Melatonin dosing and time effects on ooferectomized rat endometriosis model

OBJECTIVETo determine and compare the antioxidant and regressive effects of different doses of melatonin on endometrial implants, the distribution of the activity of antioxidant enzyme superoxide dismutase (SOD), angiogenesis factor vascular endothelial growth factor (VEGF) and waste metabolite product of lipid peroxidation malondialdehyde (MDA) in the ooferectomized rat endometriosis model.DESIGNProspective, randomized, controlled experimental studySETTINGExperimental Studies and Research Center of Yeditepe University (YUDETAM).ANIMALSThirtythree, female, nonpregnant, nulligravid Spraque-Dawley albino ratINTERVENTIONSEndometriosis was surgically induced in ooferectomized 33 rats by transplanting an autologous endomyometrial tissue to the highly vascular area on the abdominal peritoneal surface. Estradiol treatment was begun at the first operation and applied until the end of study. Two weeks after the induction operation second look operations were performed and endometriotic lesions evaluated and rats were randomized into three groups: control group and melatonin treatment groups (10 mg/kg/day versus 20 mg/kg/day). After 2 weeks of melatonin treatment third look operations were performed and endometriotic regressions were noted. After these operations melatonin treatment stopped and at the end of the sixth week necropsies were performed to evaluate the rate of recurrence. At all operations endometriotic lesions were biyopsied and nearly 1 ml of peritoneal fluid were collected to study histopathological and biochemical parameters.MAIN OUTCOME MEASURESThe volume and histopathologic scores of endometriotic foci, and levels of superoxide dismutase, vascular endothelial growth factor, and malondialdehyde in the peritoneal fluidRESULTSThe mean volumes of the endometriotic foci were 98.8±17.2 (SEM), 54.1±15,6 (SEM), 42,8±10.5 (SEM) and histopathological scores were 2.2±0.2 (SEM), 2.6±0.2 (SEM), and 2.6±0.1 (SEM) in the 10 mg/kg/day melatonin group at the end of the second, fourth, and sixth weeks.The mean volumes of the endometriotic foci were 108.2±17.5 (SEM), 25.8±3,6 (SEM), 32,7±6,0 (SEM) and histopathological scores were 1.7±0.1 (SEM), 2.2±0.2 (SEM), and 2.7±0.2 (SEM) in the 20 mg/kg/day melatonin group at the end of the second, fourth, and sixth weeks.When the groups were compared, endometriotic volumes were significantly decreased in melatonin treated groups at the 4th and 6th week (p=0.001, p=0.001) and MDA levels were lower at 4th and 6th week in control group than 10 mg/kg/day melatonin group (p=0.004, p=0.03).When the groups were compared;?There was a statistically significant decrease in endometriotic volumes treated with melatonin at 4th and 6th weeks (Group 1 and 2) (p=0.001, p=0.001)?After cessation of melatonin in the 10 mg/kg/day group, SOD activity was significantly decreased (p=0.001).?SOD activities were decreased and MDA levels were increased at 6th week (according to 4th week) significantly in the control group (p=0.02, p=0.02).CONCLUSIONMelatonin treatment resulted in regressed endometriotic lesions in ooferectomized rats. Twenty mg/kg melatonin caused a more pronounced effect than 10 mg/kg/day melatonin did.KEY WORDSEndometriosis, rats, experimental endometriosis models, melatonin