Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR‐induced depletion, and protects against the formation of DNA damage (8‐hydroxy‐2'‐deoxyguanosine) in ex vivo human skin

Fischer, Tobias W.; Kleszczyński, Konrad; Hardkop, Lena H.; Kruse, Nathalie; Zillikens, Detlef

doi:10.1111/jpi.12018

Cited by 285 publications

(248 citation statements)

References 70 publications

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“…These findings suggest that the protective mechanism of melatonin against burn- induced liver injury could be closely associated with HO-1 overexpression and increased cellular antioxidant capacity. Our data are in accordance with data regarding the protective effect of melatonin on DNA damage related to the increased expression of antioxidant enzymes SOD, catalase and Gpx in ex vivo human skin (Fischer et al 2013).…”

Section: Discussionsupporting

confidence: 81%

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

Bekyarova¹,

Tzaneva²,

Hristova³

2015

Vet. Med. - Czech

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Melatonin exerts beneficial effects on early liver injury by modulating hepatic oxidative stress. In order to understand the protective effect of melatonin against burn-induced hepatic injury we investigated the expression of 4-hydroxynonenal (4-HNE), a main product of lipid peroxidation and mediator of oxidative injury, the inducible heme-oxygenase-1 (HO-1), an antioxidant enzyme, and the anti-oxidative stress regulator erythroid 2-related factor 2 (Nrf2) in a burn rat model. Expression and localisation of HO-1, 4-HNE and Nrf2 in liver were investigated using light immunochemistry. Thermal skin injury caused a significant elevation in hepatic 4-HNE and degenerative liver changes. Concurrently, there was increased expression of HO-1, a rate-limiting enzyme for haem degradation and an oxidative stress marker in sinusoidal endothelial cells (SECs) and hepatocytes without changes in Nrf2 expression in the liver. Melatonin (20 mg/kg b.w.) augmented the increase in HO-1 expression, upregulated Nrf2 expression and also led to decreased 4-HNE levels and reduced levels of histopathological changes in rat liver. In conclusion, our results suggest that melatonin ameliorates burn-induced liver injury through the inhibition of oxidative stress, upregulation of the antioxidant enzyme HO-1 and activation of the antioxidant Nrf2 pathway. Stimulation of cellular protective mechanisms by activating the antioxidant stress response through Nrf2 is a new mechanism for protection against liver damage in burns.

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Section: Discussionsupporting

confidence: 81%

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

Bekyarova¹,

Tzaneva²,

Hristova³

2015

Vet. Med. - Czech

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“…There is also evidence that melatonin protects skin from UV injury by enhancing the expression of SOD, catalase, and GPx (Fischer et al, 2013). Some experimental models of tissue damage demonstrate that melatonin acts protectively by reducing oxidative stress and lipid peroxidation (Pieri et al, 1995;Reiter et al, 1998).…”

Section: Antioxidative Effects Of Melatoninmentioning

confidence: 99%

Prooxidant effects of melatonin: a brief review

Munik¹,

Ekmekçioğlu²

2015

Turk J Biol

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IntroductionMelatonin, chemically N-acetyl-5-methoxytryptamine, was primarily isolated from bovine pineal glands and its structure was first identified in 1958 (Lerner et al., 1958). This indolamine was later discovered to be also present or synthesized in extrapineal tissues such as the retina, gastrointestinal tract, Harderian gland, testes, and lymphocytes (Reiter et al., 2013). Due to the fact that melatonin possesses hydrophilic and lipophilic characteristics, its lipophilic ability enables it to penetrate all biological membranes, including the blood-brain barrier (Reiter et al., 1997). Generally, melatonin derives from the essential amino acid tryptophan by a multistep enzymatic reaction chain, including tryptophan 5-hydroxylation, decarboxylation, N-acetylation, and O-methylation. Furthermore, melatonin can be synthesized via O-methylation of serotonin and subsequent N-acetylation of 5-methoxytryptamine, or by O-methylation of tryptophan, followed by decarboxylation and N-acetylation (Hardeland et al., 1993). From a functional perspective, melatonin is characterized as a hormone involved in the regulation of the circadian rhythm of several biological functions and it also plays an important role in immunoregulation, reproduction, sleep, and inflammatory responses (Hardeland and Fuhrberg, 1996;Reiter et al., 2000). MT 1 and MT 2 are two well-characterized G protein-coupled plasma membrane melatonin receptors, which are activated by melatonin and regulate multiple cellular and physiological functions, including neuronal activity, arterial vasoconstriction, cell proliferation, immune responses, reproduction, and metabolic functions (Stankov and Reiter, 1990;Dubocovich and Markowska, 2005;Ekmekçioğlu, 2006Ekmekçioğlu, , 2014. In addition, melatonin has high-affinity binding for nuclear receptors ROR/RZR, which operate as transcriptional activators, and it also interacts with other intracellular proteins, like quinone reductase-2 (or MT 3 ) and calmodulin (Reppert et al., 1994;Wiesenberg et al., 1998). For the regulation of gene expression, it has been proposed that ROR/RZR work in cooperation with the plasma membrane receptors MT 1 /MT 2 (Carrillo-Vico et al., 2005). Regarding the regulation of the cellular redox status, melatonin possibly interacts with quinone reductase, even though the detailed role of this interaction remains poorly understood .Melatonin and calmodulin possess low-affinity interaction, which may relate to their antioxidant actions, as well as other signaling processes (Luchetti et al., 2010). Various studies describe melatonin and its derivatives as broad-spectrum antioxidants, related to their ability to Abstract: Melatonin acts classically through the widely expressed G protein-coupled membrane receptors MT 1 and MT 2 , respectively. The functional role of the MT receptors is not fully clear with multiple effects, such as effects on the circadian, reproductive, immune, cardiovascular, and intestinal systems, being suggested. In addition to receptor-mediated effects, melatonin also acts ...

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“…Melatonin serves a significant role in a wide variety of biological processes, including sleep, immunomodulation, anti-inflammation and antioxidative stress (8)(9)(10)(11). In addition, melatonin is an anticancer hormone and a potential target for cancer treatments (12).…”

Section: Introductionmentioning

confidence: 99%

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

et al. 2017

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Abstract. Melatonin, which is synthesized by the pineal gland and released into the blood, exhibits antitumor properties. However, the mechanisms underlying these effects, particularly in stomach cancer, remain unknown. In the present study, the effect of melatonin on the nuclear factor (NF)-κB signaling pathway and the mitogen-activated protein kinase signaling pathway, involving p38 and c-Jun-N-terminal kinase (JNK), were investigated in SGC7901 gastric cancer cells. In addition, the effect of melatonin on the survival, migration and apoptosis of these cells was investigated in vitro in order to evaluate the use of melatonin for the treatment of gastric cancer. The results of the present study revealed that melatonin decreased the viability and migration of SGC7901 cells. Furthermore, melatonin induced apoptosis. Melatonin was identified to elevate the expression levels of phosphorylated (p)-p38 and p-JNK protein, and decrease the expression level of nucleic p-p65. These results suggest that the protein levels of p65, p38 and JNK are associated with the survival of SGC7901 cells following treatment with melatonin. The optimal concentration of melatonin was demonstrated to be 2 mM, which significantly induced apoptosis following a 24 h treatment period. These findings suggest that conflicting growth signals in cells may inhibit the efficacy of melatonin in the treatment of gastric cancer. Therefore, adjunct therapy would be required to improve the efficacy of melatonin in the treatment of cancer. IntroductionGastric carcinoma is one of the most common types of malignancy, worldwide (1). In Asia, patients tend to be diagnosed at an average age of 66.8 years, and exhibit poor rates of survival (1). Gastric cancer is a refractory cancer and the third-leading cause of cancer-associated mortality in China (2). Gastric adenocarcinoma is the predominant type of gastric cancer and has limited treatment options (3). The typical treatments for gastric cancer, surgery and chemotherapy, only partially improve the overall survival of patients with this disease (4,5). Therefore, more effective drugs or comprehensive therapies are required (6).Melatonin is an indole hormone secreted by the pineal gland and was first identified in 1958 (7). Melatonin serves a significant role in a wide variety of biological processes, including sleep, immunomodulation, anti-inflammation and antioxidative stress (8-11). In addition, melatonin is an anticancer hormone and a potential target for cancer treatments (12). Several studies have revealed that melatonin is useful for the prevention of cancer (13,14). The antitumor ability of melatonin may be mediated by numerous mechanisms, including the activation of antioxidative stress, inhibition of migration and induction of apoptosis (15)(16)(17). Melatonin has also been demonstrated to suppress the growth, migration and invasion of SGC7901 gastric cancer cells in vitro (18), and to exert an apoptotic effect in the hepatocellular carcinoma HepG2 cell line (19). Additionally, the use of melatonin h...

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Melatonin enhances antioxidative enzyme gene expression (CAT, GPx, SOD), prevents their UVR‐induced depletion, and protects against the formation of DNA damage (8‐hydroxy‐2'‐deoxyguanosine) in ex vivo human skin

Cited by 285 publications

References 70 publications

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

Melatonin protects against burn-induced hepatic oxidative injury by inducing HO-1 via the Nrf2 pathway

Prooxidant effects of melatonin: a brief review

Melatonin treatment induces apoptosis through regulating the nuclear factor-κB and mitogen-activated protein kinase signaling pathways in human gastric cancer SGC7901 cells

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