Melatonin and vitamin E alleviate homocysteine‐induced oxidative injury and apoptosis in endothelial cells

Aykutoğlu, Gürkan; Tartik, Musa; Darendelioğlu, Ekrem; Ayna, Adnan; Baydaş, Gıyasettin

doi:10.1007/s11033-020-05607-z

Cited by 26 publications

(22 citation statements)

References 40 publications

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“…In line with our findings, the involvement of HCY in the induction of mitochondrial dysfunction in rat ischemic brain [31] and reproduction disorders including reduced fertility, suppressed fertilization, and the developmental competence of oocytes and embryos, increased risk of recurrent miscarriage, placental infarction, and congenital defects was reported [27,29,30]. In addition, the protective role of melatonin against HCY-induced oxidative injury, through decreasing the levels of Caspase-3 and BAX and increasing BCL2, has been observed in human umbilical vein endothelial cells (HUVECs) and hippocampus of rats [51,52]. Moreover, the high HCY levels observed in pinealectomized mouse highlights a potential linkage between the pineal hormone melatonin and the maintenance of the HCY levels [53].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Melatonin Alleviates the Toxicity of High Nicotinamide Concentrations in Oocytes: Potential Interaction with Nicotinamide Methylation Signaling

Sheikh

Mesalam

Song

et al. 2021

Oxidative Medicine and Cellular Longevity

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Despite the numerous studies on melatonin and nicotinamide (NAM, the active form of vitamin B3), the linkage between these two biomolecules in the context of signaling pathways regulating preimplantation embryo development has not yet been investigated. In this study, we used bovine oocyte model to elucidate the effect of melatonin on the developmental competence of oocytes under the stress of high NAM concentrations. Results showed that NAM (20 mM) administration during in vitro maturation (IVM) significantly reduced oocyte maturation and actin distribution, while induced reactive oxygen species (ROS) accumulation and mitochondrial dysfunction, the multiple deleterious effects that were alleviated by melatonin (10−7 M). The RT-qPCR and/or immunofluorescence showed upregulation of the apoptosis (Caspase-3, Caspase-9, and BAX), autophagy (Beclin-1, LC3A, LC3B, ATG7, LAMP1, and LAMP2), cell cycle (P21, P27, and P53), and DNA damage (COX2 and 8-OxoG) specific markers in oocytes matured under NAM treatment, compared to NAM-melatonin dual-treated and the untreated ones. In addition, the total cleavage and blastocyst development rate, as well as the total number of cells and the inner cell mass (ICM) per blastocyst, were reduced, while DNA fragmentation was induced, in the group of NAM sole treatment than NAM-melatonin cotreatment and control. Inspecting the underlying mechanisms behind NAM-associated toxicity revealed an increase in transcription pattern of NAM methylation (NNMT and AHCY) genes in NAM-treated oocytes while the opposite profile was observed upon melatonin supplementation. In conclusion, to our knowledge, this is the first study reporting that melatonin can protect oocytes and embryos from NAM-induced injury through its ROS-scavenging activity together with potential interaction with NAM methylation signaling.

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Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Melatonin Alleviates the Toxicity of High Nicotinamide Concentrations in Oocytes: Potential Interaction with Nicotinamide Methylation Signaling

Sheikh

Mesalam

Song

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…To avoid melatonin degradation, as well as improve the antioxidant activity of melatonin, other antioxidant agents such as vitamin E can be incorporated into the formulations [ 103 ]. In this regard, the oxidation of melatonin has been previously described by Reiter et al [ 104 ].…”

Section: New Melatonin Galenic Developments Addressed To Reduce the Toxicity Of Blister Agentsmentioning

confidence: 99%

Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?

et al. 2021

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Blister or vesicant chemical warfare agents (CWAs) have been widely used in different military conflicts, including World War I and the Iran-Iraq War. However, their mechanism of action is not fully understood. Sulfur and nitrogen mustard exert toxic effects not only through the alkylation of thiol-bearing macromolecules, such as DNA and proteins, but also produce free radicals that can develop direct toxic effects in target organs such as the eyes, skin, and respiratory system. The lack of effective treatments against vesicant CWAs-induced injury makes us consider, in this complex scenario, the use and development of melatonin-based therapeutic strategies. This multifunctional indoleamine could facilitate neutralization of the oxidative stress, modulate the inflammatory response, and prevent the DNA damage, as well as the long-term health consequences mediated by vesicant CWAs-induced epigenetic mechanisms. In this context, it would be essential to develop new galenic formulations for the use of orally and/or topically applied melatonin for the prophylaxis against vesicant CWAs, as well as the development of post-exposure treatments in the near future.

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“…Different in vivo reports recognized that the Th1-activity induced the Hcy inflammation response [298], and it appears that HHcy can be detected in chronic inflammatory conditions, even if vitamin B12 and folate are in range. A recent study promoted oxidative injury and apoptotic cell death in human umbilical vein endothelial cells by Hcy [299]. High level of Hcy promotes ROS accumulation in human umbilical vein endothelial cells through Hcy auto-oxidation that causes oxidative stress [286].…”

Section: Homocysteine and Oxidative Stressmentioning

confidence: 99%

Homocysteine in Neurology: A Risk Factor or Something Different in Small Vessel Disease

Moretti¹,

Caruso²,

Gazzin³

et al. 2020

Preprint

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Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Hyperhomocysteinemia (HHcy) is typically defined as levels >15 micro mols/L. Elevated plasma levels of Hcy can be caused by the deficiency of either vitamin B12 or folate. The active role of homocysteine is quite ambivalent: many studies detected its potential impact on neurological events; others try to identify it as one of the possible risk factors of cardiovascular events, but with a complementary and secondary role. HHcy has been reported in many neurologic disorders, including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. Nowadays, homocysteine could be considered as a possible link between a common vascular risk factor and potential alterations in degenerative neuronal disorders. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum stress; all these aspects have been considered to play an essential role in the pathogenesis of several diseases, including atherosclerosis, major stroke, and vascular dementia. Specific models of astrocytes impairment in HHcy-mice, which mimic small vessel disease, have been developed with a three-step investigation (at 6, 10, 14 weeks of B6, B9, and B12 detrimental diet in wild type HHcy mouse). These studies found out that after ten weeks on a diet (at the most after 14 weeks), end-feet disruption occurs. This phenomenon is concomitant to reduced vascular labeling for aquaporin -4-water channels, lower protein/mRNA levels for Kir4.1, and BK potassium channels, associated with a higher expression of MMP-9. The most exciting finding is that microglial activation in this mice model was evident since the precocious time of observation (6-week time) and precedes astrocytic changes. Our research aims to review the possible role of HHcy in neurodegenerative disease and small-vessel disease and to understand its pathogenic impact.

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Melatonin and vitamin E alleviate homocysteine‐induced oxidative injury and apoptosis in endothelial cells

Cited by 26 publications

References 40 publications

Melatonin Alleviates the Toxicity of High Nicotinamide Concentrations in Oocytes: Potential Interaction with Nicotinamide Methylation Signaling

Melatonin Alleviates the Toxicity of High Nicotinamide Concentrations in Oocytes: Potential Interaction with Nicotinamide Methylation Signaling

Toxicology of Blister Agents: Is Melatonin a Potential Therapeutic Option?

Homocysteine in Neurology: A Risk Factor or Something Different in Small Vessel Disease

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