Role of immune dysfunction in drug induced liver injury

Girish, Chandrashekaran; Sanjay, Sukumaran

doi:10.4254/wjh.v13.i11.1677

Cited by 3 publications

(3 citation statements)

References 78 publications

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“…25 However, the development of DILI involves many physiological and biochemical processes, including mitochondrial damage, oxidative stress, and immune response. [26][27][28] In addition to genes, proteins, and other macromolecules, the levels of endogenous small molecules in the body are also altered.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling of lysophosphatidylcholines in chlorpromazine hydrochloride- and N-acetyl-p-amino-phenoltriptolide-induced liver injured rats based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

et al. 2022

Hum Exp Toxicol

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Chlorpromazine hydrochloride (CH) and N-acetyl- p-amino-phenoltriptolide (APAP) are typical acentral dopamine receptor antagonists and antipyretic analgesics in clinical applications, respectively. However, it has been reported that these 2 drugs could cause liver damage. Lysophosphatidylcholines (LPCs) have multiple physiological functions and are metabolized primarily in the liver, where it undergoes significant changes when the liver is damaged. In the study, 15 LPCs in the rat serum with CH- and APAP-induced liver injury were quantified based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry, and multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA) were combined to understand CH- and APAP-induced liver injury from the perspective of LPC metabolic profiling. The quantitative results showed that there were significant changes in 10 LPCs and 5 LPCs after CH- and APAP-administration, separately. The results of PCA and OPLS-DA indicated that CH- and APAP-induced liver injury could be well distinguished by the LPC metabolic profiling, and 7 LPCs and 1 LPC biomarkers that could characterize CH- and APAP-induced liver damage in turn had been screened. This study will not only provide a new perspective for the clinical diagnosis of CH- and APAP-induced liver injury, but also offer a reference for further study of their hepatotoxicity mechanisms.

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Section: Discussionmentioning

confidence: 99%

Metabolic profiling of lysophosphatidylcholines in chlorpromazine hydrochloride- and N-acetyl-p-amino-phenoltriptolide-induced liver injured rats based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

et al. 2022

Hum Exp Toxicol

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“…They have also various functions in drug metabolism, making them considerably important in the overall mechanism of DILI. 140,141 Co-cultures that were considered in the early 2D and 3D liver models included only hepatocytes with other non-parenchymal cells randomly distributed and without compartmentalization. An example is the model of Li et al 142 in which a suspension of primary human hepatocytes and human Kupffer cells were developed and were able to detect the toxicity of 100 drug compounds with a known DILI status with more sensitivity than a conventional monoculture layer.…”

Section: Multi-compartment Modelsmentioning

confidence: 99%

“…idiosyncratic DILI -iDILI) or compounds with a low clearance rate. 140,208 Hence, the latter would not be evidenced in 2D-cultures, rendering them inadequate for hepatotoxicity prediction.…”

Section: Application Potential Of Dili Models With Increasing Complexitymentioning

confidence: 99%

The native liver as inspiration to create superior in vitro hepatic models

et al. 2023

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Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury

Sethi,

Khokhar,

Mathur

et al. 2024

Semin Liver Dis

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Drug-induced liver injury (DILI) continues to be a major concern in clinical practice, thus necessitating a need for novel therapeutic approaches to alleviate its impact on hepatic function. This review investigates the therapeutic potential of nutraceuticals against DILI, focusing on examining the underlying molecular mechanisms and cellular pathways. In preclinical and clinical studies, nutraceuticals, such as silymarin, curcumin, and N-acetylcysteine, have demonstrated remarkable efficacy in attenuating liver injury induced by diverse pharmaceutical agents. The molecular mechanisms underlying these hepatoprotective effects involve modulation of oxidative stress, inflammation, and apoptotic pathways. Furthermore, this review examines cellular routes affected by these nutritional components focusing on their influence on hepatocytes, Kupffer cells, and stellate cells. Key evidence highlights that autophagy modulation as well as unfolded protein response are essential cellular processes through which nutraceuticals exert their cytoprotective functions. In conclusion, nutraceuticals are emerging as promising therapeutic agents for mitigating DILI, by targeting different molecular pathways along with cell processes involved in it concurrently.

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Role of immune dysfunction in drug induced liver injury

Cited by 3 publications

References 78 publications

Metabolic profiling of lysophosphatidylcholines in chlorpromazine hydrochloride- and N-acetyl-p-amino-phenoltriptolide-induced liver injured rats based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

Metabolic profiling of lysophosphatidylcholines in chlorpromazine hydrochloride- and N-acetyl-p-amino-phenoltriptolide-induced liver injured rats based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

The native liver as inspiration to create superior in vitro hepatic models

Therapeutic Potential of Nutraceuticals against Drug-Induced Liver Injury

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