Influence of melatonin on systemic inflammatory status and bone histopathological modifications in female rats with surgically induced menopause

Abstract

Background. Melatonin, N-acetyl-5-methoxy-tryptamine is the major secretion product of the pineal gland with important anti-inflammatory and antioxidant properties, also being an important marker of bone remodelling associated with menopause.

Objectives. The aim of our study was to evaluate the effect of the co-administration of melatonin and estrogen on systemic inflammatory status and bone histopathological modifications in surgically induced menopausal female rats.

Materials and methods. The study was performed on a number of 40 female rats, Wistar breed, which underwent bilateral surgical ovariectomy. Within 14 days postoperative, hormone replacement therapy with estrogen or estrogen with melatonin was initiated, in different doses. The treatment was administered for 12 consecutive weeks. At the end of the treatment we measured the serum levels of IL-6 and TNF-α. The femoral bones were harvested after sacrificing the animals and the thickness of the cortical bones was measured and histologically analysed.

Results. Serum values of inflammatory markers were negatively correlated with melatonin administration, the differences being more important at higher doses of melatonin (for both IL-6 and TNF-α the difference between group E_2M with estrogen substitution and melatonin in double dose and control group W, without hormone replacement, was highly statistically significant with p <0.0001). Bone diameters improved in the case of female rats that received hormone replacement with estrogen and higher dose of melatonin (p = 0.0004 between group E_2M, with hormone replacement and group W, control group).

Conclusions. Melatonin improved inflammatory status and bone histopathological changes in ovariectomized female rats.

Keywords: melatonin, estrogen replacement therapy, inflammation, low bone density