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

Bekyarova, Ganka; Tzaneva, Maria; Hristova, Mariyana G.

doi:10.17221/8530-vetmed

Cited by 12 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One of the genes regulated through Nrf2 is heme oxygenase-1 ( HO-1 ). HO-1/Nrf2 have been shown to be involved in the protection of burn-induced hepatic oxidative injury, carbon tetrachloride-induced liver injury, nickel-induced DNA methylation, and inflammation ( 19 , 20 ). Nrf2 also plays a critical role in the mechanism of hepatic IR injury and is considered a potential therapeutic target for preventing hepatic IR injury during liver surgery ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Zhang

Yuan

Huang

et al. 2018

Braz J Med Biol Res

View full text Add to dashboard Cite

Nuclear factor erythroid-related factor 2 (Nrf2) has been implicated in several detoxifying and antioxidant defense processes. Nrf2-mediated heme oxygenase-1 (HO-1) expression was demonstrated to play a key role against oxidative stress. Gastrodin (GSTD) is a well-known active compound isolated from the roots of Rhizoma gastrodiae, a plant used in ancient Chinese traditional medicine. The aim of this work was to investigate whether GSTD could alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells (LSECs). In LSECs exposed to 1 mM H2O2, treatment with GSTD (1, 10, or 50 µM) resulted in higher cell viability than the untreated control. Treated cells maintained a higher Bcl2/Bax ratio and suppressed caspase-9 expression compared with untreated cells, reducing cell apoptosis. GSTD was protective for H2O2-induced oxidative injury by reducing the generation of intracellular reactive oxygen species and malondialdehyde. HO-1 and Nrf2 expressions were synergistically upregulated by GSTD. Inhibition of HO-1 by 10 µM zinc protoporphyrin resulted in less protective effects on cell viability and malondialdehyde reduction by GSTD treatment in H2O2-exposed LSECs. Additionally, phosphorylated p38 in LSECs exposed to H2O2 was elevated by GSTD. Inhibition of p38 phosphorylation by SB203580 did not induce Nrf2 and HO-1 expression after 1 or 10 µM GSTD treatment and the protective effect on cell viability and malondialdehyde reduction in H2O2-exposed LSECs was reduced. The data conclusively demonstrated that GSTD-induced HO-1 and Nrf2 expression is involved in protection of LSECs from H2O2-induced oxidative injury, which may be regulated by p38 phosphorylation.

show abstract

Section: Introductionmentioning

confidence: 99%

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Zhang

Yuan

Huang

et al. 2018

Braz J Med Biol Res

View full text Add to dashboard Cite

show abstract

“…In addition, we have previously demonstrated that GHP protected cellular damage by up-regulating the activities of SOD, CAT and GSH-Px in H 2 O 2 -stressed RAW 264.7 macrophages. Among the various cytoprotective enzymes, HO-1 can confer cytoprotection on a wide variety of cells against oxidative damage [ 35 ]. Moreover, HO-1 induction has been considered as a crucial beneficial mechanism to maintain homeostasis for the liver injury [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

Chen

et al. 2017

Nutrients

View full text Add to dashboard Cite

Oxidative stress is considered as an important mediator in the progression of metabolic disorders. The objective of this study was to investigate the potential hepatoprotective effects and mechanisms of bovine casein glycomacropeptide hydrolysates (GHP) on hydrogen peroxide (H2O2)-induced oxidative damage in HepG2 cells. Results showed that GHP significantly blocked H2O2-induced intracellular reactive oxygen species (ROS) generation and cell viability reduction in a dose-dependent manner. Further, GHP concentration-dependently induced heme oxygenase-1 (HO-1) expression and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) nuclear translocation. Moreover, pretreatment of GHP increased the activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated protein kinase 1/2 (ERK1/2), which were shown to contribute to Nrf2-mediated HO-1 expression. Taken together, GHP protected HepG2 cells from oxidative stress by activation of Nrf2 and HO-1 via p38 MAPK and ERK1/2 signaling pathways. Our findings indicate that bovine casein glycomacropeptide hydrolysates might be a potential ingredient in the treatment of oxidative stress-related disorders and further studies are needed to investigate the protective effects in vivo.

show abstract

“…Induction of Nrf2 has also been associated with the effects of melatonin in reducing oxidative and nitrosative DNA damage [ 312 ]. In fact, numerous investigations have shown that melatonin activates phase-2 antioxidative enzymes, via the Nrf2 pathway, including heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GSC), nicotinamide adenine dinucleotide phosphate (NADPH): quinone dehydrogenase-1 (NQO1) and SOD [ 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 , 328 , 329 , 330 , 331 , 332 , 333 ].…”

Section: Antioxidant Protectionmentioning

confidence: 99%

Melatonin: A Versatile Protector against Oxidative DNA Damage

2018

View full text Add to dashboard Cite

Oxidative damage to DNA has important implications for human health and has been identified as a key factor in the onset and development of numerous diseases. Thus, it is evident that preventing DNA from oxidative damage is crucial for humans and for any living organism. Melatonin is an astonishingly versatile molecule in this context. It can offer both direct and indirect protection against a wide variety of damaging agents and through multiple pathways, which may (or may not) take place simultaneously. They include direct antioxidative protection, which is mediated by melatonin’s free radical scavenging activity, and also indirect ways of action. The latter include, at least: (i) inhibition of metal-induced DNA damage; (ii) protection against non-radical triggers of oxidative DNA damage; (iii) continuous protection after being metabolized; (iv) activation of antioxidative enzymes; (v) inhibition of pro-oxidative enzymes; and (vi) boosting of the DNA repair machinery. The rather unique capability of melatonin to exhibit multiple neutralizing actions against diverse threatening factors, together with its low toxicity and its ability to cross biological barriers, are all significant to its efficiency for preventing oxidative damage to DNA.

show abstract

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

Cited by 12 publications

References 38 publications

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Gastrodin induced HO-1 and Nrf2 up-regulation to alleviate H2O2-induced oxidative stress in mouse liver sinusoidal endothelial cells through p38 MAPK phosphorylation

Casein Glycomacropeptide Hydrolysates Exert Cytoprotective Effect against Cellular Oxidative Stress by Up-Regulating HO-1 Expression in HepG2 Cells

Melatonin: A Versatile Protector against Oxidative DNA Damage

Contact Info

Product

Resources

About