Melatonin Protects against Apoptosis-Inducing Factor (AIF)-Dependent Cell Death during Acetaminophen-Induced Acute Liver Failure

Liang, Ying-Li; Zhang, Zhihui; Liu, Xiaojing; Liu, Xiaoqian; Li, Tao; Zhang, Ye-Fa; Wang, Hua; Zhang, Cheng; Chen, Xi; D, Xu

doi:10.1371/journal.pone.0051911

Cited by 31 publications

(28 citation statements)

References 44 publications

(47 reference statements)

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“…In addition, we have also observed that treatment with melatonin or oestrogens was able to decrease mRNA expression of AIF. Our data were in agreement with previous reports in which melatonin was able to prevent the insult-related release of AIF from mitochondria (Liang et al 2012). Bethea et al (Bethea et al 2009) showed that AIF gene expression was significantly decreased by hormone therapy (E and E+P-treated animals) in laser-captured serotoninergic neurons.…”

Section: Discussionsupporting

confidence: 94%

Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats

Kireev

Vara

Viña

et al. 2014

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The aim of this study was to determine the outcomes of oestrogen and melatonin treatments following long-term ovarian hormone depletion on neuroinflammation and apoptotic processes in dentate gyrus of hippocampi. Forty-six female Wistar rats of 22 months of age were used. Twelve of them remained intact, and the other 34 were ovariectomized at 12 months of age. Ovariectomized animals were divided into three groups and treated for 10 weeks with oestrogens, melatonin or saline. All rats were killed by decapitation at 24 months of age, and dentate gyri were collected. A group of 2 month-old intact female rats was used as young control. The levels of pro-inflammatory cytokines and heat shock protein 70 (HSP 70) were analysed by ELISA. The expressions of TNFα, IL1β, GFAP, nNOS, iNOS, HO-1, NFκB, Bax, Bad, AIF, Bcl2 and SIRT1 genes were detected by real-time (RT)-PCR. Western blots were used to measure the protein expression of NFκB p65, NFκB p50/105, IκBα, IκBβ, p38 MAPK, MAP-2 and synapsin I. We have assessed the ability of 17β-oestradiol and melatonin administration to downregulate markers of neuroinflammation in the dentate gyrus of ovariectomized female rats. Results indicated that 17β-oestradiol and melatonin treatments were able to significantly decrease expression of pro-inflammatory cytokines, iNOS and HO-1 in the hippocampus when compared to non-treated animals. A similar age-and long-term ovarian hormone depletion-related increase in GFAP was also attenuated after both melatonin and oestradiol treatments. In a similar way to oestradiol, melatonin decreased the activation of p38 MAPK and NFκB pathways. The treatments enhanced the levels of synaptic molecules synapsin I and MAP-2 and have been shown to modulate the pro-antiapoptotic ratio favouring the second and to increase SIRT1 expression. These findings support the potential therapeutic role of melatonin and oestradiol as protective antiinflammatory agents for the central nervous system during menopause.

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Section: Discussionsupporting

confidence: 94%

Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats

Kireev

Vara

Viña

et al. 2014

AGE

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“…This metabolite is normally rendered harmless through its interaction with glutathione (GSH), an endogenous antioxidant (11,12) However, when this APAP metabolite is overproduced, GSH stores in the liver become depleted, the metabolite accumulates, and tissue injury occurs (13). As a result, APAP overdose stimulates the apoptotic and/or necrotic death signaling pathways in cellular models (14,15). Additionally, APAP overdose increases oxidative stress and reactive oxygen species (ROS) levels, decreases GSH levels, induces mitogen-activated protein kinase (MAPK) signaling pathways, and activates caspase cascades (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

2019

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Acetaminophen (APAP) is a widely used analgesic and antipyretic. It is safe at normal treatment doses; however, APAP overdose is a major cause of acute liver and kidney failure. A variety of methods to reduce the damage caused by APAP overdose have previously been evaluated. The protein-rich seaweed Pyropia yezoensis has antioxidant, antitumor and anti-inflammatory activities, and protects against cytotoxicity. However, little is known regarding the protective effects of P. yezoensis peptide against APAP-induced hepatotoxicity. The present study investigated the ability of P. yezoensis peptide (PYP1-4) to ameliorate the damage caused by APAP-induced hepatotoxicity using HepG2 as the model cell line in addition to the signaling pathways involved. Briefly, cell viability, nitric oxide, reactive oxygen species and apoptosis assays were performed in conjunction with western blot analysis and reverse transcription-quantitative PCR. First, the present study revealed the minimum toxic concentration of APAP (15 mM) and the resting concentration of PYP1-4 (0-500 ng/ml). Administration of PYP1-4 to APAP-induced cells decreased the nitric oxide and reactive oxygen species levels, and restored the levels of antioxidant-associated proteins (catalase, heme oxygenase 1, superoxide dismutase 2 and quinone oxidoreductase 1). PYP1-4 increased the translocation of nuclear factor, erythroid 2 like 2 to the nucleus and the activities of glycogen synthase kinase-3β, Akt and AMP-activated protein kinase. In addition, APAP induced apoptosis; however, PYP1-4 inhibited apoptosis by modulating the levels of pro-apoptotic markers (Bad), anti-apoptotic markers (Bcl-2 and BH3 interacting domain death agonist), caspases and poly (ADP-ribose) polymerase 1. Subsequently, the insulin-like growth factor 1 receptor signaling pathway was investigated to determine whether PYP1-4 treatment restored the levels of cell growth-associated factors during APAP-induced hepatotoxicity. PYP1-4 treatment impacted the levels of components of the insulin receptor substrate 1/PI3K/Akt and Ras/Raf/ERK signaling pathways, and promoted cell survival. Therefore, the P. yezoensis peptide PYP1-4 may be useful for preventing APAP-induced hepatotoxicity.

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“…All in all, it appears that the TRYCAT pathway is regulated in a complex manner by many different processes. It should also be borne in mind that the placenta is a significant source of melatonin for mother and foetus, which has antioxidant and antiinflammatory effects, as well as protecting mitochondria at the consequences of CYP2E1 induction (Liang et al 2012).…”

Section: Discussionmentioning

confidence: 99%

IgM-mediated autoimmune responses to oxidative specific epitopes, but not nitrosylated adducts, are significantly decreased in pregnancy: association with bacterial translocation, perinatal and lifetime major depression and the tryptophan catabolite (TRYCAT) pathway

et al. 2017

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Immunoglubulin (Ig)M responses directed to oxidative specific epitopes (OSEs) and nitric oxide (NO)-adducts are significantly associated with major depression and physio-somatic symptoms. End of term serum IgM responses to OSEs and NO-adducts were assayed in pregnant women with (n = 24) and without prenatal depression (n = 25) as well as in 24 non-pregnant women. Associations of IgM/IgA responses to Gram-negative gut commensal bacteria (leaky gut index) and IgA/IgM responses to tryptophan catabolites (TRYCATs) were analyzed. IgM responses to OSEs, but not NO-adducts, were significantly reduced at the end of term. There were no significant associations between IgM responses to OSEs and perinatal depression, whilst IgM responses to NO-adducts, especially NO-cysteinyl, were significantly associated with a lifetime major depression. IgM responses to OSEs and NO-cysteinyl were significantly associated with IgA/IgM responses to Gram-negative bacteria, especially Morganella morganii, Klebsiella pneumoniae and Citrobacter koseri. IgM responses to NO-adducts and OSEs, especially malondialdehyde and myristic acid, and C-reactive protein (CRP) were inversely associated with TRYCAT pathway activity, whilst a lifetime depression and Pseudomonas putida were positively associated. The attenuation of natural IgM-mediated responses to OSEs at the end of term may indicate lowered activity of this part of the compensatory (anti-)inflammatory reflex system and may be partly explained by lowered bacterial translocation. Increased IgM responses to NO-cysteinyl is a biomarker of lifetime depression and may be induced by bacterial translocation. Natural IgM-mediated autoimmune responses, increased nitrosylation and higher CRP levels may have negative regulatory effects on the TRYCAT pathway.

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Melatonin Protects against Apoptosis-Inducing Factor (AIF)-Dependent Cell Death during Acetaminophen-Induced Acute Liver Failure

Cited by 31 publications

References 44 publications

Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats

Melatonin and oestrogen treatments were able to improve neuroinflammation and apoptotic processes in dentate gyrus of old ovariectomized female rats

PYP1‑4 peptide from Pyropia yezoensis protects against acetaminophen‑induced hepatotoxicity in HepG2 cells

IgM-mediated autoimmune responses to oxidative specific epitopes, but not nitrosylated adducts, are significantly decreased in pregnancy: association with bacterial translocation, perinatal and lifetime major depression and the tryptophan catabolite (TRYCAT) pathway

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