The effect of bevacizumab (Anti-VEGF) on volumes and histopathological scores of endometriotic lesions and VEGF levels in peritoneal fluid and tissue samples in the experimental rat endometriosis model

The Effect Of Bevacizumab (Anti-VEGF) on Volumes and Histopathological Scores of Endometriotic Lesions and VEGF Levels in Peritoneal Fluid and Tissue Samples in The Experimental Rat Endometriosis Model Objective: To investigate the effect of Bevacizumab, which is one of the anti-VEGF agents, on surgically created endometriotic foci volume, histopathologic scores and VEGF levels in the peritonel fluid and tissue samples in the rat endometriosis model. Materials and Methods: Sixteen Sprague-Dawley albino rats were used in the experiment. Each of them has undergone four operations. Four endometriotic foci induction with homologous uterine horn autotransplantation was performed in the first operation. High doses of estrogen twice a week (50 mg / kg) was given subcutaneously to create the endometriotic foci after the surgical induction. After fourteen days (two weeks) the second operation was performed and the endometriotic foci were examined. One of the endometriotic foci was excised. Peritoneal fluid cytology was taken. After the second operation the rats were randomised in to two groups. The first group was administered 5 mg/kg Bevacizumab in every 3 days for 21 days (3 weeks) until the third operation. The control group had no medication for 3 weeks. The purpose of the third operation was to evaluate the therapeutic effect of Bevacizumab in the endometriotic foci. Following this operation the treatment has ceased and the rats were observed under estrogen administration for 21 days. The rats were sacrified under general anestesia (necropsy, fourth operation) and recurrence status was compared with the control group. Results: None of the rats were lost and no toxic drug effects were seen in rats during experiment. The average volume of lesions in the bevacizumab group and its terms were evaluated according to the period, before treatment the mean volume was 122.6 ± 24.4 mm3and after bevacizumab treatment was calculated as 20.6 ± 6.3 mm3. Likewise, the mean volume during recurrences were recorded as 10.4 ± 5.2 mm3 (p = 0.001).Histopathological lesions in the bevacizumab group and their scores were evaluated according to terms of the period, while pre-treatment and post-treatment scores were2.8 ± 0.1, 2.3 ± 0.1 subsequently, 0.5 ± 0.3 was calculated at recurrence time (p = 0.01). No difference was observed in the avarege volumes and histopathological scores in the control group. In the bevacizumab group before the treatment the VEGF level was 4.8±1.2 pg/ml in the peritoneal fluid. It was found 18.6±4.7 pg/ml after the treatment (p=0.02). Before the treatment the avarage VEGF level in the tissue was calculated 47.0±5.1 pg/ml, this level in the post-treatment period was calculated as 34.5 ± 4.1 (p=0.03). No significant differences were found in VEGF leves of the control group. Discussion: The pathophysiology of endometriosis remains unclear.Whatever the underlying pathophysiological mechanisms, angiogenesis assumes the key role in the development of endometriotic lesions. Angiogenesis is a complex condition that includes the formation of new blood vessels originating from an existing vessel. VEGF is a potent angiogenic factor which increases endometriosis. Bevacizumab is a recombinant human monoclonal antibody that inhibits VEGF. In our study the volumes and the scores were observed significantly decreased in the bevacizumab group especially in the recurrence period. Result: Endometriosis doesn't have a definitive therapy. Both following surgical and medical therapies, high recurrence rate is observed. Potent anti-angiogenic drugs such as bevacizumab for the prevention of relapse may open new horizons. Key words: Endometriosis, Rat, VEGF, Anti-VEGF, Bevacizumab