Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases

Giménez, Virna Margarita Martín; Heras, Natalia de las; Ferder, León; Lahera, Vicente; Reíter, Russel J.; Manucha, Walter

doi:10.3390/diseases9020030

Cited by 21 publications

(19 citation statements)

References 206 publications

(209 reference statements)

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“…Anti-inflammatory actions of melatonin have become more and more apparent during the last years, although earlier assumptions had focused on the proinflammatory potential of this agent. This shall not be discussed here in all details, because this topic was addressed in several recent reviews [ 22 , 23 , 225 , 226 , 227 , 228 , 229 , 230 , 231 , 232 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 ]. Instead, a few decisive findings shall be highlighted.…”

Section: Consequences To Inflammation and Mitochondrial Integritymentioning

confidence: 99%

Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds

Hardeland

2021

Molecules

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Melatonin and several of its metabolites are interfering with reactive nitrogen. With the notion of prevailing melatonin formation in tissues that exceeds by far the quantities in blood, metabolites come into focus that are poorly found in the circulation. Apart from their antioxidant actions, both melatonin and N1-acetyl-5-methoxykynuramine (AMK) downregulate inducible and inhibit neuronal NO synthases, and additionally scavenge NO. However, the NO adduct of melatonin redonates NO, whereas AMK forms with NO a stable product. Many other melatonin metabolites formed in oxidative processes also contain nitrosylatable sites. Moreover, AMK readily scavenges products of the CO2-adduct of peroxynitrite such as carbonate radicals and NO2. Protein AMKylation seems to be involved in protective actions.

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Section: Consequences To Inflammation and Mitochondrial Integritymentioning

confidence: 99%

Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds

Hardeland

2021

Molecules

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“…Aging and age-related diseases also correlate with increasing mtDNA damage [6]. What is even more interesting, the overall condition of mitochondria may indicate the active SARS-CoV-2 infection [7]. The recent review stated that aging-like degradation and loss of mitochondrial function have been observed in COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

“…The recent review stated that aging-like degradation and loss of mitochondrial function have been observed in COVID-19 patients. Furthermore, during COVID-19 infection increased number of damaged mitochondria accumulated in the cell and led to a higher inflammation rate [7]. Approximately 30% of mitochondrial proteins are present in both, mitochondria, and cytoplasm, and/or nucleus.…”

Section: Introductionmentioning

confidence: 99%

The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

2021

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The 5′,8-cyclo-2′-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered—the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5′-end side of cdPu than on its 3′-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded.

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“…Surprisingly, mitochondrial MT constitutes more than 95% of total MT production [ 60 ]. On the other hand, MT plays a pivotal role in the regulation of mitochondrial biogenesis and in maintaining their homeostasis (referred to as mitoprotection), which involves, for example, reduced cytochrome c release and lowered Ca 2+ overload [ 62 , 63 ].…”

Section: Introductionmentioning

confidence: 99%

Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis—A New Look on an Old Story: A Review

et al. 2021

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Atopic dermatitis (AD) is common inflammatory dermatosis, typically with chronic and recurrent course, which significantly reduces the quality of life. Sleep disturbances are considered to be remarkably burdensome ailments in patients with AD, and are routinely included during assessment of disease severity. Therefore, endogenous substances engaged in the control of circadian rhythms might be important in pathogenesis of AD and, possibly, be used as biomarkers of disease severity or even in development of novel therapies. Melatonin (MT), the indoleamine produced by pineal gland (but also by multiple other tissues, including skin), plays a pivotal role in maintaining the sleep/wake homeostasis. Additionally, it possesses strong antioxidant and anti-inflammatory properties, which might directly link chronic skin inflammation and sleep abnormalities characteristic of AD. The objective of this work is to systematically present and summarize the results of studies (both experimental and clinical) that investigated the role of MT in the AD, with a focus on the antioxidant and immunomodulatory effects of MT.

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Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases

Cited by 21 publications

References 206 publications

Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds

Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds

The Influence of 5′,8-Cyclo-2′-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study

Melatonin as an Antioxidant and Immunomodulator in Atopic Dermatitis—A New Look on an Old Story: A Review

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