Hepatotoxicity Research Articles

S4684 Rare Case of Drug-Induced Liver Injury Secondary to Benadryl Use

S4684 Rare Case of Drug-Induced Liver Injury Secondary to Benadryl Use

Severe acute liver disease in adults: Contemporary role of histopathology.

Liver biopsies have consistently contributed to our understanding of the pathogenesis and aetiologies of acute liver disease. As other diagnostic modalities have been developed and refined, the role of biopsy in the management of patients with acute liver failure (ALF), acute-on-chronic liver failure (ACLF) and acute hepatitis, including acute liver injury (ALI), has changed. Liver biopsy remains particularly valuable when first-line diagnostic algorithms fail to determine aetiology. Despite not being identified as a mandatory diagnostic tool in recent clinical guidelines for the management of ALF or ACLF, many centres continue to undertake biopsies given the relative safety of transjugular biopsy in this setting. Several studies have demonstrated that liver biopsy can provide prognostic information, particularly in the context of so-called indeterminate hepatitis, and is extremely useful in excluding conditions such as metastatic tumours that would preclude transplantation. In addition, its widespread use of percutaneous biopsies in cases of less severe acute liver injury, for example in the establishment of a diagnosis of acute presentation of autoimmune hepatitis or confirmation of a probable or definite drug-induced liver injury (DILI), has meant that many centres have seen a shift in the ratio of specimens they are receiving from patients with chronic to acute liver disease. Histopathologists therefore need to be equipped to deal with these challenging specimens. This overview provides an insight into the contemporary role of biopsies (as well as explant and autopsy material) in diagnosing acute liver disease. It outlines up-to-date clinical definitions of liver injury and considers recent recommendations for the diagnosis of AIH and drug-induced, autoimmune-like hepatitis (DI-AIH).

S4449 Severe Drug-Induced Liver Injury Due to RAD-140 Use

S4449 Severe Drug-Induced Liver Injury Due to RAD-140 Use

Dual anti-inflammatory effects of curcumin and berberine on acetaminophen-induced liver injury in mice by inhibiting NF-κB activation via PI3K/AKT and PPARγ signaling pathways

Acetaminophen (APAP) overdose is still a leading cause of drug-induced liver injury (DILI), accompanied with severe inflammatory response. However, the therapy for APAP-induced DILI is rather limited. The combined application of natural products to treat DILI induced by APAP may be a new direction of the research. This study was conducted to evaluate the dual anti-inflammatory activity of curcumin (CUR) combined with berberine (BBR) against APAP-mediated DILI. Network pharmacology found that PI3K-Akt and PPAR signaling pathways were primarily involved in anti-DILI of the combination of CUR and BBR. APAP injection enhanced the levels of ALT, AST, IL-1β, IL-6, and TNF-α in mice, while such phenomenon was significantly reversed by the cotreatment of CUR and BBR, which was more effective than either single treatment. The increase of p-NF-κB and p-IKKα/β protein expression and the decrease of p-PI3K, p-AKT, and PPARγ protein expression in APAP-treated mice were markedly inhibited by the coadministration of CUR and BBR. Molecular docking further demonstrated that both CUR and BBR could stably bind to PI3K, AKT, and PPARγ protein. In conclusion, the combination of CUR and BBR more effectively protected liver from APAP-triggered DILI than individual treatment. The mechanism is to alleviate hepatic inflammation by inhibiting NF-κB activation, which is possibly mediated by PI3K/Akt and PPARγ signaling pathways.

Vitamin C Intake and Anti-Tuberculosis Drugs-Induced Hepatitis in Pulmonary Tuberculosis Patients

Introduction: Drug-induced hepatitis (DIH) is one of the serious side effects of anti-tuberculosis drugs (ATD) that can reduce patient compliance with tuberculosis (TB) treatment, increase the risk of treatment failure, or develop drug resistance. Vitamin C is a potential antioxidant known to have a protective effect against DIH. This study examined the relationship between vitamin C intake and the incidence of ATD-induced hepatitis (ATDIH) in pulmonary TB patients at Persahabatan National Respiratory Referral Hospital, Jakarta. Methods: This was a cross-sectional study of 108 patients with drug-sensitive pulmonary TB. Data was collected using a sociodemographic questionnaire, anthropometric measurements, semi-quantitative food frequency questionnaire (SQ FFQ), and data on the subject's liver function laboratory results in the last 1 month. Fisher exact test was utilized to analyze the association between adequacy of vitamin C intake and DIH. Results: The proportion of DIH in pulmonary TB patients in this study was 6.5%. Most subjects were males (54.6%) with a median age of 41. The median vitamin C intake was 66.65 mg/day, with 63.0% of patients having an intake below the recommendation. Fisher's exact test showed that vitamin C intake was not statistically significantly associated with the incidence of ATDIH (OR 3.77 95% CI 0.44-32.55, p-value 0.256). No factors also influenced the incidence of ATDIH in this study. Conclusion: No association was found between vitamin C intake and other factors related to the incidence of ATDIH. This is the first study in Indonesia to link vitamin C and E intake with the incidence of DIH in drug-sensitive pulmonary TB patients, providing information for future studies.

Therapeutic potential of Shaoyao Gancao Decoction in mitigating anti-tuberculosis drug-induced liver injury through Nrf-2/HO-1/NF-κB signaling.

Tuberculosis (TB) is a persistent global health issue, evidenced by an increasing number of cases. Although anti-TB drugs have proven efficacy, they are often associated with severe liver injury (ATB-DILI). The objective of this research was to uncover the mechanisms through which Shaoyao Gancao Decoction (SGD) mitigates ATB-DILI, emphasizing the role of the Nrf-2/HO-1/NF-κB signaling pathway. We prepared SGD granules and subjected them to HPLC-MS/MS for analysis. An ATB-DILI rat model was then developed and administered SGD. We evaluated liver injury markers, the extent of oxidative stress, inflammation, and the principal proteins involved in the Nrf-2/HO-1/NF-κB pathway. Additionally, network pharmacology techniques were utilized to discern potential SGD targets and their associated pathways. Administering SGD had a notable effect in counteracting the elevation of liver injury markers and pathological alterations induced by ATB-DILI. Moreover, there was a marked reduction in oxidative stress and inflammation in the treated rats. We identified 12 active compounds in SGD, with 88 shared targets between SGD and ATB-DILI. Subsequent KEGG analysis brought attention to pathways like MAPK, NF-κB, and IL-17 signaling. Our findings pave the way for more in-depth studies into the application of SGD in treating drug-induced liver injuries.

Naproxen-induced liver injury in a case of adult-onset Still's disease.

We present the case of a young female with fever, rash, and joint pain without any other history of connective tissue disorder, who was found on evaluation to have neutrophilic leucocytosis, elevated inflammatory markers and lymphadenopathy with hepatosplenomegaly. After extensive workup, the possibility of adult onset Still's disease was suggested by Yamaguchi criteria. She was started on naproxen, but later on developed drug-induced liver injury. She already had central serous retinopathy due to steroid use, and it was difficult to treat the adult-onset Stills disease due to the liver injury in view of contraindication to use of anti-inflammatory drugs but her illness was monocyclic and did not require further immunosuppression.

New finding based on Comparative Toxicogenomics Database: Hepatic YY1 mediates drug-induced liver injury

BackgroundYY1 plays a crucial part in the onset and progression of numerous liver diseases, yet the significant contribution of YY1 to drug-induced liver injury (DILI) appears to have been underestimated by researchers. PurposeTo reveal the underlying role of YY1 in DILI. MethodThe compounds that interact with YY1 were queried in the Comparative Toxicogenomics Database (CTD), with the majority found to be hepatotoxic, which includes certain widely used drugs. Molecular docking and SPR characterized the robust binding of hepatotoxic compounds to YY1. The duty of YY1 in DILI was investigated in Diosbulbin B (DIOB), a recently identified hepatotoxic compound that tightly associates with YY1, and further validated on ANIT, LCA, APAP, and CDDP. Transcriptomic analysis disclosed the underlying mechanisms involved in DIOB-induced liver injury. RT-qPCR, immunohistochemistry, immunofluorescence, western blotting, and cellular transfection techniques were employed to validate the specific mechanism. ResultsAmong the 94 compounds affecting YY1 expression in the CTD, 59 compounds exhibited hepatotoxicity, showing close interactions with YY1 and almost consistent binding sites by molecular docking. The SPR validated the tough binding of several hepatotoxic compounds to YY1, including five FDA-approved hepatotoxic drugs. Mechanistically, the involvement of YY1 in DILI was uncovered through the cholestasis lens, mice hepatic YY1 was up-regulated by hepatotoxic DIOB and transcriptionally inhibited FXR and its downstream BSEP and MRP2 expression, initiating early in cholestatic liver injury and persisting to drive the progression of cholestasis. ANIT and LCA-induced model of cholestasis provided evidence for the hypothesis that YY1 frequently mediates drug induced cholestasis (DIC). APAP and CDDP indicated that YY1 may also be involved in hepatocellular and mixed type DILI. ConclusionYY1 widely mediated the development of DIC and also might be engaged in other types of DILI. YY1 presented a common target for hepatotoxic medications and the targeting of liver YY1 for drug development may offer a novel approach for managing DILI.

Expanding the spectrum of progressive familial intrahepatic cholestasis: A report of 3 cases.

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders caused by defects in bile secretion or transport usually presenting as cholestasis in pediatric age. Herewith, we describe 3 PFIC cases with diagnostic challenges and highlight the role of genetic analysis. The clinical history, laboratory data, liver biopsy, and molecular analysis for each case were reviewed. Case 1, a Hispanic male from Puerto Rico with hepatomegaly since age 2 months, was eventually diagnosed with PFIC3 following identification of a homozygous splice site variant in ATP binding cassette subfamily B member 4 (ABCB4) (c.2784-12T>C) at age 17 years by whole-exome sequencing (WES). Case 2 was a 37-year-old man with a history of alcoholism, abnormal liver function tests, and ductopenia on biopsy. Molecular testing revealed a pathogenic heterozygous ABCB4 mutation (c.1633C>T) variant leading to a diagnosis of PFIC3. Case 3 was a 2-year-old female initially presenting as a drug-induced liver injury but was diagnosed with PFIC10 following identification of a heterozygous frameshift mutation (p.Asp300Trpfs*19) and a heterozygous missense mutation (c.1357T>C) in myosin VB (MYO5B) by WES. These PFIC cases highlight the heterogenous presentation and diagnostic challenges, and they emphasize the role of next-generation sequencing, particularly the utility of WES.

Idiosyncratic Hepatocellular Drug-Induced Liver Injury by Flucloxacillin with Evidence Based on Roussel Uclaf Causality Assessment Method and HLA B*57:01 Genotype: From Metabolic CYP 3A4/3A7 to Immune Mechanisms.

Idiosyncratic drug-induced liver injury (iDILI) by flucloxacillin presents as both cholestatic and hepatocellular injury. Its mechanistic steps are explored in the present analysis as limited data exist on the cascade of events leading to iDILI in patients with an established diagnosis assessed for causality by the Roussel Uclaf Causality Assessment Method (RUCAM). Studies with human liver microsomes showed that flucloxacillin is a substrate of cytochrome P450 (CYP) with ist preferred isoforms CYP 3A4/3A7 that toxified flucloxacillin toward 5'-hydroxymethylflucloxacillin, which was cytotoxic to human biliary epithelial cell cultures, simulating human cholestatic injury. This provided evidence for a restricted role of the metabolic CYP-dependent hypothesis. In contrast, 5'-hydroxymethylflucloxacillin generated metabolically via CYP 3A4/3A7 was not cytotoxic to human hepatocytes due to missing genetic host features and a lack of non-parenchymal cells, including immune cells, which commonly surround the hepatocytes in the intact liver in abundance. This indicated a mechanistic gap regarding the clinical hepatocellular iDILI, now closed by additional studies and clinical evidence based on HLA B*57:01-positive patients with iDILI by flucloxacillin and a verified diagnosis by the RUCAM. Naïve T-cells from volunteers expressing HLA B*57:01 activated by flucloxacillin when the drug antigen was presented by dendritic cells provided the immunological basis for hepatocellular iDILI caused by flucloxacillin. HLA B*57:01-restricted activation of drug-specific T-cells caused covalent binding of flucloxacillin to albumin acting as a hapten. Following drug stimulation, T-cell clones expressing CCR4 and CCR9 migrated toward CCL17 and CCL25 and secreted interferon-γ and cytokines. In conclusion, cholestatic injury can be explained metabolically, while hepatocellular injury requires both metabolic and immune activation.

A novel carboxylesterase 2-targeted fluorescent probe with cholic acid as a recognition group for early diagnosis of drug- and environment-related liver diseases

Due to the detrimental effects of various harmful substances—such as carcinogens, drug toxicity, and environmental pollutants—on the liver, which can trigger or exacerbate conditions like hepatocellular carcinoma (HCC), drug-induced liver injury (DILI), and non-alcoholic fatty liver disease (NAFLD), accurate detection and monitoring of these diseases are crucial for effective treatment. Carboxylesterase 2 (CES2) is primarily found in the liver and, as a potential biomarker, its accurate detection can enhance the early diagnosis and treatment efficacy of liver diseases. Traditional fluorescence probes for CES2 detection suffer from non-specific recognition groups, leading to poor targeting specificity. To address this limitation, we propose a novel CES2-responsive fluorescent probe utilizing cholic acid (CA) as a recognition group. The probe, LAN-CA, was synthesized by esterifying CA with a near-infrared fluorophore, LAN-OH. This novel fluorescent probe leverages the unique affinity of CA for hepatocytes, ensuring that LAN-CA remains and accumulates specifically within the hepatoenteric circulation. In vitro experiments showed that the probe exhibits superior optical performance compared to traditional benzoate-based probe (LAN-PH), with a detection limit of 0.015 μg/mL. Examination of 56 common biological interferents demonstrated that using CA as a recognition group offers high selectivity. Cell experiments confirmed that LAN-CA is an effective tool for monitoring endogenous CES2 in live cells. Comprehensive evaluations of fluorescence imaging in various mouse models of liver diseases, such as HCC, DILI, and NAFLD, demonstrated that LAN-CA provides exceptional imaging accuracy and therapeutic monitoring capabilities. In conclusion, this probe not only can be a promising tool for accurate liver disease diagnosis, but also can provide valuable insights into treatment efficacy.

Viral etiologies of acute liver failure.

Acute liver failure (ALF) is a rare cause of liver-related mortality worldwide, with an estimated annual global incidence of more than one million cases. While drug-induced liver injury, including acetaminophen toxicity, is the leading cause of ALF in the Western world, viral infections remain a significant cause of ALF and the most common cause in many developing nations. Given the high mortality rates associated with ALF, healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis, rapid treatment initiation when possible, and optimal management, which may include liver transplantation. This review aims to provide a summary of viral causes of ALF, diagnostic approaches, treatment options, and expected outcomes.

Propensity score matching-based analysis of the effect of corticosteroids in treating severe drug-induced liver injury

Background and aimThere is no conventional treatment for patients with severe drug-induced liver injury (DILI) except for discontinuation of liver injury drugs and symptomatic supportive therapy. Opinions on whether corticosteroids can be used to treat severe DILI are conflicting, and most of the relevant clinical studies are case reports or retrospective studies, which still need to be supported by high-level evidence-based medical studies. This study aimed to evaluate the effect and tolerance of corticosteroids in patients with severe DILI. Risk factors associated with patient failure to cure were also explored. MethodsPropensity score matching based on nearest-neighbor 1:1 matching was used to screen severe DILI patients in the corticosteroids and control groups. Severe DILI was defined as elevated serum ALT and/or ALP with TBIL≥5 ULN (5 mg/dL or 85.5 μmol/L) with or without INR ≥1.5. Patients were treated with conventional therapy combined with corticosteroids in the corticosteroids group and only conventional therapy in the control group. ResultsA total of 146 patients, 73 each in the corticosteroids and control groups, were included in this study. By analyzing the entire cohort, we found no significant difference in cure rates between patients in the corticosteroid group and control group (34.2% vs. 20.5 %, p = 0.095), and there was no significant difference in the incidence of adverse effects between the two groups (20.5% vs. 20.5 %, p = 1.000). However, TBIL decreased more in the corticosteroids group on day 7 (89.2 ± 107.6 μmol/L vs. 58.8 ± 70.7 μmol/L, p = 0.046). In subgroup analyses, patients whose TBIL remained elevated despite conventional treatment had a higher TBIL decline on day 7,14 after use of corticosteroid (99.2 ± 98.5μmol/L vs. -23.3 ± 50.4μmol/L, p < 0.001; 120 ± 119.1μmol/L vs. 61.2 ± 98.5μmol/L, p = 0.047). The cure rate of patients in the corticosteroid group was significantly higher than that of the control group (36.1 % versus 4.5 %, p = 0.016). The proportion of patients with TBIL <85.5 μmol/L was also significantly higher in the corticosteroid group than in the control group at day 7 (p = 0.016) and day 14 (p = 0.004) after treatment. In the subgroup analysis of patients with different clinical phenotypes, the causative agent was herbal, autoimmune antibody-positive and 40 % < PTA ≤ 50 % of patients, corticosteroid use did not increase the cure rate of the patients. Univariate and multifactorial analyses found corticosteroid use to be a protective factor for failure to cure in patients with severe DILI (p < 0.001, OR:0.191,95 % CI:0.072–0.470), and peak TBIL to be a risk factor (p = 0.003, OR:1.016,95 % CI:1.007–1.028). ConclusionsThe addition of corticosteroids could not increase the cure rate in patients with severe DILI, but it could rapidly reduce the patient's TBIL at an earlier stage. Corticosteroids could also promote curing in patients with elevated TBIL after conventional treatment. Corticosteroid use was a protective factor for failure to cure in patients with severe DILI and peak TBIL was a risk factor.

Incidence of Idiosyncratic Drug-Induced Liver Injury Caused by Prescription Drugs.

The incidence of drug-induced liver injury (DILI) is not known for most prescription medications. We aimed to estimate the incidence of DILI for commonly prescribed outpatient drugs. To establish a baseline estimate of DILI incidence, we used the estimated incidence (EI) of amoxicillin/clavulanate DILI from a previous population-based study in Iceland. This was combined with the multicenter prospective DILI Network (DILIN) cohort and the US population-based Medical Expenditure Panel Survey (MEPS). From 2005 to 2019, prescription drugs with at least five bona fide DILIN cases and data from at least 10 of the 15years from MEPS during that timeframe were included. The EI for 'drug A' was calculated as follows: RESULTS: In total, 30 drugs met the inclusion criteria, of which 11 were antibiotics, 4 were antiepileptic drugs (AEDs), 4 were statins, and 11 were other drug types. The highest EI was seen with azathioprine and older AEDs, with one DILI case per 349-2329 new prescriptions. The EI of antibiotics ranged greatly, with the highest risk seen for minocycline, amoxicillin/clavulanate, and nitrofurantoin (approximately 1:1000-2400 new prescriptions), and lowest risk for clindamycin, doxycycline, azithromycin, and amoxicillin (approximately 1:40,000-170,000 new prescriptions). The EI for commonly prescribed statins was approximately 1:10,000-50,000. Important medication classes with > 5 million new prescriptions from 2005 to 2019 but fewer than five DILIN cases included β-blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and metformin, which presumably have very low DILI incidence. The highest EI was found for azathioprine, older antiepileptics, and minocycline. In contrast, many widely used drugs are rare causes of DILI. These findings may help clinicians better weigh potential benefits of medications against hepatotoxicity risk.

Retrospective evaluation of medical information for predicting tazobactam/piperacillin-induced liver injury.

Tazobactam/piperacillin is a first-line treatment option for hospital-acquired pneumonia; however, drug-induced liver injury (DILI) is relatively frequently observed with tazobactam/piperacillin in clinical practice. This study aimed to verify the usefulness of available patient data for predicting DILI prior to tazobactam/piperacillin administration. Tazobactam/piperacillin-treated patients were retrospectively selected and divided into patients with and without DILI. Comparative analysis was performed regarding age, gender, dose, duration of treatment, clinical laboratory values prior to treatment initiation, and the types of organ-specific infections in both groups. Multiple logistic regression analyses indicated that elevated C-reactive protein (odds ratio (OR), 1.284; 95% confidence interval (CI), 1.172 - 1.406; p < 0.001) and high hemoglobin (OR, 1.697; 95% CI, 1.259 - 2.286; p < 0.001) levels prior to the administration of tazobactam/piperacillin were risk factors for DILI in males who received a 4.5-g dose. A predictive model for DILI risk was constructed by combining these test values and analyzed using receiver operating characteristic curves, obtaining 0.910 for the model construction set and 0.845 for the validation set. The development of DILI was predicted with good accuracy in males who received a 4.5-g dose with elevated C-reactive protein and hemoglobin.

Time to use the right classification to predict the severity of checkpoint inhibitor-induced liver injury, as assessed for causality using the updated RUCAM.

While immune checkpoint inhibitors (ICIs) are revolutionising cancer therapy, checkpoint inhibitor-induced liver injury is a significant immune-related side effect of this immunotherapy. This study focuses on the severity classifications and characteristics of patients with checkpoint inhibitor-induced hepatitis. A retrospective analysis of patients with severe Checkpoint Inhibitor-induced hepatitis grade 3 and 4 according to the recommended Common Terminology Criteria for Adverse Events (CTCAE) classification was conducted. Data on clinicobiological characteristics, treatment and outcomes were collected from 3 university hospitals, and causality was assessed by using the updated Roussel Uclaf Causality Assessment Method. The severity of hepatitis was assessed using the Model for End-stage Liver Disease score, the Drug-Induced Liver Injury Network, and the Drug-Induced Liver Injury International Expert Working Group classifications. We retrospectively included 100 patients presenting various hepatitis patterns with a median time to onset of 20 days after checkpoint inhibitors. Severity grading varied significantly among the classifications used. A lower incidence of severe cases was observed when using the Drug-Induced Liver Injury classifications instead of the recommended CCTCAE classification, and this was correlated with outcomes. This retrospective study challenges the efficacy of the CTCAE classification in defining the severity of Checkpoint Inhibitor-induced hepatitis and suggests that the traditional hepatology-focused scores may be more relevant. The CTCAE classification is inconsistent and gives equal weight to jaundice and elevated transaminases, which leads to steroid overtreatment and limits the rechallenge of ICIs.

Triptolide-induced acute liver injury and its mechanism with estradiol in regulating macrophage-mediated inflammation and hepatocyte function

Triptolide (TP), a diterpene from Tripterygium wilfordii, exhibits potent anti-inflammatory, immunomodulatory, and antitumor properties but is limited by severe hepatotoxicity. This study investigates sex differences in TP-induced liver injury and the protective role of estradiol (E2) in modulating macrophage-mediated inflammation and hepatocyte function. An acute liver injury model was established in male and female Balb/c mice using intraperitoneal TP injection. Liver function tests, histological analyses, and immunohistochemical staining were performed. THP-1 macrophage and various liver cell lines were used to study the effects of TP and E2 in vitro. Virtual screening, molecular docking, luciferase assays, and qPCR were employed to identify potential targets and elucidate underlying mechanisms. TP caused more severe liver injury in female mice, evidenced by increased liver indices, aspartate aminotransferase (AST) levels, and extensive hepatocyte damage. TP promoted M1 macrophage polarization, enhancing inflammation, particularly in female mice. E2 mitigated TP-induced inflammatory responses by downregulating pro-inflammatory cytokines and macrophage activation markers. Molecular docking and functional assays identified Nuclear receptor subfamily 1 group I member 2 (NR1I2) as a key target mediating the protective effects of E2. The study highlights significant sex differences in TP-induced hepatotoxicity, with females being more susceptible. E2 exerts protective effects against TP-induced liver injury by modulating immune responses, presenting a potential therapeutic approach to mitigate drug-induced liver injury (DILI). Further research on NR1I2 could lead to targeted therapies for reducing drug-induced liver damage.

Development of a Modular miRNA-Responsive Biosensor for Organ-Specific Evaluation of Liver Injury.

MicroRNAs (miRNAs) are increasingly being considered essential diagnostic biomarkers and therapeutic targets for multiple diseases. In recent years, researchers have emphasized the need to develop probes that can harness extracellular miRNAs as input signals for disease diagnostics. In this study, we introduce a novel miRNA-responsive biosensor (miR-RBS) designed to achieve highly sensitive and specific detection of miRNAs, with a particular focus on targeted organ-specific visualization. The miR-RBS employs a Y-structured triple-stranded DNA probe (Y-TSDP) that exhibits a fluorescence-quenched state under normal physiological conditions. The probe switches to an activated state with fluorescence signals in the presence of high miRNA concentrations, enabling rapid and accurate disease reporting. Moreover, the miR-RBS probe had a modular design, with a fluorescence-labeled strand equipped with a functional module that facilitates specific binding to organs that express high levels of the target receptors. This allowed the customization of miRNA detection and cell targeting using aptameric anchors. In a drug-induced liver injury model, the results demonstrate that the miR-RBS probe effectively visualized miR-122 levels, suggesting it has good potential for disease diagnosis and organ-specific imaging. Together, this innovative biosensor provides a versatile tool for the early detection and monitoring of diseases through miRNA-based biomarkers.

Herbal extracts in hepatoprotection: antioxidant and immunomodulatory effects. A review

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

Shenqi Pill alleviates acetaminophen-induced liver injury: a comprehensive strategy of network pharmacology and spectrum-effect relationship reveals mechanisms and active components

BackgroundAcetaminophen (APAP), commonly used for its antipyretic and analgesic properties, can cause severe liver injury or even acute liver failure when overdosed. However, the options for treating APAP-induced liver toxicity are limited. Shenqi Pill (SQP), a traditional Chinese herbal formula, has shown effectiveness in treating various liver ailments. SQP consists of cinnamon, aconite, rehmannia, cornus, peony bark, Chinese yam, poria, and alisma in a ratio of 1:1:8:4:3:4:3:3. However, the mechanisms and active components of SQP that counteract drug-induced liver injury (DILI) are not well understood. PurposeThis study aimed to explore the protective effects of SQP against APAP-induced liver injury in both laboratory and animal settings. It seeks to identify the active components and potential mechanisms by which SQP targets mitochondria to alleviate liver damage. MethodsA mouse model with APAP-induced liver injury was established to assess SQP's therapeutic impact. This study then analyzed the components of SQP using UPLC-Q-TOF-MS in both in vivo and in vitro environments. Network pharmacology and the GEO database helped predict potential pathways and targets. Potential active components were identified through spectrum-effect relationship analysis and validated their efficacy using Seahorse assays and molecular docking. ResultsTreatment with SQP significantly reduced liver dysfunction, tissue damage, lipid metabolic disruptions, and inflammation caused by APAP in mice. In cellular tests, SQP-treated serum notably enhanced mitochondrial function, maintained membrane potential, decreased ROS levels, and prevented mitochondrial permeability transition pore opening. Biochemically, SQP reversed the suppression of p-AMPK, p-ACC, CPT1, and ACADM expression caused by APAP overdose. This study identified 97 in vitro and 24 in vivo components of SQP, with eight showing significant mitochondrial benefits. Molecular docking studies suggest that fuziline and paeoniflorin could activate AMPK. ConclusionSQP effectively mitigates APAP-induced liver injury by enhancing mitochondrial function via the AMPK-ACC-CPT1-ACADM pathway. Moreover, this study introduces a novel strategy for analyzing the relationship between the chemical and pharmacological properties of drug-containing serum, successfully identifying compounds with mitochondrial activity. Fuziline and paeoniflorin, in particular, emerge as promising mitochondrial protectants and warrant further investigation. This research underpins the development of innovative treatments for DILI using SQP and its components.