Coronary Artery Disease And Melatonin: The Mechanisms and Therapeutic Applications.

Background: Delaying the formation of atherosclerosis and reducing cardiac ischemia-reperfusion injury remain pressing issues. Melatonin (MLT) possesses anti-inflammatory and antioxidant properties, rendering it a promising candidate for clinical application in coronary artery disease (CAD) patients. While numerous in vivo experiments have elucidated the regulatory mechanisms of MLT in animal models and clinical trials have preliminarily demonstrated the excellent therapeutic potential of MLT in CAD, several key questions remain unanswered. In this review, the authors elucidate the mechanisms underlying CAD's occurrence, progression, and prognosis; delineate the pathways through which MLT exerts its effects; and present compelling evidence supporting its efficacy in CAD. In addition, the authors also describe unresolved issues in the treatment of CAD with MLT, thus providing scholars with directions for future research.

The effect of manganese on dopamine toxicity and dopamine transporter (DAT) in control and DAT transfected HEK cells.

Chronic exposure to Mn results in the development of a neurological disorder known as manganism characterized by neurological deficits resembling that seen in Parkinsonism. Although dopaminergic neurons within the nigrostriatal pathway appear intact, Mn-induced irregularities in DA transmission have been observed including decreased amphetamine-induced DA release and loss of the dopamine transporter (DAT). Results of studies to evaluate the effect of Mn and DA on cell viability in control and DAT-transfected HEK cells reveal that Mn is equally toxic to both cell lines whereas DA was only toxic to cells containing DAT. DA toxicity was saturable suggesting that transport may be rate limiting. When Mn and DA were added simultaneously to the media, cell toxicity was similar to that produced by Mn alone suggesting that Mn may suppress DA uptake in the DAT containing cells. Preincubation of DA prior to the addition of Mn resulted in cell death which was essentially additive with that produced independently by the two agents. Mn was also shown to decrease DA uptake and amphetamine-induced DA efflux in DAT containing cells. Time-lapsed confocal microscopy indicates that Mn can promote trafficking of cell surface DAT into intracellular compartments which may account for the decrease in DA uptake and DA efflux in these cells. Mn-induced internalization of DAT may provide an explanation for disruption in DA transmission previously reported in the striatum.