The effect of melatonin on the Bcl-2 and Bad proteins expression in ovarian corpus luteum cells after exposure to experimental hyperthermia

Abstract

Background. There  is growing interest in  determining the  role of  melatonin in the regulation of proliferation and apoptosis of ovarian cells at various diseases and destabilizing influences. It is believed that the choice between the implementation of  a  cell  death or  survival program determines the  ratio of  anti-apoptotic and pro-apoptotic proteins.The aim. To identify the effect ofmelatonin onthe expression ofanti-apoptotic Bcl-2 and pro-apoptotic Bad and the Bcl-2/Bad ratio in the ovarian luteocytes of Wistar rats in the acute (day 3) and recovery (days 7 and 14) periods after a single exposure to experimental hyperthermia.Methods. Warming up took no  more than 17  minutes. Melatonin was injected subcutaneously (0.1 mg in 0.2 ml of physiological solution) for 3 days after experimental hyperthermia. Comparison groups included rats with physiological solution injection (control) and  animals after experimental hyperthermia + physiological solution injection. The Bad and Bcl-2 expression was determined immunohistochemically on days 3, 7 and 14 after experimental hyperthermia + physiological solution or melatonin injection.Results. On the day 3 after experimental hyperthermia, the effect of the hormone was not detected. A week after experimental hyperthermia + melatonin injection, the Bad expression area decreased more significantly than in rats after experimental hyperthermia + physiological solution injection, which led to an increase in Bcl-2/ Bad ratio. This indicated an increase in anti-apoptotic protection, blocking the development of the internal apoptosis pathway at this time. 2 weeks after experimental hyperthermia + physiological solution injection, the Bcl-2 area decreased more significantly than the Bad area. As a result, the Bcl-2/Bad ratio decreased almost 2-fold compared to the control group. This indicated the activation of the “mitochondrial branch” of luteocyte apoptosis. 2 weeks after experimental hyperthermia + melatonin injection, the Bad and Bcl-2 areas decreased synchronously, which restored Bcl-2/ Bad to control values.Conclusion. The  melatonin injection after experimental hyperthermia shifts the ratio of Bcl-2/Bad expression areas towards an increase in anti-apoptotic Bcl2 already a  week after the  recovery period and  promotes earlier normalization of Bcl-2/Bad to physiological levels (as early as 2 weeks after experimental hyperthermia + melatonin injection).