In two recent studies we examine the effect of combining NMN and Melatonin on Ischemia Injury and Cognitive Impariment.
Ischemic heart diseases are the major reasons for disability and mortality in elderly individuals. In this study, we tried to examine the combined effects of nicotinamide mononucleotide (NMN) preconditioning and melatonin postconditioning on cardioprotection and mitochondrial function in ischemia/reperfusion (I/R) injury of aged male rats.
Sixty aged Wistar rats were randomly allocated to 5 groups, including
Isolated hearts were mounted on Langendorff apparatus and then underwent 30-minue ligation of left anterior descending coronary artery to induce regional ischemic insult, followed by 60 minutes of reperfusion.
Nicotinamide mononucleotide (100 mg/kg/d intraperitoneally) was administered for every other day for 28 days before I/R. Melatonin added to perfusion solution, 5 minutes prior to the reperfusion up to 15 minutes early reperfusion.
Myocardial hemodynamic and infarct size (IS) were measured, and the left ventricles samples were obtained to evaluate cardiac mitochondrial function and oxidative stress markers.
Melatonin postconditioning and NMN had significant cardioprotective effects in aged rats; they could improve hemodynamic parameters and reduce IS and lactate dehydrogenase release compared to those of control group.
Moreover, pretreatment with NMN increased the cardioprotection by melatonin.
All treatments reduced oxidative stress and mitochondrial reactive oxygen species (ROS) levels and improved mitochondrial membrane potential and restored NAD+/NADH ratio.
The effects of combined therapy on reduction of mitochondrial ROS and oxidative status and improvement of mitochondrial membrane potential were greater than those of alone treatments. Combination of melatonin and NMN can be a promising strategy to attenuate myocardial I/R damages in aged hearts.
Restoration of mitochondrial function may substantially contribute to this cardioprotection.
Given the fact that both melatonin and nicotinamide mononucleotide (NMN) act as pleiotropic agents (having multiple effects from a single gene) in various age-related cognitive disorders, we aimed to investigate the effect of these compounds separately and together on the cognitive outcomes, mitochondrial function, and apoptosis in aged rats.
Forty old and ten young (24 and 3 months old, respectively) male Wistar rats were randomly allocated into five groups:
Melatonin (10 mg/kg) and NMN (100 mg/kg) were administered, separately or in combination for 28 every other day in aged animals.
The Barnes maze and novel object recognition test were used to assess spatial and episodic-like memories, respectively. Also, apoptosis (form of programmed cell death, or “cellular suicide.”) and alterations in mitochondrial function including reactive oxygen species (ROS) and ATP levels as well as mitochondrial membrane potential were assessed in both prefrontal cortex (PFC) and hippocampus (HIP) regions.
Behavioral results revealed that NMN and melatonin separately or in combination, alleviate aging-induced memory impairment. Moreover, agents’ co-administration declined mitochondrial dysfunction and apoptotic cell count both in PFC and HIP regions. The agents separately or in combination (more potent) could induce neuroprotective effect and improve learning and memory in aged animals.
