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Open research questions in Drug-Induced Hepatotoxicity and Protection

48 unresolved questions extracted from the limitations and future-work sections of 657 Drug-Induced Hepatotoxicity and Protection papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Further studies on bioavailability issu- es and mechanisms of activity may enable the development of effective and safe alternative approaches to reduce side effects, such as liver damage encountered during isotretinoin treat- ment, and help hesperidin to be used more wi- dely for therapeutic applications.

    FLAVONOID-BASED APPROACH TO HEPATIC DAMAGE INDUCED BY RETINOID DERIVATIVES: INVESTIGATION OF THE EFFECTS OF HESPERIDIN · 2026 · DOI

  • <br /> <b>Conclusion: </b>Both extracts, especially at higher doses, appeared chemoprotective against DEN-induced hepatic changes, supporting further investigation of their underlying mechanisms.

    Effect of Aqueous Extracts of <i>Kigelia africana</i> and <i>Acacia nilotica</i> on Selected Tumour Markers in Diethylnitrosamine-Induced Liver Cell Dysplasia in Wistar Rats · 2026 · DOI

  • Comparisons between ATS and BTS protocols have yielded conflicting results, with no definitive advantage demonstrated for either approach. However, current evidence remains inconsistent and insufficient to establish superiority.

    Reintroducing antitubercular therapy after drug-induced liver injury: A narrative review of protocols · 2026 · DOI

  • Second, because the study population consisted exclusively of Chinese participants, the applicability of these results to other ethnic groups remains to be established. is warranted Data availability statement The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

    Pharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment · 2026 · DOI

  • The clinical presentation of DILI varies widely, ranging from an asymptomatic rise in liver enzymes to liver failure. Although urgent administration of an immunosuppressive agent remains controversial for SMS-induced DILI, histological changes in Patient 1 demonstrated that the patient can benefit from methylprednisolone.

    Methylprednisolone for Swietenia macrophylla seeds-induced liver injury: A case report · 2026 · DOI

  • This report expands the limited literature on acetaminophen toxicity in premature neonates and emphasizes the growing importance of understanding neonatal pharmacokinetics as acetaminophen use in neonatal intensive care units increases, particularly for treatment of hemodynamically significant patent ductus arteriosus (PDA).

    Acetaminophen Overdose in an Extremely Low-Birth-Weight Premature Infant: A Case Report and Review of the Literature · 2026 · DOI

  • According to OECD conducted in mice, in which blood sampling guideline 423, an herbal formulation containing is typically limited to a single time point, Anethum graveolens, Cynara scolymus, Citrus precluding time-course analysis of biochemical aurantium, Portulaca oleracea, and Silybum parameters.

    Evaluating acute toxicity and hepatoprotective effect of Ich can thanh oral solution in a paracetamol-induced acute hepatitis mouse model · 2026 · DOI

  • Second, target selectivity remains to be fully characterized. instead of modulating mitophagy, to reduce AA production and lipogenesis, DCA-C directly Several limitations of this study should be acknowledged.

    Dicaffeoylquinic acid alleviates alcoholic liver disease by targeting PLA2G4B and inhibiting the MAPK signaling pathway · 2026 · DOI

  • In addition, while conventional statistical methods have inherent non-linear in modeling relationships and integrating high-dimensional data, machine learning (ML) offers a powerful for capturing such complexity and improving risk prediction (Sidey-Gibbons and Sidey-Gibbons, 2019; Topol, 2019). Beyond prediction, mediation analysis can be used to assess whether observed genetic associations with hepatotoxicity are statistically mediated, in part, by measured exposure variables. Importantly, such analyses do not by themselves establish a direct biological mechanism. tool Accordingly, this study establishes a prospective cohort of pediatric tuberculosis patients in China with the following objectives (Zhou et al., 2025): to systematically screen key single nucleotide polymorphisms (SNPs) potentially associated with ATB- DILI in children, a population less frequently represented in pharmacogenetic studies (Marais, 2014); to explore, using causal mediation analysis, whether the association between genetic variation and hepatotoxicity may be statistically mediated, in part, by measured isoniazid plasma concentration in pediatric populations; and (Mehra et al., 2022) to develop and evaluate machine learning-based predictive models integrating multimodal data, and to assess whether incorporating genetic markers could offer additional value for risk prediction. By addressing these aspects, this study aims to identify children at increased risk of informing personalized monitoring and ATB-DILI, preventive strategies in pediatric tuberculosis treatment.

    NAT2 rs1495741 and anti-tuberculosis drug-induced liver injury in children: genetic association and risk prediction · 2026 · DOI

  • The study does not compare curcumin's hepatoprotective efficacy directly with the conventional antidote N-acetylcysteine (NAC) in the same experimental design.

    Hepatoprotectıve Property Of Turmeric (Curcumin) Administration On Chronic Acetaminophen Induced Liver Damage In Albino Wistar Rats · 2026 · DOI

  • The mechanisms by which curcumin inhibits cytochrome P450 enzymes and prevents NAPQI formation require further detailed investigation beyond the study's scope.

    Hepatoprotectıve Property Of Turmeric (Curcumin) Administration On Chronic Acetaminophen Induced Liver Damage In Albino Wistar Rats · 2026 · DOI

  • Despite more than a decade of research, other than direct damage to hepatocytes caused by inhibition of cellular DNA synthesis and resulting in hepatocyte necrosis, the rest of the specific mechanisms remain unclear, and few effective solutions are available.

    Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs) · 2024 · DOI

  • PIC prevents Hz-induced hyperlipidemia, hepatic steatosis, and mobilization of lipids from depot fats, but the mechanism behind the protective effect of PIC remains to be elucidated.

    Protective Effect of Picroliv Against Hydrazine-Induced Hyperlipidemia and Hepatic Steatosis in Rats · 2007 · DOI

  • Fomepizole, a CYP2E1 inhibitor, reduces NAPQI when co‐administered with acetaminophen, but its clinical relevance remains uncertain.

    Effects of Fomepizole on Acetaminophen Oxidative Metabolism: A Randomized, Crossover Study in Human Volunteers · 2026 · DOI

  • The early failure pattern suggests that hepatic events may tend to occur relatively early after treatment initiation, which highlights the importance of baseline assessment and early-phase monitoring, but continued clinical vigilance remains warranted.

    Hepatic Adverse Event Signals of Fezolinetant in Real-World Use Based on Postmarketing Surveillance · 2026 · DOI

  • These pioneering findings suggest that PSE-PMLs are a promising prophylactic agent against ALF, warranting further studies in the post-injury models.

    α-Linolenic acid-driven nano-liposomes from purslane seed oil modulate p-JAK2/p-STAT3 to combat acute liver failure · 2026 · DOI

  • Curcumin's low bioavailability has characterized it as a weak and impractical drug due to its poor absorption, poor solubility as well as its rapid elimination and clearance from the body.

    Hepatoprotectıve Property Of Turmeric (Curcumin) Administration On Chronic Acetaminophen Induced Liver Damage In Albino Wistar Rats · 2026 · DOI

  • Although exact mechanism of action of risperidone on liver remains unknown, there are growing evidences that link alterations of fatty acid biosynthesis to hepatic adverse effects.

    Risperidone and Hepatotoxicity in Children and Adolescent: A Literature Review · 2020 · DOI

  • Even though NAC is an excellent antidote, its effectiveness is limited to the first 16 hours following overdose.

    The development and hepatotoxicity of acetaminophen: reviewing over a century of progress · 2020 · DOI

  • Considering the limited data about the influence of palladium on the cardiovascular system, the aim of our study was to evaluate the effects of palladium on the heart from available published data, and to compare the toxicity of inorganic and organic palladium compounds.

    Cardiotoxicity of Palladium Compounds / Kardiotoksičnost Jedinjenja Paladijuma · 2012 · DOI

  • It remains to be determined why diazepam and oxazepam induce CYP4A in mice but not rats and whether this difference accounts for the apparent species difference in the tumor-promoting activity of diazepam and oxazepam.

    On the Mechanism of Hepatocarcinogenesis of Benzodiazepines: Evidence that Diazepam and Oxazepam are CYP2B Inducers in Rats, and both CYP2B and CYP4A Inducers in Mice · 2006 · DOI

  • <i>Thymus quinquecostatus</i> Celak is a food additive and an edible herb that is widely used in Asia and possesses hepatoprotective activity, but the underlying mechanisms behind this protective activity are not completely understood.

    Prikaz knjiga: 'Mape uma' i 'Savršeno pamćenje' Tonija Buzana - Brzo čitanje: iluzija, talenat ili veština koja se uči - Finesa, Beograd, 1999. · 1999 · DOI

  • The importance of dose timing has not been evaluated for adrenergic potentiation of methylphenidate hepatotoxicity, but it is clear that this interaction is based on yet a third mechanism.

    Adrenergic Modulation of Hepatotoxicity · 1997 · DOI

  • The importance of 58-ABP arylation with early, apparently selective, translocation to the nucleus remains to be elucidated.

    Selective Protein Arylation and Acetaminophen-Induced Hepatotoxicity · 1997 · DOI

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48 open questions have been extracted from the limitations and future-work passages of 657 Drug-Induced Hepatotoxicity and Protection papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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