Interactions between melatonin and nicotinamide nucleotide: NADH preservation in cells and in cell‐free systems by melatonin

Abstract

Interactions of melatonin and nicotinamide adenine dinucleotide (NADH) have been studied in different experimental models including NADH-promoted oxyhemoglobin oxidation, vanadate-induced NADH oxidation and paraquat-induced NADH depletion in cultured PC12 cells. Our findings indicate that melatonin preserves NADH levels under oxidative stress both in cell-free systems and in cultured PC12 cells. These interactions likely involve electron donation by melatonin and reduction of the NAD radical. As a result, the NAD radical is recycled to NADH and melatonin is oxidized to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK). NADH is a central molecule at the crossroads between energy metabolism and the antioxidant defense system in organisms. Recycling of NADH by melatonin might improve the efficiency of NADH as an energy carrier and as an antioxidant. Interactions between melatonin and NADH may be implicated in mitochondrial metabolism.

Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems

“…In addition to melatonin being the primary synchronizing agent of the circadian sleep pattern, it also acts as a free radical scavenger by modulating expression of antioxidants and decreasing pro-apoptotic proteins, such as Bax [10][11][12][13]. Another use of melatonin as a drug to prevent free radical damage has been widely investigated in infertility treatments [11,12,23,24].…”

“…Another use of melatonin as a drug to prevent free radical damage has been widely investigated in infertility treatments [11,12,23,24].…”

“…Besides melatonin improving disturbed sleep; it acts as a free radical scavenger and affects the redox status of tissues, the association of reactive oxygen species (ROS) with tissue injury under different circumstances may be mitigated with melatonin [11][12][13]. This protective effect of melatonin against free radical damage has been widely analyzed, and it is used for many diseases other than insomnia, including cancer, diabetes, viral infections, and Alzheimer's disease [14][15][16].…”

Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials

“…In the case of ONOO --induced DNA damage, PARP overactivates in a genome-repair process and consumes NAD + as a substrate, causing an energy crisis within cells, leading to their eventual necrosis. Preservation of NAD + and cellular energy production may facilitate PARP to repair the DNA damage rather than blocking PARP; melatonin preserves cellular energy production (96)(97)(98) and protects against DNA damage (99). Under physiologic conditions in resting cells, eNOS-derived NO suppresses both iNOS and cyclooxygenase-2 (COX-2) expression by reducing NF-κB translocation into the nucleus.…”

Melatonin as a stabilizer of mitochondrial function: role in diseases and aging

“…Thus, this could be another mechanism implied in the maintenance of GSH levels, which would prevent in turn both inhibition of C-I by NO and extensive mitochondrial damage produced by hydrogen peroxide (H 2 O 2 ) (Martin et al, 2000a;Phillipson, 2014). Moreover, NAD recycling to NADH by melatonin facilitates ATP OXPHOS production, since NADH acts as a substrate for C-I (Tan et al, 2005;Phillipson, 2014). In summary, as can be noted, the indolamine at mitochondrial level acts as a multifactorial and powerful antioxidant, influencing several components of a complex network that need to be totally clarified.…”