Cyclic 3-hydroxymelatonin: a melatonin metabolite generated as a result of hydroxyl radical scavenging.

Abstract

The pineal secretory product, melatonin, is a potent, endogenous hydroxyl radical (HO.) scavenger. When melatonin was incubated in different in vitro cell-free HO.-generating systems, a novel melatonin adduct was formed. The molecular weight of this new compound is 248. Its structure was found to be cyclic 3-hydroxymelatonin (3-OHM). A proposed reaction pathway suggests that 3-OHM is the footprint product of the interaction between melatonin with HO. 3-OHM was also detected in the urine of both rats and humans. This urinary metabolite is identical to the compound generated in the in vitro chemical reaction between HO. and melatonin. This provides direct evidence that melatonin, under physiological conditions, functions as an antioxidant to detoxify the most reactive and cytotoxic endogenous HO. When exogenous melatonin was administered to young rats, urinary 3-OHM levels increased significantly in the treated rats compared to those in controls. This indicates that even in young animals there is insufficient endogenously produced melatonin to detoxify the basal levels of the toxic HO. The accumulated damage induced by the escaped HO. that results when the HO. avoids detoxification over the course of a life time may directly or indirectly accelerate aging and aging-related diseases.