A study on the protective effects of taxifolin on human umbilical vein endothelial cells and THP-1 cells damaged by hexavalent chromium: a probable mechanism for preventing cardiovascular disease induced by heavy metals

Cao, Xiangyu; Bi, Ruochen; Hao, Jianli; Wang, Shuai; Huo, Yapeng; Demoz, Rahewa Mahir; Banda, Ruth; Tian, Siqi; Xin, Chong; Fu, Mingyang; Pi, Jingwen; Liu, Jianli

doi:10.1039/d0fo00567c

Cited by 25 publications

(17 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Son et al have also reported that Cr(VI) treatment could induce JB6 murine epidermal cells apoptosis by up‐regulation of JNK signaling 36 . Similarly, Cao et al have also showed that Cr(VI) exposure could increase the phosphorylation of p38 and JNK, which regulated the expression of Bax and Bcl‐2 in human umbilical vein endothelial cells 37 . Taken together, these studies well support the results of our experiment, that is, ROS induced by Cr(VI) promotes the activation of JNK pathway.…”

Section: Discussionmentioning

confidence: 92%

Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling

Jin

Kom

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

With the spread of hexavalent chromium (Cr(VI)) contamination, Cr(VI)-induced hepatotoxicity has attracted increasing attention in recent years. To date, however, the exact mechanism of Cr(VI) toxicity remains unclear. In this study, we investigated the role of apoptosis signal-regulating kinase 1 (ASK1)/c-Jun aminoterminal kinase (JNK) in Cr(VI)-induced hepatic toxicity and the possible related mechanisms. AML-12 hepatocyte cell-lines were treated with 0, 1, 4, and 16 μmol/Lof Cr(VI) with or without GS-444271 (an ASK1 inhibitor). Adult male mice were administered with 0, 2, 8, and 32 mg/kg body mass (BM)/day of Cr(VI) for 5 days. The level of hepatocyte apoptosis/proliferation, generation of reactive oxygen species (ROS), and expression levels of mRNAs and proteins related to ASK1/JNK and nuclear factor-E2-related factor 2 (Nrf2) signaling were assessed. Results showed that high Cr(VI) exposure induced hepatocyte apoptosis and liver injury by generation of ROS and down-regulation of Nrf2 signaling. In addition, ASK1/JNK signaling activity was upregulated in the Cr(VI)-treated group. Furthermore, GS-444217 treatment significantly rescued Cr(VI)-induced hepatocyte apoptosis and liver dysfunction in vitro and in vivo by down-regulation of ASK1/JNK signaling. Thus, ASK1/JNK signaling appears to play an important role in Cr(VI)-induced hepatocyte apoptosis and liver injury. This study should help improve our understanding of the mechanism of Cr(VI)-induced liver injury and provide support for future investigations on liver disease therapy.

show abstract

Section: Discussionmentioning

confidence: 92%

Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling

Jin

Kom

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

show abstract

“…On the one hand, SREBP-1 plays and progression of HCC and is an ideal intervention target for HCC treatment. Small molecule inhibitors are an ideal mode of action for specific targets (71)(72)(73)(74). The existing SREBP-1 small molecule inhibitors are mainly Betulin, Pseudoprotodioscin and Fatostatin (75)(76)(77).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

2021

View full text Add to dashboard Cite

Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

show abstract

“…There is much evidence showing that the major inflammatory cytokines during this process are the IL-1 family ( Carty et al, 2009 ; Herder et al, 2017 ; Pfeiler et al, 2019 ), IL-6 ( Carty et al, 2009 ; Prochnau et al, 2012 ; Morieri et al, 2017 ), IL-17 ( Madsen et al, 2016 ), IL-18 ( Buraczynska et al, 2016 ; Lee et al, 2019 ), IL-32 ( Damen et al, 2017 ), TNF-α ( Singh et al, 2005 ; Shen et al, 2016 ), C-reactive protein (CRP) ( Chiang et al, 2019 ; Martin-Nunez et al, 2020 ). Adhesion Molecules are also very important, such as vascular cell adhesion molecule-1 (VCAM-1) ( Denys et al, 2016 ; Kunutsor et al, 2017 ; Cao et al, 2020 ; Yari et al, 2020 ), intercellular adhesion molecule-1 (ICAM-1) ( Cao et al, 2020 ; Yari et al, 2020 ), and platelet endothelial cell adhesion molecule-1 (PECAM-1) ( Stevens et al, 2008 ). SGLT-2 inhibitors are recognized as effective agents for decreasing these inflammatory factors.…”

Section: Sglt-2 Inhibitors Improve Diabetic Cardiovascular Diseases B...mentioning

confidence: 99%

Emerging Roles of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors in Diabetic Cardiovascular Diseases: Focusing on Immunity, Inflammation and Metabolism

et al. 2022

View full text Add to dashboard Cite

Diabetes mellitus (DM) is one of the most fast evolving global issues characterized by hyperglycemia. Patients with diabetes are considered to face with higher risks of adverse cardiovascular events. Those are the main cause of mortality and disability in diabetes patients. There are novel antidiabetic agents that selectively suppress sodium-glucose cotransporter-2 (SGLT-2). They work by reducing proximal tubule glucose reabsorption. Although increasing evidence has shown that SGLT-2 inhibitors can contribute to a series of cardiovascular benefits in diabetic patients, including a reduced incidence of major adverse cardiovascular events and protection of extracardiac organs, the potential mechanisms of SGLT2 inhibitors’ cardiovascular protective effects are still not fully elucidated. Given the important role of inflammation and metabolism in diabetic cardiovascular diseases, this review is intended to rationally compile the multifactorial mechanisms of SGLT-2 inhibitors from the point of immunity, inflammation and metabolism, depicting the fundamental cellular and molecular processing of SGLT-2 inhibitors exerting regulating immunity, inflammation and metabolism. Finally, future directions and perspectives to prevent or delay cardiovascular complications in DM by SGLT-2 inhibitors are presented.

show abstract

A study on the protective effects of taxifolin on human umbilical vein endothelial cells and THP-1 cells damaged by hexavalent chromium: a probable mechanism for preventing cardiovascular disease induced by heavy metals

Abstract: Taxifolin suppressed the toxicity and THP-1 cell adhesion to HUVECs induced by Cr(vi) via regulating the p38 MAPK and JNK pathways.

Cited by 25 publications

References 56 publications

Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling

Hexavalent chromium induces hepatocyte apoptosis via regulation of apoptosis signal‐regulating kinase 1/c‐Jun amino‐terminal kinase signaling

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

Emerging Roles of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitors in Diabetic Cardiovascular Diseases: Focusing on Immunity, Inflammation and Metabolism

Contact Info

Product

Resources

About