Melatonin and 6-hydroxymelatonin protect against iron-induced neurotoxicity.

Oxidative damage of biological macromolecules is a hallmark of most neurodegenerative disorders such as Alzheimer, Parkinson and diffuse Lewy body diseases. Another important phenomenon involved in these disorders is the alteration of iron homeostasis, with an increase in iron levels. The present study investigated whether 6-hydroxymelatonin (6-OHM) can reduce Fe2+-induced lipid peroxidation and necrotic cell damage in the rat hippocampus in vivo. It was found that 6-OHM administration proved successful in reducing Fe2+-induced neurotoxicity in rat hippocampus. This study provides some evidence of the neuroprotective effects of 6-OHM.

l-DOPA administration enhances 6-hydroxydopamine generation.

The therapeutic success of L-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease (PD) patients remains controversial as many patients become tolerant requiring higher dosage regimens. However, the increase in dosage regimens results in the patients experiencing intolerable side effects. This study sought to investigate whether dopamine (DA) can chemically react with iron to form the potent neurotoxin 6-hydroxydopamine (6-OHDA). Furthermore, rats were treated with L-DOPA for a period of 7 and 28 days to determine whether L-DOPA treatment results in 6-OHDA formation in rat striatum. In addition, this study also investigates the complex interactions of L-DOPA with iron by performing in vitro and in vivo lipid peroxidation studies and the detection of endogenous 6-OHDA in iron-infused rats. In each study, melatonin was used to determine whether it could quench any free radical effects that may occur. The results of the present study show that DA chemically reacts with iron to form 6-OHDA. Moreover, L-DOPA treatment results in endogenous 6-OHDA formation in rat brain as well as enhances iron-induced lipid peroxidation both in vitro and in vivo in the rat striatum. The L-DOPA-induced increase in lipid peroxidation, in iron-infused rats, corresponds with an increase in levels of 6-OHDA in the rat striatum. The use of melatonin significantly decreases the L-DOPA-stimulated 6-OHDA formation in the rat striatum. The present study provides novel information on L-DOPA-induced neurotoxicity and suggests the concomitant use of an antioxidant with L-DOPA in order to enhance the life span of L-DOPA therapy.

Aspirin curtails the acetaminophen-induced rise in brain norepinephrine levels.

We previously showed that acetaminophen administration to rats increases forebrain serotonin levels as a result of the inhibition of liver tryptophan-2,3-dioxygenase (TDO). In this study we determined whether aspirin alone and in combination with acetaminophen could further influence brain serotonin as well as norepinephrine levels and if so whether the status of the liver TDO activity would be altered. The results show that acetaminophen alone increases brain serotonin as well as norepinephrine levels with a concomitant inhibition of liver TDO activity. In contrast, aspirin did not alter the levels of these monoamines but increased serotonin turnover in the brain while acetaminophen decreased the turnover. When combined with acetaminophen, aspirin overrides the reduced serotonin turnover induced by acetaminophen. This report demonstrates the potential of these agents to alter neurotransmitter levels in the brain.