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A novel zearalenone lactonase can effectively mitigate zearalenone-induced reproductive toxicity in gilts. 一种新型玉米赤霉烯酮内酯酶能有效减轻玉米赤霉烯酮对后备母猪的生殖毒性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-18 DOI: 10.1016/j.toxicon.2025.108257
Jun-Chao Song, Zhe Peng, Yan-Qi Ning, Alainaa Refaie, Cheng-Fei Wang, Meng Liu, Lv-Hui Sun

Zymdetox Z-2000 is a novel zearalenone (ZEN) lactonase produced by Bacillus subtilis that can biodegrade ZEN to hydrolyzed ZEN and decarboxylated hydrolyzed ZEN with much lower estrogenic activity. This study aims to evaluate the efficacy of Zymdetox Z-2000 in mitigating the adverse effects of ZEN on the growth performance and reproductive health of gilts. A total of 80 crossbred Landrace × Yorkshire gilts (9.82 ± 0.79 kg) were allocated into five groups and received a basal diet (BD; CON), BD supplemented with 0.4 mg/kg ZEN (ZEN), BD plus ZEN with 0.01% Zymdetox Z-2000 (ZEN-Zym), BD plus ZEN with 0.01% coated Zymdetox Z-2000 (ZEN-CoZym), and BD plus ZEN with 0.1% B. subtilis (ZEN-Bs), respectively, for 28 days. Compared to the CON group, ZEN treatment reduced the body weight gain of the gilts, increased vulva area and vaginal and uterus indices, and increased serum aspartate aminotransferase (AST) activity and estradiol (E2) concentration. ZEN treatment also induced ovaries histopathology changes, decreased the total antioxidant capacity (T-AOC) in uterus but increased T-AOC in ovaries, and increased ZEN concentration in stomach and duodenum than those of the CON group. Interestingly, dietary supplementation with the three products effectively alleviated these ZEN-induced adverse effects, as Zymdetox Z-2000 and coated Zymdetox Z-2000 showed better mitigating effects than B. subtilis. In conclusion, ZEN exposure impaired the growth and reproductive health of gilts, while dietary supplementation with Zymdetox Z-2000 and coated Zymdetox Z-2000 can effectively alleviate ZEN-induced reproductive toxicity in gilts.

Zymdetox Z-2000是一种由枯草芽孢杆菌产生的新型玉米赤霉烯酮(ZEN)内酯酶,可将ZEN生物降解为水解ZEN和脱羧水解ZEN,具有较低的雌激素活性。本研究旨在评价Zymdetox Z-2000在缓解ZEN对后备母猪生长性能和生殖健康不利影响方面的效果。选取80头长×大杂交后备母猪(体重9.82±0.79 kg),随机分为5组,分别饲喂基础饲粮(BD;BD + ZEN添加0.01% Zymdetox Z-2000 (ZEN- zym), BD + ZEN添加0.01%包被Zymdetox Z-2000 (ZEN- cozym), BD + ZEN添加0.1%枯草芽胞杆菌(ZEN- bs),分别处理28 d。与CON组相比,ZEN处理降低了母猪增重,增加了外阴面积、阴道和子宫指数,提高了血清天冬氨酸转氨酶(AST)活性和雌二醇(E2)浓度。与CON组相比,ZEN组卵巢组织病理学改变,子宫总抗氧化能力(T-AOC)降低,卵巢总抗氧化能力(T-AOC)升高,胃和十二指肠ZEN浓度升高。有趣的是,在饮食中添加这三种产品可以有效缓解zen引起的不良反应,其中Zymdetox Z-2000和被包衣的Zymdetox Z-2000的缓解效果优于枯草芽孢杆菌。综上所述,ZEN暴露会损害后备母猪的生长和生殖健康,而饲粮中添加Zymdetox Z-2000和包被Zymdetox Z-2000能有效减轻ZEN对后备母猪的生殖毒性。
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引用次数: 0
Simplifying traditional approaches for accessible analysis of snake venom enzymes. 简化蛇毒酶分析的传统方法。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-18 DOI: 10.1016/j.toxicon.2025.108255
Gisele Adriano Wiezel, Isadora Sousa de Oliveira, Eliane Candiani Arantes

Snake venoms enzymes affect diverse physiological mechanisms leading to effects such as inflammation, edema, hemolysis, and blood clotting disorders. In this report, we describe modifications to classical assays for assessing the enzymatic activity of snake venom phospholipase A2 (PLA2) and phosphodiesterase (PDE), including the adaptation of the PDE assay to an agar plate. A final staining step, using Stains-all®, was added to the PLA2 activity assay on an egg yolk-containing agar plate. Moreover, PDE activity was successfully and qualitative assed using an agar plate-immobilized bis-p-nitrophenyl-phosphate. The modified methods introduced in this study improve accessibility for a broader spectrum of researchers, enabling venom-related investigations in any laboratory setting, with special relevance for regions where snakebites are most prevalent.

蛇毒酶影响多种生理机制,导致炎症、水肿、溶血和凝血障碍等影响。在本报告中,我们描述了用于评估蛇毒磷脂酶A2 (PLA2)和磷酸二酯酶(PDE)酶活性的经典检测方法的改进,包括将PDE检测方法应用于琼脂平板。最后一个染色步骤,使用Stains-all®,加入到含有蛋黄的琼脂板上的PLA2活性测定。此外,用琼脂平板固定化双对硝基苯基磷酸成功地定性测定了PDE的活性。本研究中引入的改进方法提高了更广泛的研究人员的可及性,使在任何实验室环境中进行与毒液相关的调查成为可能,特别适用于蛇咬伤最普遍的地区。
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引用次数: 0
Co-administration of rifampicin and Boswellia serrata mitigates testicular toxicity caused by Aflatoxin B1. 利福平与锯齿鲍斯韦利亚联合用药可减轻黄曲霉毒素B1引起的睾丸毒性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-15 DOI: 10.1016/j.toxicon.2025.108238
Fatih Ahmet Korkak, Zeliha Keskin Alkaç, Gözde Arkalı, İbrahim Halil Güngör, Burak Fatih Yüksel, Canan Akdeniz İncili, Sadettin Tanyıldızı, Gürdal Dağoğlu

The current study was aimed to investigate the effect of rifampicin (Rif), a stimulator of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), on limiting the passage of AFB1 (Aflatoxin B1) into testicular tissue. The second objective was to examine the potential protective effects of Boswellia serrata extract (BSE), which exhibits a strong antioxidant capacity, alone or incombination with Rif against testicular damage induced by AFB1. A total of 49 male Sprague-Dawley rats were randomly divided into seven experimental groups as follows: control (placebo), Rif (10 mg/kg), BSE (500 mg/kg), AFB1 (0.75 mg/kg), AFB1+Rif, AFB1+BSE, and AFB1+Rif + BSE. The rats were administered AFB1, Rif, and BSE for seven days. The result of this study indicated that Rif decreased the amount of AFB1 permeating the testicular tissue by stimulating the expression of P-gp and BCRP. The administration of the combination of BSE and Rif resulted in a reduction of oxidative stress, apoptosis, improvement in sperm function parameters, and an increase in serum testosterone levels. These effects contributed to the improvement of impaired testicular structure. The result of this study revealed that the Rif can potentially serve as an efficacious therapeutic agent and the administration of BSE exhibited a reduction in testicular damage induced by AFB1. However, the combination of BSE and Rif provided more effective protection than using alone.

本研究旨在探讨利福平(rifampicin, Rif)作为p -糖蛋白(P-gp)和乳腺癌抵抗蛋白(BCRP)的刺激剂,在限制AFB1(黄曲霉毒素B1)进入睾丸组织中的作用。第二个目的是研究Boswellia serrata提取物(BSE)的潜在保护作用,它显示出强大的抗氧化能力,单独或与Rif联合抗AFB1引起的睾丸损伤。选取雄性sd大鼠49只,随机分为对照(安慰剂)、Rif (10 mg/kg)、BSE (500 mg/kg)、AFB1 (0.75 mg/kg)、AFB1+Rif、AFB1+BSE和AFB1+Rif+BSE 7个实验组。给大鼠注射AFB1、Rif和BSE 7天。本研究结果表明,Rif通过刺激P-gp和BCRP的表达,降低了AFB1渗透睾丸组织的量。BSE和Rif联合用药导致氧化应激、细胞凋亡减少,精子功能参数改善,血清睾酮水平升高。这些作用有助于改善受损睾丸结构。本研究的结果显示Rif可能作为一种有效的治疗药物,并且BSE的施用显示出由AFB1引起的睾丸损伤的减少。然而,BSE和Rif联合使用比单独使用提供更有效的保护。
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引用次数: 0
Acute Sophora alkaloid poisoning in Hong Kong. 香港发生急性苦参生物碱中毒。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-15 DOI: 10.1016/j.toxicon.2025.108251
Tsz Kit Chow, Rex Pui Kin Lam, Chi Keung Chan, Man Li Tse, Yibin Feng, Timothy Hudson Rainer

Sophora alkaloids, including matrine, oxymatrine, and sophoridine, are quinolizidines found in plants used in traditional Chinese medicine such as Sophora flavescens and Sophora tonkinensis. Reports on acute Sophora alkaloid poisoning in humans outside of mainland China are lacking. This study aimed to characterize the clinical presentations, management, and outcomes of acute poisoning involving Sophora alkaloids in Hong Kong. We conducted a retrospective study of patients who were reported to the Hong Kong Poison Control Centre from all public emergency departments (EDs) in Hong Kong for acute poisoning involving Sophora alkaloids. Exposure was confirmed by laboratories, and data were collected between July 1, 2008 and June 30, 2021. We also analyzed patient demographics, clinical, management, and outcome characteristics. Among the 83 cases analyzed, S. flavescens was the major source (77.1%) of Sophora alkaloids and excessive dose was common (39.0%). Most patients (90.4%) had minor effects. Common clinical presentations were dizziness (83.1%), vomiting (72.3%), and palpitations (32.5%). No acute liver or kidney injuries or adverse skin reactions were observed. Treatment was primarily supportive and no patients underwent gastrointestinal decontamination, organ support treatment, or renal replacement therapy. Most patients (74.7%) were observed in the ED and only one required close monitoring in a cardiac care unit for prolonged QT interval after concurrent ciprofloxacin use. In contrast to the intravenous administration of S. flavescens, no adverse skin reactions were seen after oral consumption. Hepatoxicity, reported in in vitro and animal studies, and isolated human case reports, was not observed. In conclusion, excessive dose of S. flavescens is a common cause of acute Sophora alkaloid poisoning. Although most patients had mild symptoms, discrepancies in clinical presentations resulting from different formulations and varied experimental/clinical conditions call for further studies to evaluate the real-world risks of skin reactions and hepatoxicity of Sophora alkaloids.

苦参生物碱,包括苦参碱、氧化苦参碱和苦参碱,是在中药中使用的植物中发现的喹啉类化合物,如苦参和东参。在中国大陆以外,关于人类急性苦参生物碱中毒的报道较少。本研究旨在探讨香港苦参生物碱急性中毒的临床表现、处理及结果。我们对香港所有公共急症科(EDs)向香港中毒控制中心报告的涉及苦参生物碱的急性中毒患者进行了回顾性研究。实验室证实了接触情况,并在2008年7月1日至2021年6月30日期间收集了数据。我们还分析了患者人口统计学、临床、管理和结局特征。83例患者中,苦参生物碱的主要来源为黄参(77.1%),过量的情况较多(39.0%)。大多数患者(90.4%)有轻微影响。常见的临床表现为头晕(83.1%)、呕吐(72.3%)和心悸(32.5%)。未见急性肝、肾损伤及皮肤不良反应。治疗主要是支持性的,没有患者接受胃肠净化、器官支持治疗或肾脏替代治疗。大多数患者(74.7%)在急诊科观察到,只有1例患者在同时使用环丙沙星后需要在心内科密切监测QT间期延长。与静脉给药相比,口服后未见皮肤不良反应。没有观察到体外和动物研究报告的肝毒性,以及孤立的人类病例报告。综上所述,过量的黄参是引起急性苦参生物碱中毒的常见原因。虽然大多数患者症状轻微,但不同配方和不同实验/临床条件导致的临床表现差异需要进一步研究,以评估苦参生物碱的皮肤反应和肝毒性的真实风险。
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引用次数: 0
Degradation of aflatoxin B1 in corn by water-assisted microwave irradiation and its kinetic. 水助微波辐照降解玉米黄曲霉毒素B1及其动力学研究。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-15 DOI: 10.1016/j.toxicon.2025.108239
Yaolei Zhang, Lingling Zhang, Xiaoxia Zhang, Cheng Zhao, Mengmeng Li, Erqi Guan, Yangyong Lv, Ke Bian

Aflatoxin B1 (AFB1) is a highly toxic, carcinogenic, teratogenic, and mutagenic mycotoxin commonly found in corn. In this work, water-assisted microwave irradiation (WMI1) was used to degrade AFB1 in corn, during which the influencing factors and kinetics of AFB1 degradation were also studied. The results showed that the degree of corn crushing, the heating rate of WMI, the temperature of WMI, the solid-liquid ratio, the initial content of AFB1 and the microwave power were all important factors affecting the degradation of AFB1. With the increase of WMI temperature, AFB1 content in corn, microwave power and the decrease of solid-liquid ratio, the degradation rate of AFB1 in corn by WMI rose continuously. Its maximum degradation rate was more than 90.6%. Meanwhile, the degradation kinetics of AFB1 in corn revealed that the degradation process of WMI followed a pseudo-first-order kinetic equation. It was demonstrated that water molecules not only acted as solvents for AFB1 but also actively participated in its degradation process within corn samples during WMI treatment. Consequently, the results indicated that WMI was an effective method for degrading AFB1 in corn.

黄曲霉毒素B1 (AFB1)是一种高毒性、致癌性、致畸性和诱变性真菌毒素,常见于玉米中。本研究采用水辅助微波辐照(WMI1)降解玉米中AFB1,研究了AFB1降解的影响因素和动力学。结果表明,玉米破碎程度、WMI加热速率、WMI温度、料液比、AFB1初始含量和微波功率都是影响AFB1降解的重要因素。随着WMI温度的升高、玉米中AFB1含量的增加、微波功率的增大和料液比的降低,WMI对玉米中AFB1的降解率不断升高。其最大降解率大于90.6%。同时,玉米中AFB1的降解动力学表明,WMI的降解过程符合准一级动力学方程。结果表明,在WMI处理过程中,水分子不仅作为AFB1的溶剂,还积极参与了AFB1在玉米样品中的降解过程。综上所述,WMI是一种有效的玉米AFB1降解方法。
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引用次数: 0
DOES A DIAGNOSTIC NERVE BLOCK PREDICT THE OUTCOME OF BOTULINUM TOXIN TREATMENT? A NARRATIVE REVIEW. 诊断性神经阻滞能预测肉毒杆菌毒素治疗的结果吗?叙述性评论
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-13 DOI: 10.1016/j.toxicon.2024.108226
Thierry Deltombe, Anthony B Ward

Botulinum toxin type A is a first line choice in the treatment of spastic muscle overactivity. However, targeting the muscles involved in the deformity with the appropriate dose as well as choosing the goal to achieve and predicting the expected results can be challenging. Diagnostic nerve block with anaesthetics rapidly and temporarily suppresses overactivity of the selected muscle allowing clinicians to identify the involved muscles and the potential improvement of botulinum toxin injections. This narrative review summarizes the predictive value of the diagnostic nerve block before botulinum toxin injections. In the case of a stiff knee gait, rectus femoris blockade seems to predict knee flexion and gait speed improvement, which is subsequently obtained after rectus femoris botulinum toxin injections, but underestimates improvements in balance. In the case of spastic equinovarus foot, tibial nerve block provides a greater reduction in spasticity. Diagnostic nerve block assessment prior to botulinum toxin type A injections leads to an increase in the number of injected muscles, in the dose per muscle and in the overall cumulative dose. Finally, diagnostic nerve block may help to increase the goal achievement rate. Further well conducted studies are necessary.

A型肉毒毒素是治疗痉挛性肌肉过度活动的首选药物。然而,用适当的剂量靶向与畸形有关的肌肉,以及选择要实现的目标和预测预期结果可能是具有挑战性的。诊断神经阻滞与麻醉迅速和暂时抑制过度活动选定的肌肉,使临床医生识别受损伤的肌肉和潜在的改善肉毒杆菌毒素注射。本文综述了肉毒毒素注射前诊断性神经阻滞的预测价值。在膝关节僵硬步态的情况下,股直肌阻断似乎预测膝关节屈曲和步态速度改善,这随后在股直肌肉毒杆菌毒素注射后获得,但低估了平衡的改善。在痉挛性马蹄内翻足的情况下,胫神经阻滞可以更大程度地减少痉挛。A型肉毒毒素注射前的诊断性神经阻滞评估导致注射肌肉数量、每块肌肉剂量和总累积剂量的增加。最后,诊断性神经阻滞可能有助于提高目标完成率。有必要进一步进行良好的研究。
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引用次数: 0
Exploring high molecular weight components in Tityus serrulatus venom. 探索蛇毒中的高分子量成分。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-11 DOI: 10.1016/j.toxicon.2025.108240
Nicoly Malachize Alano-da-Silva, Isadora Sousa de Oliveira, Iara Aimê Cardoso, Karla de Castro Figueiredo Bordon, Eliane Candiani Arantes

Our study identified high-molecular-weight compounds from Tityus serrulatus venom (TsV), and most of them have not yet been well explored. TsV was fractionated using FPLC system with different columns, analyzed by SDS-PAGE, and characterized by MALDI-TOF/TOF. Our study showed that TsV contains several high-molecular-weight compounds, including CRISPs, metalloproteinase and hyaluronidase. We show how these molecules can be obtained from TsV, enabling future studies about their molecular structures and biological actions, expanding knowledge about this venom.

本研究鉴定出了一些高分子量化合物,其中大部分尚未被充分开发。采用不同色谱柱的FPLC分离TsV, SDS-PAGE分析,MALDI-TOF/TOF表征。我们的研究表明,TsV含有多种高分子量化合物,包括CRISPs、金属蛋白酶和透明质酸酶。我们展示了如何从TsV中获得这些分子,从而使未来对其分子结构和生物作用的研究成为可能,扩大了对这种毒液的认识。
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引用次数: 0
An update on botulinum toxin treatment of painful diabetic neuropathy, post-traumatic painful neuropathy/neuralgia, post-herpetic neuralgia and occipital neuralgia. 肉毒杆菌毒素治疗疼痛性糖尿病神经病、创伤后疼痛性神经病/神经痛、疱疹后神经痛和枕神经痛的最新进展。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-10 DOI: 10.1016/j.toxicon.2025.108237
Bahman Jabbari, Ava Tohidian

The literature in botulinum toxin treatment for painful diabetic neuropathy (PDN), post traumatic neuralgia (PTN), postherpetic neuralgia (PHN) and occipital neuralgia (ON) was reviewed up to Oct 1st, 2024. Using the efficacy criteria set forth by the Assessment and Guideline subcommittee of the American Academy of Neurology, the current levels of efficacy for these conditions could be designated as followings: PDN: B (probably effective, two class II study), PTN: A (effective, two class I studies); PHN: A (effective, two class I studies), ON: (undetermined due to lack of blinded investigations). Due to the small number of patients in these studies, proof of efficacy requires conduction of controlled and blinded studies in large cohorts of patients with longer follow ups. Future prospects of botulinum therapy for these pain disorders were discussed along with the advantages of this mode of treatment over the current modes of treatment.

本文综述了截至2024年10月1日,肉毒杆菌毒素治疗疼痛性糖尿病神经痛(PDN)、创伤后神经痛(PTN)、带状疱疹后神经痛(PHN)和枕神经痛(ON)的文献。根据美国神经病学学会评估和指南小组委员会制定的疗效标准,目前对这些疾病的疗效水平可指定如下:PDN: B(可能有效,两项II级研究),PTN: A(有效,两项I级研究);PHN: A(有效,两项I类研究),ON(由于缺乏盲法研究而未确定)。由于这些研究中的患者数量较少,因此证明疗效需要在大量患者中进行对照和盲法研究,随访时间较长。讨论了肉毒杆菌治疗这些疼痛疾病的未来前景以及这种治疗模式相对于当前治疗模式的优势。
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引用次数: 0
Novel tryptophyllin peptides from Physalaemus centralis inhibit oxidative stress-induced endothelial dysfunction in rat aorta preparation. 新型中央泡浆菌色氨酸肽抑制氧化应激诱导的大鼠主动脉内皮功能障碍。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-10 DOI: 10.1016/j.toxicon.2025.108234
Ariane Nogueira, José Brango-Vanegas, Andreanne G Vasconcelos, Alex P Coleone, Éder A Barbosa, Daniel C Moreira, Maria da Gloria da Silva, Wanessa F Cabral, Jhones D Nascimento, José Vinícius de Sousa França, Daniel Dias Rufino Arcanjo, Filipe Camargo D A Lima, Augusto Batagin-Neto, Selma A S Kückelhaus, Guilherme D Brand, Alexandra Plácido, José Roberto S A Leite

Amphibian skin is a rich source of molecules with biotechnological potential, including the tryptophyllin family of peptides. Here, we report the identification and characterization of two tryptophyllin peptides, FPPEWISR and FPWLLS-NH2, from the skin of the Central Dwarf Frog, Physalaemus centralis. These peptides were identified through cDNA cloning and sequence comparison. FPWLLS-NH2 shares its primary structure with a previously identified peptide from the skin of Pelophylax perezi, named PpT-2. Another peptide, FPPEWISR, is novel and was named PcT-1. After solid-phase peptide synthesis, both peptides exhibited significant antioxidant activity, with PcT-1 and PpT-2 demonstrating ABTS radical scavenging capacities of 0.305 and 0.269 mg Trolox equivalents/mg peptide, respectively, and ORAC values of 0.319 and 0.248 mg Trolox equivalents/mg peptide. Additionally, PcT-1 and PpT-2 inhibited AAPH-induced hemolysis in human red blood cells, achieving a protection level comparable to Trolox at 0.2 mg/mL. In rat aorta preparations, both peptides partially restored acetylcholine-induced vasorelaxation following pyrogallol-induced oxidative stress, with a greater protective effect of PpT-2. Hemolytic activity assay indicated no cytotoxicity in human red blood cells, and tests on Galleria mellonella larvae confirmed their low toxicity in vivo. These findings highlight the biotechnological potential of PcT-1 and PpT-2 as antioxidant agents, paving the way for new therapeutic applications in combating oxidative stress-related diseases.

两栖动物的皮肤是具有生物技术潜力的分子的丰富来源,包括色氨酸肽家族。在这里,我们报道了从中央矮蛙(Physalaemus centralis)皮肤中鉴定和表征的两种色氨酸肽FPPEWISR和FPWLLS-NH2。通过cDNA克隆和序列比较鉴定了这些多肽。FPWLLS-NH2的初级结构与先前从佩罗彼亚皮中鉴定出的肽(称为pt -2)相同。另一种肽FPPEWISR是新的,被命名为PcT-1。固相肽合成后,两种肽均表现出显著的抗氧化活性,PcT-1和PpT-2的ABTS自由基清除能力分别为0.305和0.269 mg Trolox当量/mg肽,ORAC值分别为0.319和0.248 mg Trolox当量/mg肽。此外,PcT-1和PpT-2抑制aaph诱导的人红细胞溶血,达到与0.2 mg/mL的Trolox相当的保护水平。在大鼠主动脉制剂中,这两种多肽都能部分恢复乙酰胆碱诱导的血管松弛,其中PpT-2的保护作用更大。溶血活性测定表明对人红细胞无细胞毒性,对mellonella幼虫的体内试验证实其低毒性。这些发现突出了PcT-1和PpT-2作为抗氧化剂的生物技术潜力,为对抗氧化应激相关疾病的新治疗应用铺平了道路。
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引用次数: 0
Development of an ex vivo model to assess the impact of fumonisin B1 on swine intestinal morphology. 建立离体模型评估伏马菌素B1对猪肠道形态的影响。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-10 DOI: 10.1016/j.toxicon.2025.108249
Janine Alves Sarturi, Cristina Tonial Simões, Cristiane Rosa da Silva, Isadora Fabris Laber, Luara Medianeira de Lima Schlösser, Luriane Medianeira Carossi Leal, Guilherme Konradt, Daniele Mariath Bassuino, Carlos Augusto Mallmann

This study was conducted to assess the effects of fumonisin B1 (FB1) on the jejunum of pigs using a novel ex vivo model conducted in parallel with an in vivo trial. For the in vivo model, twelve male 28 to 70-days-old pigs were subjected to two treatments of six animals each: the control group, fed a basal diet (BD), and the FB1 group, fed the BD + 50 mg/kg FB1. At 70 days, the animals were slaughtered and one jejunal sample was collected from each pig for further histopathological analyses. Other four male pigs from the in vivo control treatment were slaughtered at 70 days for the ex vivo model. Four jejunal explants were collected from each pig, totaling 16 intestinal explants, which were subjected to two treatments, with 8 explants each, using an Ussing Chamber (UC) system: the control group, subjected to buffer solution (BS), and the FB1 group, subjected to BS + 50 mg/L FB1. Samples from in vivo and ex vivo models were analyzed for histopathological parameters and subjective intestinal assessments. The FB1 group presented lower (P < 0.05) villi height than the control group in both in vivo and ex vivo. A decrease (P < 0.05) in the villi number, crypt depth, enterocyte height and enterocyte nucleus size was also observed in the FB1 group ex vivo, with a higher severity score of lymphatic vessels dilation than the control (P = 0.0459). The FB1 group also tended to increase the goblet cells count (P = 0.0736) ex vivo as well as to decrease the crypt width (P = 0.0638) in vivo. The ex vivo model exhibited similar mean values and statistical responses to those observed in vivo, demonstrating its potential as an alternative approach for assessing the effects of mycotoxins in a reduced number of animals.

本研究采用一种新的离体模型和体内试验相结合的方法来评估伏马菌素B1 (FB1)对猪空肠的影响。在体模型选用12头28 ~ 70日龄雄性猪,分为2个处理,每组6只,对照组饲喂基础饲粮(BD), FB1组饲喂BD + 50 mg/kg FB1。第70天屠宰,每头猪取一份空肠样本作进一步的组织病理学分析。其余4头体内对照处理的公猪在70天屠宰,用于离体模型。每只猪收集4个空肠外植体,共16个,采用Ussing Chamber (UC)系统进行两种处理,每组8个外植体,对照组为缓冲液(BS), FB1组为BS + 50 mg/L FB1。对体内和离体模型样本进行组织病理学参数分析和主观肠道评估。FB1组在体内和离体绒毛高度均低于对照组(P < 0.05)。离体FB1组绒毛数量、隐窝深度、肠细胞高度和肠细胞核大小均明显减少(P < 0.05),淋巴管扩张严重程度评分高于对照组(P = 0.0459)。FB1组也有增加体外杯状细胞计数(P = 0.0736)和降低体内隐窝宽度(P = 0.0638)的趋势。离体模型显示出与体内观察到的相似的平均值和统计响应,表明其作为评估真菌毒素在减少动物数量中的影响的替代方法的潜力。
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