Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis

  title={Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis},
  author={Burkhard Poeggeler and Russel Joseph Reiter and Dun-Xian Tan and Lidun Chen and Lucien C. Manchester},
  journal={Journal of Pineal Research},
Abstract: Melatonin is a very potent and efficient endogenous radical scavenger. The pineal indolamine reacts with the highly toxic hydroxyl radical and provides on‐site protection against oxidative damage to biomolecules within every cellular compartment. Melatonin acts as a primary non‐enzymatic antioxidative defense against the devastating actions of the extremely reactive hydroxyl radical. Melatonin and structurally related tryptophan metabolites are evolutionary conservative molecules… 

Melatonin: a well‐documented antioxidant with conditional pro‐oxidant actions

Although the vast majority of studies proved the antioxidant capacity of melatonin and its derivatives, a few studies using cultured cells found that melatonin promoted the generation of ROS at pharmacological concentrations in several tumor and nontumor cells; thus, melatonin functioned as a conditional pro‐oxidant.

Oxidative damage in the central nervous system: protection by melatonin

Oxidative processes and antioxidative defense mechanisms in the aging brain 1

  • R. Reiter
  • Biology
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 1995
A newly discovered, potentially highly important antioxidant in the brain is the indole melatonin, which is more effective than glutathione in scavenging the highly toxic hydroxyl radical and also more efficient than vitamin E in neutralizing the peroxyl radical.

Melatonin Reduces Oxidant Damage and Promotes Mitochondrial Respiration

Recent observations documenting melatonin's ability to stimulate electron transport and ATP production in the inner‐mitochondrial membrane also has relevance for melatonin as an agent that could alter processes of aging.

Significance of Melatonin in Antioxidative Defense System: Reactions and Products

Melatonin in plants not only provides an alternative exogenous source of melatonin for herbivores but also suggests that melatonin may be an important antioxidant in plants which protects them from a hostile environment that includes extreme heat, cold and pollution, all of which generate free radicals.

Oxygen radical detoxification processes during aging:The functional importance of melatonin

Experimental results from a variety of sources provide evidence that melatonin is operative in the cell nucleus, in the aqueous cytosol and in lipid- rich cellular membranes as an antioxidant.

Aging and oxygen toxicity: Relation to changes in melatonin

Besides its ability to abate oxidative damage, other beneficial features of melatonin may be important in combating the signs of aging; these include melatonin’s immune-stimulating function, its sleep-promoting ability, its function as an anti-viral agent, and general protective actions at the cellular level.

The pineal secretory product melatonin reduces hydrogen peroxide‐induced DNA damage in U‐937 cells

It is suggested that melatonin, an endogenous antioxidant and nontoxic compound, may have an important role in protecting cells from genetic damage due to free radicals, supporting the idea of this hormone as a possible therapeutic agent in preventing aging and age‐related diseases.

Reactive Oxygen Species and the Central Nervous System

The nature of antioxidants is discussed, it being suggested that antioxidant enzymes and chelators of transition metal ions may be more generally useful protective agents than chain‐breaking antioxidants.

Hydroxyl radical production and lipid peroxidation paralles selective post‐ischemic vulnerability in gerbil brain

It is hypothesized that the selective ischemic vulnerability of the hippocampus is mechanistically related to a selective post‐ischemic burst in ·OH in that region, and this may be based upon an intrinsically higher level of oxidative stress in that area as a by‐product of greater arachidonic acid turnover.

Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage

It appears that during ischemic states, brain production of reactive molecules (free radicals) causes an increased output of EAA, which may trigger a series of events which could help to explain the delayed loss of neurons after a transient isChemic period.

Antioxidative properties of harmane and beta-carboline alkaloids.

Harmane and related compounds exhibited concentration-dependent inhibition of lipid peroxidation in a hepatic microsomal preparation incubated with either enzymatic dependent (Fe3+ ADP/NADPH) or non-enzymatic based oxygen radical producing systems, suggesting that beta-carbolines may also serve as endogenous antioxidants.

Peroxide-producing potential of tissues: inverse correlation with longevity of mammalian species.

  • R. Cutler
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1985
Kinetic analysis of the data indicates that the amount of peroxidizable substrate was the major factor determining the rate of autoxidation, and the hypothesis that aging may be caused in part by oxygen radicals initiating peroxidation reactions is supported.

Mechanism of Kainate Toxicity to Cerebellar Neurons In Vitro Is Analogous to Reperfusion Tissue Injury

It is reported here that kainate‐induced death of cerebellar neurons in culture is prevented by inhibiting the enzyme xanthine ox‐idase, a cellular source of cytotoxic superoxide radicals (O2‐), which indicates that excitotoxin‐induced neuronal degeneration is mediated bysuperoxide radicals generated by x anthine oxidase.