Treatment with melatonin induces a reduction of Toxoplasma gondii development in LLC-MK2 cells.

Abstract

It is known that the current treatment for toxoplasmosis causes side effects. Thus, it is essential to develop new therapies with reduced adverse effects while concurrently maintaining broad coverage and prophylactic therapy. Melatonin is a hormone that participates in the circadian cycle in vertebrates and has antioxidant, immunomodulatory, and antitumoral functions. In addition, it has been shown that melatonin can modulate immune responses and parasitic development during infection by Trypanosoma cruzi and Leishmania spp. Furthermore, studies indicate that melatonin increases the number of lymphocytes in rats infected by Toxoplasma gondii. However, there is no information on the possible effects of melatonin in T. gondii-infected host cells in vitro. This study analyzed the effects of melatonin treatment in the monkey kidney cell epithelial cell line, LLC-MK2, after infection with T. gondii. LLC-MK2 cells were infected and treated/not treated with melatonin, and the infection index was then quantified. Melatonin treatment did not alter host cell viability and was able to reduce parasite proliferation in LLC-MK2 cells at 24 and 48h and at 6days. Analysis by scanning electron microscopy confirmed reduction of parasite proliferation and alterations of tachyzoite shapes. Transmission electron microscopy images showed parasites with ruptured plasma membranes and cytoplasmic leakage. After treatment, parasites showed positive staining for apoptotic-like cell death. These results suggest that the use of melatonin as the lead compound for the synthesis of new compounds may constitute an alternative treatment for toxoplasmosis.