Tert-Butylhydroquinone Protects Liver Against Ischemia/Reperfusion Injury in Rats Through Nrf2-Activating Anti-Oxidative Activity

Zeng, Xianpeng; Li, X.-J.; Zhang, Q.-Y.; Liu, Qi; Li, L.; Xiong, Yan; He, Chunmei; Wang, Y.-F.; Ye, Q.-F.

doi:10.1016/j.transproceed.2016.12.008

Cited by 29 publications

(14 citation statements)

References 20 publications

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“…The transcription factor NRF2 plays important roles in maintenance of cellular redox homeostasis and antitumor processes [43]. Recent research has indicated that the promoter region of the NRF2 gene contains PPREs; therefore, PPARγ could bind to these PPREs in the NRF2 promoter, enabling activation of the NRF2 gene and upregulating the expression of various antioxidant genes [44,45].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

Zhou

Peng

Jiang

et al. 2020

Preprint

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Background Astrocytes mediate brain defense against oxidative stress-induced injury. Silent information regulator 1 (SIRT1) has anti-oxidative stress effects in many diseases and is highly expressed in astrocytes. However, the neuroprotective effects of SIRT1 on astrocytes after cerebral ischemia/reperfusion injury are unclear. Methods Here, we evaluated the effects of SIRT1 in astrocytes after cerebral ischemia/reperfusion injury using oxygen-glucose deprivation/recovery in astrocytes in vitro and middle cerebral artery occlusion in rats in vivo. Results SIRT1 knockdown reduced cell viability, increased oxidative stress, and decreased peroxisome proliferator activated receptor (PPAR)-γ coactivator (PGC)-1α, PPARγ, nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase (HO)-1, and NAD(P)H:quinone oxidoreductase-1 (NQO1) expression. Moreover, SIRT1 knockdown also suppressed PGC-1α activity, the PGC-1α/PPARγ interaction, and the PPARγ/peroxisome proliferator-response element (PPRE) interaction. Similarly, in our in vivo experiments, SIRT1 overexpression and PGC-1α or PPARγ knockdown reduced PGC-1α, PPARγ, NRF2, HO-1, and NQO1 protein expression and blocked the PGC-1α/PPARγ interaction. SIRT1 overexpression plus PPARγ knockdown inhibited the interaction of PPARγ with PPRE. NRF2 knockdown blocked NRF2 expression and downstream proteins induced by SIRT1 overexpression. Conclusion Overall, our data indicated that SIRT1 directly mediated the PGC-1α/PPARγ pathway in response to focal cerebral ischemia/reperfusion-induced neurological deficit, providing insights into the treatment of focal cerebral ischemia/reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

Zhou

Peng

Jiang

et al. 2020

Preprint

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“…The dose of DOX used in this study was reported to induce oxidative stress and nephrotoxicity in rats 55 , and is equivalent to 42 mg/m 2 human dose, which is within the often prescribed clinically effective dose range of 40–75 mg/m 2 every 3–4 weeks 56 . On the other hand, the dose of tBHQ used in the present study has been reported to activate cytoprotective genes in rat models of oxidative injury 29 , 57 .…”

Section: Methodsmentioning

confidence: 51%

Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats

Ujah

Nna

Suleiman

et al. 2021

Sci Rep

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Doxorubicin (DOX) is a broad-spectrum chemotherapeutic drug used in the treatment of cancers. It acts by generating reactive oxygen species in target cells. The actions are, however, not limited to cancerous cells as it attacks healthy cells, killing them. This study investigated the benefits of the antioxidant, tert-butylhydroquinone (tBHQ), on testicular toxicity following DOX therapy. Twenty-four adult male albino rats were assigned randomly into four groups (n = 6), namely: normal control (NC), tBHQ, DOX and tBHQ + DOX groups. tBHQ (50 mg/kg body weight in 1% DMSO) was administered orally for 14 consecutive days, while a single DOX dose (7 mg/kg body weight) was administered intraperitoneally on Day 8. DOX decreased sperm count, motility and viability, and decreased the levels of steroidogenesis-related proteins, and reproductive hormones. Furthermore, DOX decreased the expression of antioxidant cytoprotective genes, and decreased the protein level of proliferating cell nuclear antigen in the testis. Conversely, DOX increased the expression of pro-inflammatory and pro-apoptotic genes in the testis. These negative effects were ameliorated following the intervention with tBHQ. Our results suggest that tBHQ protects the testis and preserves both steroidogenesis and spermatogenesis in DOX-treated rats through the suppression of oxidative stress, inflammation and apoptosis.

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“…Previous studies have suggested a role of Nrf2 in antioxidative and anti-apoptotic process functions in IRI ( 16 , 47 ). Therefore, the present study proposed that the activity of Nrf2 may serve a role in the protective effects of HMP against IRI; the protein and mRNA expression levels of Nrf2 between the HMP and CS groups were investigated.…”

Section: Discussionmentioning

confidence: 95%

Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway

Xue

Zeng

et al. 2018

Mol Med Report

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Hypothermic machine perfusion (HMP) has been demonstrated to be a more effective method for preserving livers donated after circulatory death (DCD) than cold storage (CS); however, the underlying mechanisms remain unclear. The aim of the present study was to investigate the protective effects of HMP on rat DCD livers and the possible role of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. A total of 18 adult male rats were randomly divided into three groups: Control, HMP and CS (n=6 per group). To simulate the conditions of DCD liver transplantation, rat livers in the CS and HMP groups were subjected to 30 min warm ischemia following cardiac arrest and were then preserved by CS or HMP for 3 h. Subsequently, after 1 h of isolated reperfusion, the extent of ischemia/reperfusion injury (IRI) and cellular functions were assessed. During reperfusion, intrahepatic resistance and bile production were measured, and the perfusion fluid was collected for liver enzyme analysis. The liver tissues were then harvested for the assessment of malondialdehyde (MDA) production, superoxide dismutase (SOD) activity, ATP levels, as well as for histological analysis, immunohistochemistry and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Finally, the expression levels of the components associated with the Nrf2-ARE signaling pathway were analyzed via western blotting and reverse transcription-quantitative polymerase chain reaction. The results of the present study revealed that, compared with in the CS group, the HMP group exhibited higher levels of ATP, bile production and SOD activity, and improved histological results; however, lower levels of liver enzymes, apoptosis and MDA were detected. Additionally, the findings of the present study also suggested that the Nrf2-ARE signaling pathway may be activated by the steady laminar flow of HMP. In conclusion, HMP may attenuate ischemia-reperfusion injury to rat DCD livers via activation of the Nrf2-ARE signaling pathway.

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Tert-Butylhydroquinone Protects Liver Against Ischemia/Reperfusion Injury in Rats Through Nrf2-Activating Anti-Oxidative Activity

Cited by 29 publications

References 20 publications

WITHDRAWN: Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

WITHDRAWN: Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

Tert-butylhydroquinone attenuates doxorubicin-induced dysregulation of testicular cytoprotective and steroidogenic genes, and improves spermatogenesis in rats

Hypothermic machine perfusion attenuates ischemia/reperfusion injury against rat livers donated after cardiac death by activating the Keap1/Nrf2‑ARE signaling pathway

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