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Chemiluminescence (CL) with the elimination of excitation light and minimal autofluorescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H₂S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD-950)] by covalently connecting two Schaap’s dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (~60 min), deeper tissue penetration (~10 mm), and specific H₂S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5-fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.

Introduction: Methotrexate is often used as the first line of systemic treatment in patients with moderate to severe psoriasis and psoriatic arthritis.Case report: We present the case of a 44-year-old male patient with moderate plaque psoriasis who was treated with Methotrexate and diagnosed with mild hepatic steatosis during the first month of treatment. Using FIB-4 (Fibrosis Index Based on 4 factors) as a noninvasive method for assessing the risk of liver fibrosis, the patient was able to take Methotrexate safely, with close monitoring of liver function.Conclusions: FIB-4 can be used to assess the risk of liver fibrosis in psoriasis patients treated with Methotrexate to ensure better adherence to the treatment.

Abstract This is a case control and cohort study, conducted at Department of Biochemistry in FUAST, compressing 24 number of albino Wistar rats. Illicium verum (star anise) natural spice and green vegetable broccoli are used for chemo-preventive herbal treatment in relation with vitamin C antioxidant activity. Hepatotoxicity was induced in liver of model rats by giving interperitoneally single injection of 200 mg/kg bod weight (B.W) of N-nitrosodiethylamine and orally giving 1 mg/kg BW phenobarbital for 14 days during disease prorogation period. The vitamin C analysis from Illicium verum (star anise), green broccoli, orange juice, orange peel and orange pulp was done by iodometric quantitative and qualitative titration method. Rats were given compound according to their bodyweight as 1 mg/kg B.W. After 14 days (Disease Promotion and Propagation Period) and 28 days (Disease cure period) of treatment behavioral activity was monitored by locomotors activity in open field experiment, stimulatory activity in home cage and anxiolytic effects observed in light and dark apparatus and also in T maze. Behavioral activity were significantly increased in Illicium verum and green broccoli treated rats. Hematological study including hemoglobin (Hb), white blood cells (WBC), red blood cells (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW) and Platelets was done by abbot laboratory analyzer cell. The value of Hb and RBC was also significantly increased in star anise and broccoli treated rats, showed proper function of RBC in microcirculation. WBC was also in normal range revealed that no disease regards to bone marrow and leukemia’s. The biochemical activity of rats including urea, creatinine, total protein, albumin, globulin, A/G ratio, amylase and calcium in blood serum were analyzed while, liver health or performance was also determined by LFT (liver function test). Behavioral and laboratorial variables were analyzed by using SPSS v. 20 and p-value < 0.05 was considered statistically significant. The study report noticeable significant effect of Illicium verum and broccoli on hepatotoxicity of experimental model. Recent experimental study statistical outcomes show reciprocal relationship between the consumption of vegetable diet and natural spice with the risk of Hepatotoxicity. Thus, the aim of the study is to enhance the function of star anise or illicium verum natural spice and green vegetable broccoli as an anticancer or chemoprophylaxis agent. Resumo Trata-se de um estudo de caso controle e coorte, realizado no Departamento de Bioquímica da FUAST, comprimindo 24 ratos albinos Wistar. A especiaria natural Illicium verum (anis estrelado) e o brócolis vegetal verde geralmente são utilizados para o tratamento fitoterápico quimiopreventivo por conta da atividade antioxidante da vitamina C. A hepatotoxicidade foi induzida no fígado dos ratos modelo por injeção única interperitoneal de 200 mg/kg de peso corporal (PC) de N-nitrosodietilamina e administração oral de 1 mg/kg de peso corporal de fenobarbital por 14 dias durante o período de prolongamento da doença. A análise da vitamina C de Illicium verum (anis estrelado), brócolis verde, suco de laranja, casca de laranja e polpa de laranja foi realizada pelo método de titulação quantitativa e qualitativa iodométrica. Os ratos receberam composto de acordo com seu peso corporal como 1 mg/kg B.W. Após 14 dias (Período de Promoção e Propagação da Doença) e 28 dias (Período de Cura da Doença) de tratamento a atividade comportamental foi monitorada por atividade locomotora em experimento de campo aberto, atividade estimulatória em gaiola e efeitos ansiolíticos observados em aparelhos claros e escuros e também em T Labirinto. A atividade comportamental foi significativamente aumentada em ratos tratados com Illicium verum e brócolis verde. O estudo hematológico incluindo hemoglobina (Hb), glóbulos brancos (WBC), glóbulos vermelhos (RBC), volume corpuscular médio (MCV), hemoglobina corpuscular média (MCH), concentração média de hemoglobina corpuscular (MCHC), largura de distribuição de glóbulos vermelhos (RDW) e Plaquetas foi feito pela célula do analisador de laboratório Ababot. O valor de Hb e RBC também foi significativamente aumentado em ratos tratados com anis estrelado e brócolis, mostraram função adequada de RBC na microcirculação. WBC também estava na faixa normal revelando que nenhuma doença relaciona-se à medula óssea e leucemia. A atividade bioquímica de ratos, incluindo uréia, creatinina, proteína total, albumina, globulina, razão A/G, amilase e cálcio no soro sanguíneo foram analisadas, enquanto a saúde ou desempenho do fígado também foi determinada por LFT (teste de função hepática). As variáveis comportamentais e laboratoriais foram analisadas pelo SPSS v. 20 e valor de p < 0,05 foi considerado estatisticamente significativo. O estudo relata efeito significativo perceptível de Illicium verum e brócolis na hepatotoxicidade do modelo experimental. Resultados estatísticos de estudos experimentais recentes mostram relação recíproca entre o consumo de dieta vegetal e tempero natural com o risco de hepatotoxicidade. Assim, o objetivo do estudo foi potencializar a função do anis estrelado ou da especiaria natural Illicium verum e do brócolis vegetal verde como agente anticancerígeno ou quimioprofilático.

Toxicity studies, among them hepatotoxicity, are key throughout preclinical stages of drug development to minimise undesired toxic effects that might eventually appear in the course of the clinical use of the new drug. Understanding the mechanism of injury of hepatotoxins is essential to efficiently anticipate their potential risk of toxicity in humans. The use of in vitro models and particularly cultured hepatocytes represents an easy and robust alternative to animal drug hepatotoxicity testing for predicting human risk. Here, we envisage an innovative strategy to identify potential hepatotoxic drugs, quantify the magnitude of the alterations caused, and uncover the mechanisms of toxicity. This strategy is based on the comparative analysis of metabolome changes induced by hepatotoxic and non-hepatotoxic compounds on HepG2 cells, assessed by untargeted mass spectrometry. As a training set, we used 25 hepatotoxic and 4 non-hepatotoxic compounds and incubated HepG2 cells for 24 h at a low and a high concentration (IC10 and IC50) to identify mechanism-related and cytotoxicity related metabolomic biomarkers and to elaborate prediction models accounting for global hepatotoxicity and mechanisms-related toxicity. Thereafter, a second set of 69 chemicals with known predominant mechanisms of toxicity and 18 non-hepatotoxic compounds were analysed at 1, 10, 100 and 1000 µM concentrations from which and based on the magnitude of the alterations caused as compared with non-toxic compounds, we defined a “toxicity index” for each compound. In addition, we extracted from the metabolome data the characteristic signatures for each mechanism of hepatotoxicity. The integration of all this information allowed us to identify specific metabolic patterns and, based on the occurrence of that specific metabolome changes, the models predicted the likeliness of a compound to behave as hepatotoxic and to act through a given toxicity mechanism (i.e., oxidative stress, mitochondrial disruption, apoptosis and steatosis) for each compound and concentration.

Drug hepatotoxicity assessment is a relevant issue both in the course of drug development as well as in the post marketing phase. The use of human relevant in vitro models in combination with powerful analytical methods (metabolomic analysis) is a promising approach to anticipate, as well as to understand and investigate the effects and mechanisms of drug hepatotoxicity in man. The metabolic profile analysis of biological liver models treated with hepatotoxins, as compared to that of those treated with non-hepatotoxic compounds, provides useful information for identifying disturbed cellular metabolic reactions, pathways, and networks. This can later be used to anticipate, as well to assess, the potential hepatotoxicity of new compounds. However, the applicability of the metabolomic analysis to assess the hepatotoxicity of drugs is complex and requires careful and systematic work, precise controls, wise data preprocessing and appropriate biological interpretation to make meaningful interpretations and/or predictions of drug hepatotoxicity. This review provides an updated look at recent in vitro studies which used principally mass spectrometry-based metabolomics to evaluate the hepatotoxicity of drugs. It also analyzes the principal drawbacks that still limit its general applicability in safety assessment screenings. We discuss the analytical workflow, essential factors that need to be considered and suggestions to overcome these drawbacks, as well as recent advancements made in this rapidly growing field of research.