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

@article{Poeggeler1993MelatoninHR,
  title={Melatonin, hydroxyl radical‐mediated oxidative damage, and aging: A hypothesis},
  author={Burkhard Poeggeler and Russel Joseph Reiter and Dun-Xian Tan and Li‐Dun Chen and Lucien C. Manchester},
  journal={Journal of Pineal Research},
  year={1993},
  volume={14}
}
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… 
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References

SHOWING 1-10 OF 126 REFERENCES
Reactive Oxygen Species and the Central Nervous System
TLDR
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
TLDR
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
TLDR
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.
TLDR
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
TLDR
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
TLDR
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.
...
...