Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances

Golub, Aniela; Ordak, Michał; Nasierowski, Tadeusz; Bujalska‐Zadrożny, Magdalena

doi:10.3390/ijms24119413

Cited by 3 publications

(1 citation statement)

References 253 publications

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“…Diagnosis and treatment for liver diseases, including extrahepatic manifestations, have been progressing recently [28,29]. Although nucleos(t)ide analogues and direct-acting antivirals are currently available and effective for HBV and HCV-related liver diseases, more effective and more convenient drugs may be needed for hepatitis virus infection.…”

mentioning

confidence: 99%

Liver Diseases: From Bench to Bedside

Kanda,

Sasaki-Tanaka,

Terai

2024

IJMS

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mentioning

confidence: 99%

Liver Diseases: From Bench to Bedside

Kanda,

Sasaki-Tanaka,

Terai

2024

IJMS

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Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers

Balloni,

Tini,

Prospero

et al. 2024

Clinical Chemistry

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Background Approximately 30 million people worldwide consume new psychoactive substances (NPS), creating a serious public health issue due to their toxicity and potency. Drug-induced liver injury is the leading cause of liver disease, responsible for 4% of global deaths each year. Content A systematic literature search revealed 64 case reports, in vitro and in vivo studies on NPS hepatotoxicity. Maximum elevated concentrations of aspartate aminotransferase (136 to 15 632 U/L), alanine transaminase (121.5 to 9162 U/L), total bilirubin (0.7 to 702 mg/dL; 0.04 to 39.03 mmol/L), direct (0.2–15.1 mg/dL; 0.01–0.84 mmol/L) and indirect (5.3 mg/dL; 0.29 mmol/L) bilirubin, alkaline phosphatase (79–260 U/L), and gamma-glutamyltransferase (260 U/L) were observed as biochemical markers of liver damage, with acute and fulminant liver failure the major toxic effects described in the NPS case reports. In vitro laboratory studies and subsequent in vivo NPS exposure studies on rats and mice provide data on potential mechanisms of toxicity. Oxidative stress, plasma membrane stability, and cellular energy changes led to apoptosis and cell death. Experimental studies of human liver microsome incubation with synthetic NPS, with and without specific cytochrome P450 inhibitors, highlighted specific enzyme inhibitions and potential drug–drug interactions leading to hepatotoxicity. Summary Mild to severe hepatotoxic effects following synthetic NPS exposure were described in case reports. In diagnosing the etiology of liver damage, synthetic NPS exposure should be considered as part of the differential diagnosis. Identification of NPS toxicity is important for educating patients on the dangers of NPS consumption and to suggest promising treatments for observed hepatotoxicity.

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A Multiscale-Information-Embedded Universal Toxicity Prediction Framework

He,

Wu,

Wang

et al. 2024

Preprint

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The inherent toxicity of compounds poses a significant threat to human health and the environment throughout their entire lifecycle, encompassing production, use, storage, and disposal. Compound-induced toxicity evaluation is a critical concern across various fields, including drug discovery and environmental studies. Recent advances in deep learning hold promise for predicting compound-induced toxicities. However, existing works often exhibit poor predictive accuracy and generalizability, especially for rare toxicities with limited data. Most works fail to capture the three-dimensional (3D) spatial arrangement and stereochemical properties of compounds, which are crucial for understanding their toxicological profiles. And the interrelated nature of various toxicities has often been overlooked. Here we propose ToxScan, a novel SE(3)-equivariant multiscale model, as a universal toxicity prediction framework to address these issues. A two-level representation learning protocol, encompassing molecular- and atomic-level information, is introduced to better incorporate the geometry information of 3D conformation. A parallel multiscale modelling and a multi-task learning scheme is applied to learn the universal toxicological characteristics of multiple toxicity categories. Through comprehensive analysis in multiple scenarios such as multi-task toxicity prediction, module effectiveness testing, generalization testing on new small-scale endpoints, distinguishing ability on structurally similar compounds with opposing toxicities, in vitro experimental validation of new predictions, and testing on practical application data, ToxScan demonstrates convincing predictive capability and generalizability, surpassing the state-of-the-art by a remarkable 7.8–37.6% performance boost on four metrics for medium- and small-scale endpoints. Typical case studies demonstrate that ToxScan can identify subtle structural variations by capturing molecular structural features at multiple levels. To facilitate user accessibility, we have integrated the trained ToxScan and developed a user-friendly online prediction platform (https://app.bohrium.dp.tech/toxscan), allowing researchers to obtain multiple toxicity endpoint predictions for new compounds quickly and conveniently. We envision ToxScan as a valuable tool for compound-induced toxicity evaluation, effectively reducing analysis cycles and costs while providing practical utility for researchers in drug discovery, toxicology and environmental studies.

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Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances

Cited by 3 publications

References 253 publications

Liver Diseases: From Bench to Bedside

Liver Diseases: From Bench to Bedside

Exposure to Synthetic Psychoactive Substances: A Potential Cause for Increased Human Hepatotoxicity Markers

A Multiscale-Information-Embedded Universal Toxicity Prediction Framework

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