The effects of different doses of melatonin treatment on endometrial implants in an oophorectomized rat endometriosis model

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Melatonin treatment, at 10 and 20 mg/kg/day, decreased endometriotic foci volumes in oophorectomized rats, with lower MDA levels observed in the control group compared to the 10-mg/kg/day group.

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This experimental study used surgically induced endometriosis in oophorectomized Sprague–Dawley rats, assigning animals to receive melatonin at 10 mg/kg/day, 20 mg/kg/day, or a control condition while estradiol was administered after the first operation; endometriotic lesion size, histology, and biochemical markers (SOD, VEGF, and MDA) were assessed at second, fourth, and sixth weeks. Melatonin exposure was associated with significant regression of endometriotic foci volumes in both melatonin groups versus control at weeks 4 and 6, while histopathological scores were not significantly different between melatonin and control and SOD and VEGF levels did not differ between groups. A caveat highlighted by the results is that MDA was significantly lower in the control group than in the 10 mg/kg/day melatonin group at later time points, indicating non-uniform effects on lipid peroxidation across doses. This paper is centrally about endometriosis — it tests dose-dependent melatonin effects on regression of endometrial implants and associated oxidative stress and angiogenesis markers in an oophorectomized rat endometriosis model.

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Abstract

Aims To determine the effects of different doses of melatonin treatment on endometrial implants, the activity of antioxidant enzyme superoxide dismutase (SOD), the angiogenesis factor, the vascular endothelial growth factor (VEGF) and the waste metabolite product of lipid peroxidation malondialdehyde (MDA) in an oophorectomized rat endometriosis model.

Methods

Thirty-two, female, non-pregnant, nulligravid Sprague–Dawley, albino rats were used in this prospective, randomized, controlled and experimental study. Endometriosis was surgically induced in oophorectomized rats, and estradiol treatment was started after the first operation and continued till the end of the study. Second look, third look and necropsy operations were performed in the 2nd, 4th and 6th weeks. Mean volumes, histological scores and biochemical parameters were evaluated throughout the study.

Results

The mean volumes of endometriotic foci were 98.8 mm3 ± 17.2 vs. 108.2 mm3 ± 17.5, 54.1 mm3 ± 15.6 vs. 25.8 mm3 ± 3.6, 42.8 mm3 ± 10.5 vs. 32.7 mm3 ± 6.0 and histopathological scores were 2.2 ± 0.2 vs. 1.7 ± 0.1, 2.6 ± 0.2 vs. 2.2 ± 0.2, 2.6 ± 0.1 vs. 2.7 ± 0.2 in the 10 vs. 20-mg/kg/day melatonin group at the end of the second, fourth and sixth weeks, respectively. When the groups were compared, no significant differences were seen in the histopathologic scores, SOD and VEGF levels between the groups. However, the endometriotic foci volumes were significantly decreased in both melatonin treatment groups with respect to the control group at the end of the fourth and sixth weeks. Moreover, the mean MDA levels were significantly lower in the control group than in the 10-mg/kg/day melatonin group at the end of the fourth and sixth weeks.

Conclusion

Melatonin treatment resulted in the regression of endometriotic lesions in oophorectomized rats. Higher doses of melatonin treatment might be more effective in the regression of implants and improvement of histologic scores as well as in the precise evaluation of SOD, MDA and VEGF distributions in the rat experimental models. Similar content being viewed by others

References

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Antioxidants Endometriosis Melatonin Vascular Endothelial Growth Factor A Animals Antioxidants Antioxidants Dose-Response Relationship, Drug Endometriosis Endometriosis Endometriosis Female Humans Lipid Peroxidation Lipid Peroxidation Malondialdehyde Malondialdehyde Melatonin Melatonin Ovariectomy

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