Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats

Zhao, Zongbiao; Ji, Ke; Shen, Xin-yue; Zhang, Wenwen; Wang, Rui; Xu, Weiping; Wei, Wei

doi:10.1016/j.etap.2019.03.008

Cited by 58 publications

(17 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although epidemiological studies have suggested that TBPH exposure is associated with several potential health risks (Liu et al, 2016), limited studies have focused on the hepatotoxicity of TBPH, and in particular, the possible mechanism has not been clearly elucidated. Zhao et al found that like DEHP, TBPH exposure induces oxidative stress and markedly promoted liver necrosis and fibrosis, and the increased expression of the proteins associated with liver inflammation, including P-Smad2, P-Smad3, and NF-κB (P65) (Zhao et al, 2019). This increasing trend in oxidative stress caused by TBPH exposure is consistent with the results of our study.…”

Section: Discussionsupporting

confidence: 92%

“…The similar structure and metabolic pathway of TBPH to DEHP suggest that TBPH may have similar biological toxic effects as DEHP (Roberts et al, 2012). Increasing toxicological evidence has documented that exposure to DEHP at certain levels has hepatorenal toxicity, and that oxidative stress is thought to be one of the possible mechanisms (Praveena et al, 2018;Zhao et al, 2019). However, any link between TBPH exposure and liver injury remains unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate on liver injury in Balb/c mice

Yin

Bao

2021

Toxicol Ind Health

View full text Add to dashboard Cite

Bis(2-ethylhexyl) 2,3,4,5-tetrabromophthalate (TBPH) has been used as a replacement in some commercial flame-retardant mixtures. It is widely used in industrial products, so the probability of human exposure to TBPH is high. Yet, little is known about how it is metabolized or its toxicity. To this end, we investigated what effect oral exposure of Balb/c mice to TBPH at concentrations of 200 mg kg−1 had on hepatic damage. Staining results showed liver injury in the mice exposed to TBPH. Oxidative stress markers and endoplasmic reticulum stress associated proteins were altered in the TBPH exposed mice, and these changes could be attenuated by administration of curcumin at 25 mg kg−1. Overall, TBPH induces hepatic damage via increasing oxidative stress, and curcumin plays a protective role in alleviating the TBPH-mediated histopathological alterations in the liver.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Effects of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate on liver injury in Balb/c mice

Yin

Bao

2021

Toxicol Ind Health

View full text Add to dashboard Cite

show abstract

“…As an environmental endocrine disruptor, DEHP has toxic effects in vertebrates. Increasing evidence manifested that DEHP can cause oxidative stress, inflammation and dysfunction in different glands (Zhao et al, 2019;Bahrami et al, 2018). Inhibition of oxidative stress and inflammation by regulating their corresponding signaling pathways would be an effective therapeutic treatment assuaging DEHP-induced thyrotoxicity in inflammasomes activation.…”

Section: Discussionmentioning

confidence: 99%

Rosmarinic acid alleviates di-2-ethylhexyl phthalate (DEHP) -induced thyroid dysfunction via multiple inflammasomes activation

Xiaolin

2020

J. Toxicol. Sci.

View full text Add to dashboard Cite

DEHP (di-2-ethylhexyl phthalate), an environmental endocrine disruptor, is widely used in industrial products, particularly as plasticizers and softeners which could disrupt the function of the hypothalamic-pituitary-thyroid (HPT) axis. Rosmarinic acid (RA) possesses potential antioxidant and anti-inflammatory capacities in disease models. Nevertheless, evidence on the association between DEHP-induced thyroid dysfunction and inflammation, as well as the molecular mechanism underlying the protective effects of RA-mitigated DEHP-induced thyroid injury remains inconclusive. Male Sprague Dawley (SD) rats were intragastrically administered DEHP (150 mg/kg, 300 mg/kg, 600 mg/kg) once a day for 90 consecutive days. Also, FRTL-5 cells were treated with a wide range of DEHP concentrations (10 -8 , 10 -7 , 10 -6 , 10 -5 , 10 -4 , 10 -3 , 10 -2 M) for 24 hr. Subsequently, RA (50 μM) was administered for 24 hr before 10 -4 M DEHP challenge. We found that DEHP induced thyroid damage and inflammatory infiltration in vivo. In addition, we showed that DEHP triggered inflammatory cell death, which is mediated by multiple inflammasomes. Moreover, RA, pyroptosis inhibitor (Ac-YVAD-cmk) and antioxidant inhibitor (NAC) treatment significantly alleviated DEHP-induced thyrocyte death, suppressing pro-inflammatory cytokine production, inhibiting multiple inflammasomes activation and attenuating thyrocyte death, respectively. Collectively, our results reveal that a critical role of inflammasomes activation in DEHP-induced thyroid injury, and suggest that RA confers protection against DEHP-induced thyroid inflammation, and facilitating control of the effects of DEHP after given pyroptosis inhibitor or antioxidant inhibitor. These results indicate that it should be possible to provide novel insights into toxicologically and pharmacologically targeting this molecule to DEHP-induced inflammation.

show abstract

“…On the other hand, DEPH has been associated with hepatic fibrosis and pro-inflammatory phenomena as a result of observable increments in steatosis, hepatocyte necrosis, and immune infiltration after TNF-α and IL-6 increments following different doses of DEPH in addition to increased levels of profibrogenic factors such as α-SMA, COL-I, COL-III, and TGF-β1 in LX-2 cells [ 136 ]. In this regard, TGF-β1 turns HSCs into a DEPH-susceptible population [ 137 ].…”

Section: Mechanisms Of Action Of Endocrine-disrupting Chemicals In Nafldmentioning

confidence: 99%

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Cano

Pérez

Angarita

et al. 2021

IJMS

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder, affecting around 25% of the population worldwide. It is a complex disease spectrum, closely linked with other conditions such as obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome, which may increase liver-related mortality. In light of this, numerous efforts have been carried out in recent years in order to clarify its pathogenesis and create new prevention strategies. Currently, the essential role of environmental pollutants in NAFLD development is recognized. Particularly, endocrine-disrupting chemicals (EDCs) have a notable influence. EDCs can be classified as natural (phytoestrogens, genistein, and coumestrol) or synthetic, and the latter ones can be further subdivided into industrial (dioxins, polychlorinated biphenyls, and alkylphenols), agricultural (pesticides, insecticides, herbicides, and fungicides), residential (phthalates, polybrominated biphenyls, and bisphenol A), and pharmaceutical (parabens). Several experimental models have proposed a mechanism involving this group of substances with the disruption of hepatic metabolism, which promotes NAFLD. These include an imbalance between lipid influx/efflux in the liver, mitochondrial dysfunction, liver inflammation, and epigenetic reprogramming. It can be concluded that exposure to EDCs might play a crucial role in NAFLD initiation and evolution. However, further investigations supporting these effects in humans are required.

show abstract

Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats

Cited by 58 publications

References 42 publications

Effects of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate on liver injury in Balb/c mice

Effects of bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate on liver injury in Balb/c mice

Rosmarinic acid alleviates di-2-ethylhexyl phthalate (DEHP) -induced thyroid dysfunction via multiple inflammasomes activation

Role of Endocrine-Disrupting Chemicals in the Pathogenesis of Non-Alcoholic Fatty Liver Disease: A Comprehensive Review

Contact Info

Product

Resources

About