Geniposide protected hepatocytes from acetaminophen hepatotoxicity by down-regulating CYP 2E1 expression and inhibiting TLR 4/NF-κB signaling pathway

Yang, Sen; Kuang, Ge; Jiang, Rong; Wu, Shengwang; Zeng, Tao; Wang, Yuanyuan; Xu, Fangzhi; Xiong, Lingyi; Gong, Xia; Wan, Jingyuan

doi:10.1016/j.intimp.2019.05.010

Cited by 33 publications

(18 citation statements)

References 39 publications

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“…Recent studies indicate that an acute bolus dose or chronic administration of APAP increases the level of CYP2E1 expression. [ 35,36 ] Consistent with these reports, our results showed upregulation of hepatic CYP2E1 content that reflects aggravated liver injury in APAP‐intoxicated mice. This upregulation of CYP2E1 expression can be explained by the binding of APAP to the active site of CYP2E1 protects the protein from degradation, allowing it to accumulate as a consequence of unaltered synthesis.…”

Section: Discussionsupporting

confidence: 91%

Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice

Helal

Samra

2020

J Biochem & Molecular Tox

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Hepatotoxicity induced by acetaminophen (APAP)-overdose is a major concern in clinical practice. In the present work, the detoxifying effect of irbesartan (Irb) on the APAP-induced acute liver injury was evaluated in mice. Induction of acute liver injury in mice was established by a single intraperitoneal (IP) injection of APAP (0.5 g/kg), then mice were injected with Irb (50 or 75 mg/kg, IP), each given twice at 1 and 12 hours post APAP injection. Liver functions, hepatic oxidative and nitrosative stress markers, and liver histopathology were determined after 24 hours. Hepatic cytochrome P450 2E1 (CYP2E1), nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), caspase-3, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) levels were also estimated. Immunohistochemical evaluations of hepatic expression of phosphorylated NF-kB and active caspase-3 were assigned. Irb treatment attenuated APAP-induced acute liver injury. Irb suppressed APAP-caused elevation of liver enzymes as well as oxidative and nitrosative stress in liver tissues as evidenced by the decrease in hepatic CYP2E1 expression and hepatic levels of malondialdehyde and nitric oxide in addition to the elevated hepatic superoxide dismutase activity and reduced glutathione concentration. Also, Irb mitigated APAP-induced inflammation in liver tissues via decreasing the expression of hepatic NF-κB, phosphorylated NF-κB and TNF-α, and attenuated hepatic apoptosis via decreasing Bax/Bcl-2 ratio and caspase 3 expression and activation. Also, Irb mitigated the APAP-induced histopathological changes in liver specimens. These data suggested that Irb ameliorates APAP-induced acute liver injury through antioxidant, anti-inflammatory, and antiapoptotic activities.

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Section: Discussionsupporting

confidence: 91%

Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice

Helal

Samra

2020

J Biochem & Molecular Tox

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“…In APAP-induced hepatic injury, oxidative stress causes the activation of in ammatory related-signaling pathways, which further aggravates liver injury [44]. NLRP3 has been considered as an important proin ammatory factor activated by oxidative stress [45,46].…”

Section: Discussionmentioning

confidence: 99%

Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

et al. 2021

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“…The AMPK/ Nrf2 signalling pathway can regulate lipid metabolism in liver disturbance 17 . Meanwhile, chronic inflammatory responses such as the ones associated with liver disturbance have been shown to be closely connected with the TLR‐4/ NF‐κB signalling pathway 12 . In this study, C57BL/6J mice were fed a HFD to establish a liver disturbance model and evaluate the effect of DCP on liver function, glycolipid metabolism, oxidative stress and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR‐4/NF‐κB and AMPK/Nrf2 signalling pathways

Zhang

Gao

et al. 2020

J Cellular Molecular Medi

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The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate–activated protein kinase/ nuclear factor erythroid 2‐related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll‐like receptor 4 (TLR‐4)/ nuclear factor kappa‐B (NF‐κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR‐4 knockout (−/−) mice. For this, we evaluated the expression levels of SREBP‐1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR‐4/ NF‐κB inflammatory pathway, DCP inhibits TLR‐4, up‐regulates the expression of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), reduces the expression of phospho(p)‐NF‐κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up‐regulates the expression of p‐AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.

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Geniposide protected hepatocytes from acetaminophen hepatotoxicity by down-regulating CYP 2E1 expression and inhibiting TLR 4/NF-κB signaling pathway

Cited by 33 publications

References 39 publications

Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice

Irbesartan mitigates acute liver injury, oxidative stress, and apoptosis induced by acetaminophen in mice

Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway

Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR‐4/NF‐κB and AMPK/Nrf2 signalling pathways

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