Chemico-Biological Interactions最新文献

Neurotoxicity and mechanism of metal and metal oxide nanoparticles 金属和金属氧化物纳米颗粒的神经毒性及其机制

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-02-03 DOI: 10.1016/j.cbi.2026.111953

Shouying Cao , Meng Tang , Changcun Bai

Metal and metal oxide nanoparticles, owing to their unique physicochemical properties, have been extensively applied in biomedicine, cell labeling and sorting, drug delivery, and clinical therapy. Their impact on human health and environmental safety is increasingly drawing attention. These nanoparticles can enter the nervous system through multiple pathways, triggering the release of reactive oxygen species and cytokines, leading to blood-brain barrier damage and central nervous system dysfunction. This paper includes a methods section detailing literature search strategies, screening criteria, and time windows. It explores pathways for metal and metal oxide nanoparticles to enter the nervous system and their neurotoxic effects in vivo and in vitro. The influence of developmental stage and gender differences on the neurotoxicity of metal and metal oxide nanoparticles is clearly articulated. It systematically reviews and critically compares key molecular and cellular mechanisms underlying neurotoxicity induced by different types of metal and metal oxide nanoparticles, revealing their intrinsic connections and cascading effects. It critically evaluates particle effects versus ionic effects and grades the strength of particle-specific toxicity evidence. Factors influencing the toxicity of metal and metal oxide nanoparticles, including particle size, exposure concentration, and solubility are discussed. The neurotoxic characteristics and potential unique mechanisms distinguishing these nanoparticles from other nanomaterials are clarified. Possible mechanisms of neurotoxicity and physicochemical factors influencing toxicity are summarized, exploring how physicochemical properties determine interactions with the nervous system and toxicity severity. This review concludes by identifying existing challenges and future research directions regarding the neurotoxic effects of metal and metal oxide nanoparticles, providing a reference framework for their safety assessment and neurotoxicity studies.

金属和金属氧化物纳米颗粒由于其独特的物理化学性质，在生物医学、细胞标记和分选、药物传递和临床治疗等方面得到了广泛的应用。它们对人类健康和环境安全的影响日益引起人们的关注。这些纳米颗粒可以通过多种途径进入神经系统，触发活性氧和细胞因子的释放，导致血脑屏障损伤和中枢神经系统功能障碍。本文包括方法部分，详细介绍文献检索策略、筛选标准和时间窗口。它探讨了金属和金属氧化物纳米颗粒进入神经系统的途径及其在体内和体外的神经毒性作用。发育阶段和性别差异对金属和金属氧化物纳米颗粒神经毒性的影响是明确的。它系统地回顾和批判性地比较了不同类型的金属和金属氧化物纳米颗粒诱导神经毒性的关键分子和细胞机制，揭示了它们的内在联系和级联效应。它批判性地评估粒子效应与离子效应，并对粒子特异性毒性证据的强度进行分级。讨论了影响金属和金属氧化物纳米颗粒毒性的因素，包括粒径、暴露浓度和溶解度。阐明了这些纳米颗粒的神经毒性特征和区别于其他纳米颗粒的潜在独特机制。综述了神经毒性的可能机制和影响毒性的物理化学因素，探讨了物理化学特性如何决定与神经系统的相互作用和毒性严重程度。本文总结了金属和金属氧化物纳米颗粒在神经毒性方面存在的挑战和未来的研究方向，为其安全性评估和神经毒性研究提供了参考框架。

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引用次数: 0

ALKBH5-mediated autophagic flux impairment is involved in bilirubin neurotoxicity alkbh5介导的自噬通量损伤与胆红素神经毒性有关

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-28 DOI: 10.1016/j.cbi.2026.111940

Jinfu Zhou , Sining Liao , Chenran Zhang , Guilin Li , Fuli Zheng , Guangxia Yu , Hong Hu , Wenya Shao , Zhenkun Guo , Siying Wu , Jianping Tang , Huangyuan Li

Bilirubin-induced brain damage represents a serious clinical consequence of hyperbilirubinemia, yet the role and underlying molecular mechanisms of autophagy the remain largely elusive. Here, we demonstrate that, for the first time, N6-methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) mediated dysregulated autophagic flux contributes to bilirubin-induced neurotoxicity. Hyperdifferential differentiated PC12 cells and neonatal Sprague-Dawley rats were employed as in vitro and in vivo models, respectively. In vivo experiments first showed a dysregulated autophagy and neuronal damage in hyperbilirubinemia. In vitro further experiments observed that bilirubin exposure inhibited autophagy as illustrated by the downregulated p62 and LC3-II protein expression and transmission electron microscopy results. Furthermore, we found that the autophagic flux impairment was due to the inhibition of initial stage following bilirubin exposure, which was pharmacologically validated using rapamycin and bafilomycin A1 and up-regulated protein expression of p-mTOR and BCL2. More importantly, we found that ALKBH5 overexpression can exacerbate bilirubin-induced autophagic flux damage, whereas ALKBH5 knockdown attenuated the inhibited autophagic flux damage. Mechanistically, Vacuole membrane protein 1 (VMP1), Ras-related GTP-binding protein C (RRAGC), and protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1) were identified as the target genes of ALKBH5 to impair autophagic flux with mRNA stability assay, RT-PCR analysis, and bioinfomatic analysis, thereby promoting bilirubin-induced neurotoxicity. Collectively, our findings reveal that ALKBH5 participates in bilirubin-induced autophagic flux impairment, and propose m6A-dependent autophagy as a potential therapeutic target in hyperbilirubinemia.

胆红素诱导的脑损伤是高胆红素血症的严重临床后果，然而自噬的作用和潜在的分子机制在很大程度上仍然是难以捉摸的。在这里，我们首次证明n6 -甲基腺苷（m6A）去甲基化酶AlkB同源物5 （ALKBH5）介导的失调自噬通量有助于胆红素诱导的神经毒性。采用高分化PC12细胞和新生大鼠Sprague-Dawley分别作为体外和体内模型。体内实验首次显示了高胆红素血症的自噬失调和神经元损伤。进一步的体外实验观察到胆红素暴露抑制自噬，p62和LC3-II蛋白表达下调和透射电镜结果表明。此外，我们发现自噬通量损伤是由于胆红素暴露后初始阶段的抑制，使用雷帕霉素和巴菲霉素A1以及上调p-mTOR和BCL2蛋白表达证实了这一点。更重要的是，我们发现ALKBH5过表达可加重胆红素诱导的自噬通量损伤，而ALKBH5敲低可减轻受抑制的自噬通量损伤。机制上，通过mRNA稳定性分析、RT-PCR分析和生物信息学分析，确定液泡膜蛋白1 （VMP1）、ras相关gtp结合蛋白C （RRAGC）和蛋白激酶amp活化的催化亚单位α 1 （PRKAA1）是ALKBH5损害自噬通量的靶基因，从而促进胆红素诱导的神经毒性。总之，我们的研究结果表明ALKBH5参与了胆红素诱导的自噬通量损伤，并提出m6a依赖性自噬是高胆红素血症的潜在治疗靶点。

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引用次数: 0

Recurrent amoxicillin exposure disrupts colonic homeostasis through oxidative stress, DNA repair dysregulation, and gut dysbiosis-driven inflammation 反复的阿莫西林暴露会通过氧化应激、DNA修复失调和肠道生态失调引起的炎症破坏结肠内稳态

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-26 DOI: 10.1016/j.cbi.2026.111939

Nabila Akhtara, Manuj Kr Bharali

The present study investigated the impact of recurrent amoxicillin exposure on colonic health in a mouse model, applying a multi-parametric approach. Twenty animals were randomly divided into two groups, out of which one group received oral amoxicillin (100 mg/kg BW), administered every other week for twelve weeks. Histological and ultra-structural analyses (SEM and TEM) of colonic tissues revealed crypt degeneration, mucosal thinning, and inflammatory cell infiltration in the treated group. Biochemical assays demonstrated significantly elevated lipid peroxidation along with reduced antioxidant defences, indicative of oxidative stress. Immunohistochemistry confirmed oxidative DNA damage, accompanied by aberrant expression of DNA repair genes, indicating impaired genomic maintenance. Faecal microbiota profiling showed a pronounced loss of microbial load and enrichment of opportunistic pathogens, alongside a paradoxical increase in short-chain fatty acid levels. These alterations correlated with significantly upregulated inflammatory gene expression (TNF-α, IFN-γ, IL-6, IL-17 & IL-1β), indicating microbiome destabilization and heightened inflammatory signalling. Overall, recurrent amoxicillin exposure disrupted colonic homeostasis through dysbiosis, oxidative stress, genotoxicity, and inflammation, underscoring the potential risks of antibiotic therapy.

本研究采用多参数方法研究了反复阿莫西林暴露对小鼠模型结肠健康的影响。将20只动物随机分为两组，其中一组给予阿莫西林（100 mg/kg BW）口服，每隔一周给药，连续12周。治疗组结肠组织的组织学和超微结构分析（SEM和TEM）显示隐窝变性，粘膜变薄，炎症细胞浸润。生化分析表明，脂质过氧化显著升高，抗氧化防御能力降低，表明氧化应激。免疫组织化学证实了氧化性DNA损伤，伴随着DNA修复基因的异常表达，表明基因组维护受损。粪便微生物群分析显示微生物负荷明显减少，机会性病原体富集，同时短链脂肪酸水平矛盾地增加。这些改变与炎症基因表达（TNF-α、IFN-γ、IL-6、IL-17和IL-1β）显著上调相关，表明微生物组不稳定和炎症信号传导增强。总的来说，复发性阿莫西林暴露通过生态失调、氧化应激、遗传毒性和炎症破坏结肠内稳态，强调了抗生素治疗的潜在风险。

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引用次数: 0

Sex-dependent effects of early-life paracetamol exposure on behavior and monoamines in the rat central nervous system 幼年扑热息痛暴露对大鼠中枢神经系统行为和单胺的性别依赖性影响。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-24 DOI: 10.1016/j.cbi.2026.111937

Filip Górawski, Ilona Joniec-Maciejak, Agnieszka Piechal, Justyna Pyrzanowska, Dagmara Mirowska-Guzel, Kamilla Blecharz-Klin

The effects of prenatal and early postnatal paracetamol exposure on behavior and neurotransmission in offspring remain poorly understood. The aim of this study was to investigate the consequences of paracetamol administration during fetal and early postnatal development period in rats. A total of 43 offspring prenatally exposed to paracetamol were assigned to experimental groups based on dose (10 or 30 mg/kg b.w.) and stratified by sex.

Paracetamol was administered throughout the entire prenatal period and during the first three months of postnatal life, with treatment continuing during the behavioral assessments. These included the Novel Object Recognition test, Staircase test, Hole Board, and Morris Water Maze, which were conducted to evaluate exploratory behavior, motor function, anxiety, and memory.

Neurochemical analyses of neurotransmitters level in forebrain regions (prefrontal cortex, hippocampus, hypothalamus, striatum), hindbrain regions (cerebellum, medulla oblongata), and spinal cord were performed using high-performance liquid chromatography (HPLC).

The behavioral response to paracetamol differed between sexes. Paracetamol exposure enhanced exploration and produced a moderate anxiolytic effect, which was more pronounced in females and increased dose-dependently. Furthermore, sex-dependent impairments in spatial memory recall were observed in the Water Maze test, particularly in females exposed to paracetamol.

Biochemically, paracetamol exposure led to significant changes in dopaminergic and noradrenergic systems between the sexes, particularly in the hypothalamus (e.g., increased noradrenaline and dopamine turnover and their metabolites in males) and medulla oblongata (e.g. decreased noradrenalin turnover in males) indicating a sex-specific neurochemical response. These findings suggest that paracetamol exposure during critical developmental periods may influence cognitive function and neurotransmitter regulation in a sex-dependent manner, with female and male offspring demonstrating different neurobehavioral outcomes.

产前和产后早期扑热息痛暴露对后代行为和神经传递的影响仍然知之甚少。本研究的目的是探讨对乙酰氨基酚在大鼠胎儿和出生后早期发育期间的影响。将43只产前接触扑热息痛的子代按剂量（10或30 mg/kg b.w）和性别分层分为实验组。扑热息痛在整个产前和出生后的头三个月都被使用，在行为评估期间继续治疗。这些测试包括新物体识别测试、楼梯测试、孔板测试和莫里斯水迷宫，用于评估探索行为、运动功能、焦虑和记忆。采用高效液相色谱法（HPLC）分析前脑区（前额皮质、海马、下丘脑、纹状体）、后脑区（小脑、延髓）和脊髓的神经递质水平。对扑热息痛的行为反应因性别而异。扑热息痛暴露增强探索并产生适度的抗焦虑作用，这在女性中更为明显，且剂量依赖性增强。此外，在水迷宫测试中观察到空间记忆回忆的性别依赖性损伤，特别是在暴露于扑热息痛的女性中。生物化学方面，扑热息痛暴露导致两性间多巴胺能和去甲肾上腺素能系统的显著变化，特别是下丘脑（例如，雄性去甲肾上腺素和多巴胺的代谢增加）和延髓（例如，雄性去甲肾上腺素的代谢减少）表明了一种性别特异性的神经化学反应。这些发现表明，在发育关键期暴露扑热息痛可能会以性别依赖的方式影响认知功能和神经递质调节，雌性和雄性后代表现出不同的神经行为结果。

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引用次数: 0

Cytochrome P450-mediated detoxification and NF-κB/NLRP3 pathway-driven hepatotoxicity of emodin: Multiomics and laboratory evidence 细胞色素p450介导的解毒和NF-κB/NLRP3通路驱动的大黄素肝毒性：多组学和实验室证据。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-22 DOI: 10.1016/j.cbi.2026.111934

Lili Wu , Siyu Chen , Qiyuan Yang , Xing Li , Lingyan Liu , Shengjun Ji , Shuaiyuan Tang , Sihui Zhang , Yan Wang , Runzhi Chen , Zhikun Zhan

Emodin, a bioactive compound abundant in Chinese medicinal herbs, possesses broad therapeutic potential but raises safety concerns due to conflicting reports of hepatotoxicity. This study investigated the toxicological mechanisms underlying emodin-induced liver injury. Emodin (25–100 μM) elicited dose-dependent cytotoxicity in HepG2 cells, with the cytochrome P450 (CYP) enzymes CYP1A2 and CYP3A4 identified as the primary enzymes metabolizing emodin into hydroxylated products (M1-M3). The comparative cytotoxicity assay of emodin and its metabolites in HepG2 cells indicated that CYP-mediated metabolism functions as a critical detoxification pathway. Moreover, inhibition of CYP with 1-aminobenzotriazole (ABT, 500 μM) markedly enhanced emodin (12.5–100 μM) cytotoxicity in HepG2 cells. Similarly, ABT (50 mg/kg) markedly exacerbated emodin (400 mg/kg)-induced hepatotoxicity in mice following three weeks of co-administration. Transcriptomic profiling and validation experiments demonstrated that activation of the NF-κB/NLRP3 signaling axis contributes to emodin-induced hepatic injury. Metabolomic analyses further revealed perturbations in key pathways, including lipopolysaccharide (LPS) biosynthesis, sphingolipid metabolism, and cholesterol metabolism. Integrated multi-omics analysis identified a significant positive correlation between these metabolites (LPS, sphingosine, cholesterol) and NF-κB/NLRP3 pathway genes. These findings suggest that emodin-mediated upregulation of LPS, sphingosine, and cholesterol activates the NF-κB/NLRP3 pathway, subsequently triggering hepatic injury. Collectively, this study delineates the metabolic detoxification routes of emodin and provides mechanistic insight into its hepatotoxic potential.

大黄素是一种富含中草药的生物活性化合物，具有广泛的治疗潜力，但由于相互矛盾的肝毒性报道而引起了安全性问题。本研究探讨了大黄素所致肝损伤的毒理学机制。大黄素（25-100 μM）对HepG2细胞产生剂量依赖性的细胞毒性，细胞色素P450 （CYP）酶CYP1A2和CYP3A4是将大黄素代谢成羟基化产物（M1-M3）的主要酶。大黄素及其代谢物在HepG2细胞中的毒性比较实验表明，cypp介导的代谢是一个重要的解毒途径。此外，1-氨基苯并三唑（ABT, 500 μM）抑制CYP可显著增强大黄素（12.5 ~ 100 μM）对HepG2细胞的毒性。同样，联合给药三周后，ABT （50 mg/kg）显著加重了大黄素（400 mg/kg）诱导的小鼠肝毒性。转录组学分析和验证实验表明，NF-κB/NLRP3信号轴的激活有助于大黄素诱导的肝损伤。代谢组学分析进一步揭示了关键通路的扰动，包括脂多糖（LPS）生物合成、鞘脂代谢和胆固醇代谢。综合多组学分析发现，这些代谢物（LPS、鞘氨醇、胆固醇）与NF-κB/NLRP3通路基因之间存在显著正相关。这些发现表明，大黄素介导的LPS、鞘氨醇和胆固醇的上调激活了NF-κB/NLRP3通路，随后引发肝损伤。总的来说，本研究描述了大黄素的代谢解毒途径，并提供了其肝毒性潜力的机制见解。

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引用次数: 0

Thalidezine triggers Cathepsin B-mediated cell death in T-cell lymphoma by disrupting lysosomal function 他利地嗪通过破坏溶酶体功能触发组织蛋白酶b介导的t细胞淋巴瘤细胞死亡。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-21 DOI: 10.1016/j.cbi.2026.111932

Yingjie Qing , Su Xu , Dawei Yang , Jie Liu , Hui Cao

T-cell lymphoma (TCL) is an aggressive malignancy defined by poor prognosis and therapeutic resistance, demanding innovative strategies. Targeting the lysosome to induce cell death has emerged as a powerful anti-cancer strategy, however its potential as a therapeutic target in TCL is yet to be fully developed. Here we report that Thalidezine (Tha) is a new and highly selective lysosomotropic agent (LA) with strong activity against TCL. Thalidezine diminished the acidic pH, and more importantly, induced the lysosomal membrane permeabilization (LMP). This LMP was not a passive event; it triggered the immediate and critical release of the protease Cathepsin B (CTSB) from the lysosomal lumen. We demonstrate that this cytosolic CTSB is the key executioner, directly initiating the apoptotic cascade through caspase-3 activation. Remarkably, CTSB knockdown rescued TCL cells from Tha-induced death, confirming that the CTSB-caspase axis constitutes the major death axis. Furthermore, Tha demonstrated significant in vivo efficacy in TCL cells-bearing NOD/SCID mice. In conclusion our results reveal Tha is a novel potent drug candidate and uncover a defined mechanism by weaponizing lysosomes to release CTSB, thereby establishing a therapeutically relevant vulnerability in TCL.

t细胞淋巴瘤（TCL）是一种预后差、治疗耐药的侵袭性恶性肿瘤，需要创新的治疗策略。靶向溶酶体诱导细胞死亡已成为一种强有力的抗癌策略，但其作为TCL治疗靶点的潜力尚未得到充分开发。本文报道了Thalidezine （Tha）是一种新型的高选择性溶酶收缩剂（LA），具有很强的抗TCL活性。他利得嗪降低了酸性pH值，更重要的是诱导了溶酶体膜透性（LMP）。这次LMP不是一个被动事件；它触发了蛋白酶组织蛋白酶B （CTSB）从溶酶体腔内的立即和关键的释放。我们证明这种细胞质CTSB是关键的刽子手，通过caspase-3激活直接启动凋亡级联。值得注意的是，CTSB敲低可使TCL细胞免于tha诱导的死亡，证实CTSB-caspase轴是主要的死亡轴。此外，它在携带TCL细胞的NOD/SCID小鼠体内显示出显著的功效。总之，我们的研究结果揭示了Thalidezine是一种新的有效的候选药物，并揭示了一种明确的机制-溶酶体武器化释放ctsb作为TCL治疗相关的脆弱性。

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引用次数: 0

Molecular mechanisms of Aflatoxin B1-Induced renal injury and the detoxification potential of Taraxasterol: A review 黄曲霉毒素b1致肾损伤的分子机制及Taraxasterol解毒潜力的研究进展。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-21 DOI: 10.1016/j.cbi.2026.111936

Chenyuan Wang , Xinyu Zhao , Yansong Wang , Hanshuo Li , Yun Shi , Yilong Cui

Aflatoxins (AFs) are carcinogenic toxin metabolites produced by Aspergillus fungi in humid environments. They are widely distributed in nature and pose threats to human and animal health as well as crop production. Among the 21 identified AFs, aflatoxin B₁ (AFB₁) is classified as a natural Group I carcinogen by the World Health Organization. The kidneys are the primary target organs for AFB₁ toxicity, and the underlying mechanism involves oxidative stress, mitochondrial damage, dysfunction of mitophagy, inflammatory injury, and cell apoptosis. Taraxasterol (TAR) is a natural extract with antioxidant, anti-inflammatory, and immunomodulatory effects, which can alleviate the damage caused by AFB₁ by acting on these pathways. Therefore, this review focuses on the current toxic mechanism of AFB₁-induced kidney injury and deeply explores the potential mechanism of TAR in alleviating its toxicity, providing a reference for the application of AFB₁ detoxification.

黄曲霉毒素（AFs）是曲霉真菌在潮湿环境中产生的致癌毒素代谢物。它们在自然界广泛分布，对人类和动物健康以及作物生产构成威胁。在已确定的21种AFs中，黄曲霉毒素B1 （AFB1）被世界卫生组织列为天然I类致癌物。肾脏是AFB1毒性的主要靶器官，其潜在机制涉及氧化应激、线粒体损伤、线粒体自噬功能障碍、炎症损伤和细胞凋亡。Taraxasterol （TAR）是一种具有抗氧化、抗炎和免疫调节作用的天然提取物，可以通过作用于这些途径来减轻AFB1引起的损伤。因此，本文就目前AFB1致肾损伤的毒性机制进行综述，深入探讨TAR减轻其毒性的潜在机制，为AFB1解毒的应用提供参考。

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引用次数: 0

In-vitro and in-vivo CYP3A4 Variants: Neratinib metabolism and drug interaction risk 体外和体内CYP3A4变异：Neratinib代谢和药物相互作用风险

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-21 DOI: 10.1016/j.cbi.2026.111935

Zheyan Zhang , Xiaoyu Huang , Chen Gan , Shuman Xue , Yan He , Congcong Wen

To investigate the effects of metabolic enzyme activity inhibition and genetic polymorphisms on the pharmacokinetics and pharmacodynamics of neratinib, we employed a combined approach of molecular docking and an in-vitro enzymatic reaction system to identify potential inhibitors in this study. The levels of neratinib and its metabolite were quantified using ultra performance liquid chromatography with tandem mass spectrometry. Additionally, in-vivo studies were conducted using Female Sprague-Dawley rats, and subsequent metabolic enzyme kinetics analyses were performed to evaluate the impact of genetic polymorphisms on neratinib metabolism. Among the 10 drugs screened, the antihistamine loratadine showed a pronounced inhibitory effect on neratinib metabolism in vitro, with a relative inhibition rate of 94.3 %, significantly increasing the systemic exposure of neratinib in rats. This finding is attributed to the mixed-type inhibition of liver microsome activity by loratadine. Furthermore, the differential inhibitory effects of loratadine toward CYP3A4.1 and CYP3A4.34 underscore the role of CYP3A4 genetic polymorphisms in modulating the inhibitory potency of loratadine toward neratinib. In conclusion, our study suggests that coadministration of loratadine and genetic polymorphisms in CYP3A4 can significantly influence neratinib metabolism, necessitating caution regarding potential drug-drug interactions in clinical settings.

为了研究代谢酶活性抑制和遗传多态性对纳拉替尼药代动力学和药理学的影响，本研究采用分子对接和体外酶反应体系相结合的方法来鉴定潜在的抑制剂。采用超高效液相色谱-串联质谱法定量测定奈拉替尼及其代谢物的含量。此外，使用雌性Sprague-Dawley大鼠进行体内研究，并进行随后的代谢酶动力学分析，以评估遗传多态性对neratinib代谢的影响。在筛选的10种药物中，抗组胺药氯雷他定对纳拉替尼体外代谢表现出明显的抑制作用，相对抑制率为94.3%，显著增加了大鼠对纳拉替尼的全身暴露。这一发现归因于氯雷他定对肝微粒体活性的混合型抑制。此外，氯雷他定对CYP3A4.1和CYP3A4.34的不同抑制作用强调了CYP3A4基因多态性在调节氯雷他定对neratinib的抑制效力中的作用。总之，我们的研究表明，氯雷他定和CYP3A4基因多态性共同给药会显著影响奈拉替尼的代谢，因此在临床环境中需要注意潜在的药物-药物相互作用。

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引用次数: 0

Prenatal hydroxychloroquine exposure-induced morphological and functional changes in multiple organs of fetal mice and its characteristics 产前羟氯喹暴露对胎鼠多器官形态和功能的影响及其特征。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-21 DOI: 10.1016/j.cbi.2026.111927

Yifan Liu , Lingbo Rong , Ailikaiti Aihemaitijiang , Xiaoqi Zhao , Wen Zhang , Hui Wang

Hydroxychloroquine is clinically widely used in the treatment of various autoimmune diseases and is one of the drugs that can be used throughout pregnancy. However, studies have suggested that prenatal hydroxychloroquine exposure (PHE) may affect early development of offspring, but a systematic and comprehensive evaluation is still lacking. Based on clinical medication regimens, this study administered hydroxychloroquine at different doses (20, 40, 80 mg/kg·d) to pregnant mice via oral gavage throughout gestation, aiming to observe changes in pregnancy outcomes, blood phenotypes of mothers and fetuses, and morphological and functional development of multiple fetal organs, as well as to explore the potential mechanisms.Results showed that PHE increased resorbed fetuses, stillbirths, and IUGR, and altered multiple blood indicators with the changes being particularly significant in feteses. The multi-organ functions were changed, inhibiting long bone and kidney development, adrenal steroid synthesis, placental trophoblast syncytialization, and promoting alveolar surfactant and hepatic bile acid synthesis, with females more affected gender differences and dose-effect relationship. Morphology confirmed abnormalities in long bones, gonads, and lungs. Correlation analysis showed multi-organ functional changes in females positively correlated with autophagy and apoptosis. This study confirms PHE causes adverse outcomes and abnormal multi-organ development, possibly via inhibited autophagy and increased apoptosis. This study has deepened our understanding of the developmental toxicity of hydroxychloroquine and provided experimental evidence for long-term hazard assessment and early prevention.

羟氯喹在临床上广泛应用于各种自身免疫性疾病的治疗，是妊娠期间可使用的药物之一。然而，有研究表明，产前羟氯喹暴露（PHE）可能影响子代早期发育，但仍缺乏系统和全面的评价。本研究在临床给药方案的基础上，通过妊娠期灌胃给予不同剂量（20、40、80 mg/kg·d）羟氯喹，观察其对妊娠结局、母胎血液表型、胎儿多器官形态功能发育的影响，并探讨其作用机制。结果显示，PHE增加了吸收胎儿、死产和IUGR，并改变了多项血液指标，其中以胎儿的变化尤为显著。多器官功能发生改变，抑制长骨和肾脏发育、肾上腺类固醇合成、胎盘滋养细胞合胞，促进肺泡表面活性物质和肝胆汁酸合成，且女性更受性别差异和剂量效应关系的影响。形态学证实长骨、性腺和肺部异常。相关分析显示，女性多器官功能变化与自噬和细胞凋亡呈正相关。本研究证实PHE可能通过抑制自噬和增加细胞凋亡导致不良后果和多器官发育异常。本研究加深了我们对羟氯喹发育毒性的认识，为长期危害评估和早期预防提供了实验依据。

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引用次数: 0

Corrigendum to “Biogenic Ag/AgCl nanocomposites induce apoptosis via mitochondrial pathway and reduce size of 3D HT29 colorectal cancer spheroids” [Chemico-Biological Interactions 421(2025) 111759] “生物源Ag/AgCl纳米复合材料通过线粒体途径诱导细胞凋亡并减小3D HT29结直肠癌球体的大小”的更正[化学-生物相互作用]21(2025)111759]。

IF 5.4 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Chemico-Biological Interactions

Pub Date : 2026-01-20 DOI: 10.1016/j.cbi.2026.111924

Gokhan Gorgisen , Cigdem Aydin Acar

引用次数: 0