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 im-portant 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 menopau-sal 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 differ-ent 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 sacri-ficing the animals and the thickness of the cortical bones was measured and histologically ana-lysed. Results. Serum values of inflammatory markers were negatively correlated with melatonin ad-ministration, 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 signif-icant 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 inflam-matory status and bone histopathological changes in ovariectomized female rats. Keywords: melatonin, estrogen replacement therapy, inflammation, low bone density