Protective effect and mechanism of chitooligosaccharides on acetaminophen-induced liver injury

Xiang, Junwei; Wang, Jin; Xie, Hong-Yi; Liu, Yongjian; Bai, Yan; Che, Qishi; Cao, Hua; Huang, Guidong; Guo, Jiao; Su, Zhixing

doi:10.1039/d1fo00953b

Cited by 18 publications

(11 citation statements)

References 32 publications

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“…Several intervention studies confirmed that TNF expression alters the severity of AILI [ 89 , 166 , 191 , 226 , 227 ]. Combination therapy of boldine and NAC significantly reduces the expression of inflammatory markers, including TNF-α, IL-1β, and IL-6 [ 228 ].…”

Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 98%

“…Plentiful clinical and experimental animal data indicate that IL-6 is highly induced in AILI and inhibiting IL-6 expression by multiple interventions can significantly alleviate the liver injury caused by APAP. All these studies suggest that IL-6 plays a considerable role in promoting the inflammatory response process in AILI [ 72 , 175 , 177 , 191 , 192 ]. However, a few contrary reports suggest that IL-6 deficient mice lacking the expression of cytoprotective heat shock proteins (HSPs) would be more susceptible to APAP hepatotoxicity [ 193 ].…”

Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 99%

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The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

Chen

Wang

2022

Cell Biosci

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Acute liver failure caused by drug overdose is a significant clinical problem in developed countries. Acetaminophen (APAP), a widely used analgesic and antipyretic drug, but its overdose can cause acute liver failure. In addition to APAP-induced direct hepatotoxicity, the intracellular signaling mechanisms of APAP-induced liver injury (AILI) including metabolic activation, mitochondrial oxidant stress and proinflammatory response further affect progression and severity of AILI. Liver inflammation is a result of multiple interactions of cell death molecules, immune cell-derived cytokines and chemokines, as well as damaged cell-released signals which orchestrate hepatic immune cell infiltration. The immunoregulatory interplay of these inflammatory mediators and switching of immune responses during AILI lead to different fate of liver pathology. Thus, better understanding the complex interplay of immune cell subsets in experimental models and defining their functional involvement in disease progression are essential to identify novel therapeutic targets for the treatment of AILI. Here, this present review aims to systematically elaborate on the underlying immunological mechanisms of AILI, its relevance to immune cells and their effector molecules, and briefly discuss great therapeutic potential based on inflammatory mediators.

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Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 98%

Section: Role Of Inflammatory Mediators In Ailimentioning

confidence: 99%

The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

Chen

Wang

2022

Cell Biosci

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“…[7] Inhibiting or deleting CYP2E1 has been shown to effectively reduce the production of NAPQI, block ROS production, and alleviate inflammation in APAP-induced mouse models. [11][12][13] Therefore, this approach has the potential to be a useful therapy in treating APAP-induced ALF. 18𝛽-Glycyrrhetinic acid (18𝛽-GA), a in vivo metabolic component of glycyrrhiza acid while is commonly used as a liver protection drug in clinic, is reported to be a potent inhibitor of CYP2E1, [14] indicating that 18𝛽-GA could be a candidate for ALF treatment.…”

Section: Introductionmentioning

confidence: 99%

A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS

Yao

Tang

Dai

et al. 2023

Adv Healthcare Materials

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Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N‐acetyl‐p‐benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N‐acetylcysteine is the Food and Drug Administration‐approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration‐related adverse effects. In this study, a carrier‐free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18β‐Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2‐related factor 2/heme oxygenase‐1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half‐life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.

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“…N ‐acetyl‐L‐cysteine (NAC), a precursor of GSH, is currently the only drug employed for the clinical detoxification of APAP‐induced hepatotoxicity 12,13 . However, its application is limited owing to its narrow therapeutic window and numerous serious side effects 14,15 . Therefore, developing more effective treatment strategies with fewer side effects is urgently required.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 However, its application is limited owing to its narrow therapeutic window and numerous serious side effects. 14,15 Therefore, developing more effective treatment strategies with fewer side effects is urgently required.…”

mentioning

confidence: 99%

Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

Zhai

Dai

Chi

et al. 2022

Environmental Toxicology

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Severe acetaminophen (APAP)-induced hepatic damage is the second most common cause for hepatic transplantation. Clinically, hepatic damage caused by APAP is treated using N-acetyl-L-cysteine, which can induce numerous side effects. Naringin, a bioflavonoid abundant in grapefruit and other citrus fruits, displays marked antiinflammatory and antioxidant activities. Herein, we aimed to investigate the potential mechanism underlying naringin-mediated protection against APAP-induced acute hepatotoxicity. We observed that naringin afforded protection against APAPinduced acute liver failure in mice. Importantly, pretreatment with naringin before APAP administration further increased antioxidant enzyme expression, inhibited the production of proinflammatory cytokines, and activated apoptotic pathways. Furthermore, we observed that the protective effect was associated with the upregulation of cation transport regulator-like protein 2 (CHAC2) and nuclear factor erythroid derived-2-related factor 2 (Nrf2). Notably, CHAC2 knockdown inhibited Nrf2 activation and naringin-mediated antioxidant, antiinflammatory, and antiapoptotic effects in APAP-induced liver injury. Likewise, si-Nrf2 blocked the protective effect of naringin against APAP-induced liver injury. Collectively, our results indicate that naringin may be a potent CHAC2 activator, alleviating APAP-induced hepatitis via CHAC2-mediated activation of the Nrf2 pathway. These data provide new insights into mechanisms through which CHAC2 regulates APAP-induced liver injury by targeting Nrf2, which should be considered a novel therapeutic target.

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Protective effect and mechanism of chitooligosaccharides on acetaminophen-induced liver injury

Abstract: Currently, drug-induced liver injury caused by acetaminophen (APAP) is the second leading cause of human liver transplantation. The only clinical antidote treatment for APAP-induced liver injury is N-acetyl-L-cysteine (NAC), which...

Cited by 18 publications

References 32 publications

The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity

A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS

Naringin alleviates acetaminophen‐induced acute liver injury by activating Nrf2 via CHAC2 upregulation

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