Hydroquinone exposure worsens the symptomatology of rheumatoid arthritis

Heluany, Cíntia Scucuglia; Kupa, Léonard de Vinci Kanda; Viana, Mariana Nascimento; Fernandes, C.M.; Farsky, Sandra Helena Poliselli

doi:10.1016/j.cbi.2018.06.016

Cited by 10 publications

(9 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, the expression of Casp1 and IL1β show significant difference between two groups and markedly upregulated in low dose benzene-exposed workers accompanied with serum IL1β release increased which confirmed the occurrence of pyroptosis. Others living animal experiment showed benzene metabolic exposure induced rats secreted higher levels of proinflammatory cytokines IL1β which support us results [10]. Furthermore, inflammation factors included in this study showed that IL8 was significantly higher while IL-10 show significantly lower levels in low dose benzene-exposed workers than controls.…”

Section: Discussionsupporting

confidence: 89%

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

et al. 2019

View full text Add to dashboard Cite

BackgroundLong term low-dose benzene exposure leads to the inhibition of haematopoiesis. However, the underlying mechanisms remained poorly defined, especially mediated by early effector molecules.MethodsHere, we first found in mRNA microarray that pyroptotic classic genes (Casp1, 4, 5, and IL1β) were up-regulated and represented dose-dependent differential expression in controls, low-dose benzene-exposed and chronic benzene-poisoned workers, and the expression of Casp1 and IL1β were confirmed in low-dose benzene-exposed workers and was accompanied with elevated potent proinflammatory IL1β. In vitro studies showed that benzene metabolites induced AHH-1 cell pyroptosis through activating Aim2/Casp1 pathway with the increased expression of GSDMD. Meanwhile, TET2 overexpression was elevated in vivo and in vitro and it was positively correlated with IL1β. Further, we verified that pyroptosis caused by 1,4-BQ could be ameliorated in vitro by RNAi or pretreatment with Dimethyloxalylglycine (DMOG), the inhibitor of TET2.FindingsExposure to benzene can trigger pyroptosis via TET2 directly regulating the Aim2/Casp1 signaling pathway to cause haematotoxicity.InterpretationBenzene metabolites induced pyroptotic cell death through activation of the Aim2/Casp1 pathway which can be regulated by Tet2 overexpression. Tet2 may be a potential risk factor and is implicated in the development of benzene-related diseases.FundNational Natural Science Foundation of China; the Support Project of High–level Teachers in Beijing Municipal Universities in the Period of 13th Five–year Plan; Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education.

show abstract

Section: Discussionsupporting

confidence: 89%

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The modulation of the cytosolic transcription factor aryl hydrocarbon receptor (AhR) linked to BZ toxicity on BM and blood cells has recently been investigated. AhR is a ligand-activated transcription factor expressed in hematopoietic progenitor cells, lymphocytes, neutrophils, and splenocytes [ 132 , 133 , 134 ]. The connection between BZ exposure and AhR was first demonstrated by studies that provided evidence that hematopoietic toxicity induced by BZ was not observed in AhR knockout mice, but that toxicity would take place when the BM of animals was repopulated with cells from wild-type mice.…”

Section: Cellular and Molecular Mechanisms Of Toxicity On Hematopomentioning

confidence: 99%

“…Although HQ-exposed animals had no alterations in BM or blood cell numbers, disease symptoms worsened, with a high frequency of AhR + neutrophils and Th17 lymphocytes in the inflamed synovia. Accordingly, rheumatoid arthritis symptoms were not observed in AhR knockout mice exposed to HQ [ 133 , 134 ] (Heluany et al, under review). These data evidence that exposure to BZ metabolites worsens rheumatoid arthritis involving HQ actions through AhR on blood cells, and that both BZ and HQ are cigarette compounds involved with the harmful effects on the evolution of the disease as a result of cigarette smoking.…”

Section: Cellular and Molecular Mechanisms Of Toxicity On Hematopomentioning

confidence: 99%

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis

Scharf

Broering

Rocha

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Hematopoiesis is a complex and intricate process that aims to replenish blood components in a constant fashion. It is orchestrated mostly by hematopoietic progenitor cells (hematopoietic stem cells (HSCs)) that are capable of self-renewal and differentiation. These cells can originate other cell subtypes that are responsible for maintaining vital functions, mediate innate and adaptive immune responses, provide tissues with oxygen, and control coagulation. Hematopoiesis in adults takes place in the bone marrow, which is endowed with an extensive vasculature conferring an intense flow of cells. A myriad of cell subtypes can be found in the bone marrow at different levels of activation, being also under constant action of an extensive amount of diverse chemical mediators and enzymatic systems. Bone marrow platelets, mature erythrocytes and leukocytes are delivered into the bloodstream readily available to meet body demands. Leukocytes circulate and reach different tissues, returning or not returning to the bloodstream. Senescent leukocytes, specially granulocytes, return to the bone marrow to be phagocytized by macrophages, restarting granulopoiesis. The constant high production and delivery of cells into the bloodstream, alongside the fact that blood cells can also circulate between tissues, makes the hematopoietic system a prime target for toxic agents to act upon, making the understanding of the bone marrow microenvironment vital for both toxicological sciences and risk assessment. Environmental and occupational pollutants, therapeutic molecules, drugs of abuse, and even nutritional status can directly affect progenitor cells at their differentiation and maturation stages, altering behavior and function of blood compounds and resulting in impaired immune responses, anemias, leukemias, and blood coagulation disturbances. This review aims to describe the most recently investigated molecular and cellular toxicity mechanisms of current major environmental pollutants on hematopoiesis in the bone marrow.

show abstract

“…Hydroquinone has aggravated systemic and local ra symptoms in in vivo rodent models, due to the migration of aryl hydrocarbon receptors into synovia, higher serum levels of anti -citrullinated peptides and of proinflammatory cytokines. The large number of neutrophils in the synovial fluid activate aryl hydrocarbon receptors and the interleukin 17 pathway, which are involved in immune-mediated diseases (21,22).…”

Section: Quinonesmentioning

confidence: 99%

Etiopathogenic mechanisms of tobacco constituents in rheumatoid arthritis

Macovei¹,

Cardoneanu²,

Burlui³

et al. 2019

Ro J Rheumatol.

View full text Add to dashboard Cite

Active smoking is considered a risk factor for rheumatoid arthritis. Smokers show respiratory extra-articular manifestations and complications, such as interstitial lung disease and chronic obstructive pulmonary disease. Smokers may receive a more intensive drug therapy than non-smokers, but they have a poor prognosis. Smoker's resistance to therapy may be caused by the pharmacokinetic interactions between drugs and tobacco constituents. The present account of some of those thousands of components of the gas and tar phase of cigarette smoke (polynuclear aromatic hydrocarbons, quinones, cyanide, heavy metals, bacterial endotoxins, nicotine and carbon monoxide) may help explain the inconclusive incrimination of tobacco use in the development of rheumatoid arthritis and convince more clinicians to recommend smoking cessation.

show abstract

Hydroquinone exposure worsens the symptomatology of rheumatoid arthritis

Cited by 10 publications

References 60 publications

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

Benzene metabolites trigger pyroptosis and contribute to haematotoxicity via TET2 directly regulating the Aim2/Casp1 pathway

Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis

Etiopathogenic mechanisms of tobacco constituents in rheumatoid arthritis

Contact Info

Product

Resources

About