TCDD Decreases Rapidly and Persistently Serum Melatonin Concentration Without Morphologically Affecting the Pineal Gland in TCDD‐Resistant Han/Wistar Rats

Lindén, Jere; Pohjanvirta, Raimo; Rahko, Timo; Tuomisto, Jouko

doi:10.1111/j.1600-0773.1991.tb01325.x

Cited by 23 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[73] found that exposure of LE rats to an extremely toxic environmental contaminant, 2,3,7,8‐tetrachlorodibenzo‐ p ‐dioxin (TCDD), was accompanied by a rapid reduction in circulating melatonin levels both during day and at night. In the follow‐up study [74], they confirmed, in another rat strain (Han/Wister rats), that TCDD administration also resulted in a similar rapid but persistent reduction in circulating melatonin.…”

Section: Melatonin Biosynthesismentioning

confidence: 83%

One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species?

Tan

Manchester

Terrón

et al. 2006

Journal of Pineal Research

1,431

1,219

View full text Add to dashboard Cite

Melatonin is a highly conserved molecule. Its presence can be traced back to ancient photosynthetic prokaryotes. A primitive and primary function of melatonin is that it acts as a receptor-independent free radical scavenger and a broad-spectrum antioxidant. The receptor-dependent functions of melatonin were subsequently acquired during evolution. In the current review, we focus on melatonin metabolism which includes the synthetic rate-limiting enzymes, synthetic sites, potential regulatory mechanisms, bioavailability in humans, mechanisms of breakdown and functions of its metabolites. Recent evidence indicates that the original melatonin metabolite may be N 1 -acetyl-N 2 -formyl-5-methoxykynuramine (AFMK) rather than its commonly measured urinary excretory product 6-hydroxymelatonin sulfate. Numerous pathways for AFMK formation have been identified both in vitro and in vivo. These include enzymatic and pseudo-enzymatic pathways, interactions with reactive oxygen species (ROS)/reactive nitrogen species (RNS) and with ultraviolet irradiation. AFMK is present in mammals including humans, and is the only detectable melatonin metabolite in unicellular organisms and metazoans. 6-Hydroxymelatonin sulfate has not been observed in these low evolutionary-ranked organisms. This implies that AFMK evolved earlier in evolution than 6-hydroxymelatonin sulfate as a melatonin metabolite. Via the AFMK pathway, a single melatonin molecule is reported to scavenge up to 10 ROS/RNS. That the free radical scavenging capacity of melatonin extends to its secondary, tertiary and quaternary metabolites is now documented. It appears that melatonin's interaction with ROS/RNS is a prolonged process that involves many of its derivatives. The process by which melatonin and its metabolites successively scavenge ROS/RNS is referred as the free radical scavenging cascade. This cascade reaction is a novel property of melatonin and explains how it differs from other conventional antioxidants. This cascade reaction makes melatonin highly effective, even at low concentrations, in protecting organisms from oxidative stress. In accordance with its protective function, substantial amounts of melatonin are found in tissues and organs which are frequently exposed to the hostile environmental insults such as the gut and skin or organs which have high oxygen consumption such as the brain. In addition, melatonin production may be upregulated by low intensity stressors such as dietary restriction in rats and exercise in humans. Intensive oxidative stress results in a rapid drop of circulating melatonin levels. This melatonin decline is not related to its reduced synthesis but to its rapid consumption, i.e. circulating melatonin is rapidly metabolized by interaction with ROS/RNS induced by stress. Rapid melatonin consumption during elevated stress may serve as a protective mechanism of organisms in which melatonin is used as a first-line defensive molecule against oxidative damage. The oxidative status of organisms modifies melatonin metabolism. It h...

show abstract

Section: Melatonin Biosynthesismentioning

confidence: 83%

One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species?

Tan

Manchester

Terrón

et al. 2006

Journal of Pineal Research

1,431

1,219

View full text Add to dashboard Cite

show abstract

“…In other cases, a melatonin deficiency can be a result of external or environmental toxicity. Rats treated with a strong oxidant such as 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) also experience reduced melatonin levels [120,121,122]. Certainly, the dual sources of melatonin in organisms make it much more reliable as an antioxidant than others when it is needed.…”

Section: Melatonin An Inducible Antioxidantmentioning

confidence: 99%

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

et al. 2015

View full text Add to dashboard Cite

Abstract:Melatonin is a tryptophan-derived molecule with pleiotropic activities. It is present in almost all or all organisms. Its synthetic pathway depends on the species in which it is measured. For example, the tryptophan to melatonin pathway differs in plants and animals. It is speculated that the melatonin synthetic machinery in eukaryotes was inherited from bacteria as a result of endosymbiosis. However, melatonin's synthetic mechanisms in microorganisms are currently unknown. Melatonin metabolism is highly complex with these enzymatic processes having evolved from cytochrome C. In addition to its enzymatic degradation, melatonin is metabolized via pseudoenzymatic and free radical interactive processes. The metabolic products of these processes overlap and it is often difficult to determine which process is dominant. However, under oxidative stress, the free radical interactive pathway may be featured over the others. Because of the complexity of the melatonin degradative processes, it is expected that additional novel melatonin metabolites will be identified in future investigations. The original and primary function of melatonin in early life forms such as in unicellular organisms was as a free radical scavenger and antioxidant. During evolution, melatonin was selected as a signaling molecule to transduce the environmental photoperiodic information into an endocrine message in multicellular organisms and for other purposes as well. As an antioxidant, melatonin exhibits several unique features which differ from the classic antioxidants. These include its cascade reaction with free radicals and its capacity to be induced under moderate oxidative stress. These OPEN ACCESSMolecules 2015, 20 18887 features make melatonin a potent endogenously-occurring antioxidant that protects organisms from catastrophic oxidative stress.

show abstract

“…Moreover, in the rat GnV-3 hypothalamic cell line, TCDD (10 nM, 6 h) increased mRNA expression of NPY [ 49 ]. While increased expression of NPY or MCH (orexigenic factors) might be a paradox regarding the loss of appetite described following TCDD exposure, the regulation of those factors might be a little more complex in time; indeed, a biphasic effect of TCDD on orexigenic factors (an initial suppression followed by an increase in expression) has also been described [ 50 ]. More recently, a study of the effect of TCDD (1 µg/kg at GD15) on the fetal rat hypothalamus metabolome (at GD20) showed significant decreases of several amino acids (alanine, aspartate, glutamine, isoleucine, phenylalanine, and threonine) which could impact the levels of some neurotransmitters [ 51 ].…”

Section: Disruption Of Neuroendocrine Functions By Ahr Ligandsmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor and the Nervous System

Juricek

Coumoul

2018

IJMS

111

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (or AhR) is a cytoplasmic receptor of pollutants. It translocates into the nucleus upon binding to its ligands, and forms a heterodimer with ARNT (AhR nuclear translocator). The heterodimer is a transcription factor, which regulates the transcription of xenobiotic metabolizing enzymes. Expressed in many cells in vertebrates, it is mostly present in neuronal cell types in invertebrates, where it regulates dendritic morphology or feeding behavior. Surprisingly, few investigations have been conducted to unravel the function of the AhR in the central or peripheral nervous systems of vertebrates. In this review, we will present how the AhR regulates neural functions in both invertebrates and vertebrates as deduced mainly from the effects of xenobiotics. We will introduce some of the molecular mechanisms triggered by the well-known AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which impact on neuronal proliferation, differentiation, and survival. Finally, we will point out the common features found in mice that are exposed to pollutants, and in AhR knockout mice.

show abstract

TCDD Decreases Rapidly and Persistently Serum Melatonin Concentration Without Morphologically Affecting the Pineal Gland in TCDD‐Resistant Han/Wistar Rats

Cited by 23 publications

References 32 publications

One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species?

One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species?

Melatonin as a Potent and Inducible Endogenous Antioxidant: Synthesis and Metabolism

The Aryl Hydrocarbon Receptor and the Nervous System

Contact Info

Product

Resources

About