carbachol-induced relaxant response compared to control rats, but there were no significant differences in the SNP- and papaverine-induced relaxant responses between the control and stressed rats. Etanercept treatment improved the carbachol-induced endothelium dependent relaxations observed in rats that experienced UCMS. No significant change in the systemic blood pressure was observed, but decreased expression of eNOS was detected in the UCMS group. Moreover, there were no significant changes in the etanercept treatment group compared to the control rats. Our results suggest that TNF-α could be a mediator of vascular dysfunction associated with UCMS, which leads to decreased expression of eNOS.