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Research diversity and advances in simultaneous removal of multi-mycotoxin 同时去除多种霉菌毒素的研究多样性和进展。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-19 DOI: 10.1016/j.toxicon.2024.108106
Fred Mwabulili , Peng Li , Jinghao Shi , Hongxin Zhang , Yanli Xie , Weibin Ma , Shumin Sun , Yuhui Yang , Qian Li , Xiao Li , Hang Jia
Mycotoxins are toxic secondary metabolites produced by different fungal species under specific environmental conditions. The common and regulated mycotoxins are such as deoxynivalenol (DON), zearalenone (ZEN), ochratoxin (OTA), aflatoxin B1 (AFB1), and fumonisins (FB). These mycotoxins are highly regulated in feed and food because their effects start to exert from their lowest exposures and are abundant in our common environment. However, there are other emerging mycotoxins such as apicidin, beauvericin, aurofusarin, and enniatins which are also harmful. Thus, making a total of around 500 forms of mycotoxins. The existence of mycotoxins in feed and food has a significant impact on animal and human health, which ultimately, slows down economic growth globally. According to this review, different approaches to removing multi-mycotoxin separately or simultaneously have been stated. Mostly, the review focused on the simultaneous removal of different multiple mycotoxins. This is because the current studies show a growing trend in reporting the co-existence of multiple mycotoxins in feed and food materials, however, most detoxifying approaches are for singular mycotoxins. Therefore, the physical, chemical, and biological approaches to remove multi-mycotoxin have been elucidated as well as their advantages and limitations. Furthermore, the authors give suggestions on the way forward to reduce exposure to mycotoxins and diminish their health effects in society. Lastly, the authors emphasized introducing more stringent limits for co-existing mycotoxins, especially those that have the same health effects by acting synergistically, such as AFB1 and OTA, which both act as carcinogenic agents.
霉菌毒素是不同真菌物种在特定环境条件下产生的有毒次级代谢产物。常见和受管制的霉菌毒素包括脱氧雪腐镰刀菌烯醇(DON)、玉米赤霉烯酮(ZEN)、赭曲霉毒素(OTA)、黄曲霉毒素 B1(AFB1)和伏马菌素(FB)。这些霉菌毒素在饲料和食品中受到严格管制,因为它们的影响从最低接触量开始产生,而且在我们的常见环境中大量存在。不过,还有其他新出现的霉菌毒素,如芹菜素、贝维菌素、呋喃菌素和烯萘菌素,也对人体有害。因此,霉菌毒素的种类共有约 500 种。饲料和食品中霉菌毒素的存在对动物和人类健康产生了重大影响,最终导致全球经济增长放缓。根据这份综述,人们提出了分别或同时去除多种霉菌毒素的不同方法。综述主要侧重于同时去除不同的多种霉菌毒素。这是因为目前的研究表明,饲料和食品原料中同时存在多种霉菌毒素的报告呈上升趋势,但大多数解毒方法都是针对单一霉菌毒素的。因此,作者阐明了去除多种霉菌毒素的物理、化学和生物方法及其优势和局限性。此外,作者还就今后如何减少霉菌毒素的摄入量并降低其对社会健康的影响提出了建议。最后,作者强调要对同时存在的霉菌毒素实行更严格的限制,特别是那些通过协同作用对健康产生相同影响的霉菌毒素,如 AFB1 和 OTA,它们都是致癌物质。
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引用次数: 0
Venom-induced myocarditis: An unusual case attributable to Vipera aspis bite 毒液诱发的心肌炎:蝰蛇咬伤导致的不寻常病例
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-18 DOI: 10.1016/j.toxicon.2024.108104
Stefano Maffè, Paola Paffoni, Emanuela Facchini, Luca Bergamasco, Eleonora Prenna, Sara Ariotti, Anna Maria Paino, Stefano Ticozzi, Chiara Anchisi, Pierfranco Dellavesa

Venomous bites are medical emergencies that may result in life-threatening clinical effects. Cardiovascular complications are uncommon but they can be dangerous if not early detected and treated. Cerebral and myocardial infarction are described; myocarditis as consequence of viper envenomation in humans are very rare, almost anedoctal. We present the case of a 33-year-old man, working as keeper in a reptile zoo, who arrived after a viper bite of the Vipera aspis species, on the left wrist. The patient presented with clouded sensorium, edema of the lips and tongue, rapidly worsened with angioedema, and the need for oro-tracheal intubation; severe thrombocytopenia and anemia were treated with transfusions of platelet, plasma and red blood cells. The left hand and arm worsened, with compartment syndrome, treated with surgical fasciotomy. From a cardiological point of view, the patient presented a sudden drop in blood pressure, electrocardiographic anterior and infero-lateral ST depression, pericardial effusion and hypokinesia of the interventricular septum on echocardiography, and a significant increase in troponin T. Cardiac magnetic resonance imaging confirmed the myocarditis, with the presence of septal and anterior intramyocardial edema in T2 weighted sequences, with prolonged T2 time at T2 mapping analysis, without late gadolinium enhancement areas. Cardiological and general clinical conditions gradually improved only after the antivenom was administred. This is one of the rare cases of viper bite myocarditis with echocardiographic and magnetic resonance imaging documentation in Europe; it emphasizes the importance of identifying uncommon complications of venomous snake-bites and the prompt administration of antivenom, even though snake bites are less frequent at our latitudes.

毒液叮咬是一种医疗急症,可能导致危及生命的临床后果。心血管并发症并不常见,但如果不及早发现和治疗,也会很危险。脑梗塞和心肌梗塞已有描述;人类被毒蛇咬伤后引发心肌炎的情况非常罕见,几乎无临床表现。我们介绍了一例 33 岁男子的病例,他在一家爬行动物动物园担任饲养员,左手腕被蝰蛇咬伤。患者出现意识模糊、嘴唇和舌头水肿,并迅速恶化为血管性水肿,需要口气管插管;严重的血小板减少和贫血通过输注血小板、血浆和红细胞得到了治疗。左手和左臂病情恶化,出现室间隔综合征,通过外科筋膜切开术进行了治疗。从心脏病学角度来看,患者出现血压骤降、心电图前部和下外侧 ST 压低、心包积液、超声心动图显示室间隔运动减弱以及肌钙蛋白 T 明显升高。心脏磁共振成像证实了心肌炎,T2 加权序列显示室间隔和前心肌内水肿,T2 映射分析显示 T2 时间延长,无晚期钆增强区。只有在注射抗蛇毒血清后,心脏和全身临床状况才逐渐好转。这是欧洲罕见的一例有超声心动图和磁共振成像记录的蝰蛇咬伤性心肌炎病例;它强调了识别毒蛇咬伤的罕见并发症和及时注射抗蛇毒血清的重要性,尽管在我国纬度地区蛇咬伤并不常见。
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引用次数: 0
Evaluating the efficacy of botulinum toxin in treating complex regional pain syndrome: A systematic review 评估肉毒杆菌毒素治疗复杂性区域疼痛综合征的疗效:系统回顾
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-17 DOI: 10.1016/j.toxicon.2024.108100
Bruno Oliveira Almeida, Eduardo Silva Reis Barreto, Cesar Romero Antunes Júnior, Vinicius Borges Alencar, Anna Karla do Nascimento Souza, Liana Maria Torres de Araujo Azi, Liliane Elze Falcão Lins-Kusterer, Durval Campos Kraychete
Complex Regional Pain Syndrome (CRPS) is characterized by pain, swelling, limited range of motion, skin changes, vasomotor instability, and bone demineralization. This study aims to assess the efficacy of botulinum toxin type A (BoNT-A) in the treatment of CRPS. We conducted a systematic literature review following the PRISMA guidelines, using the PICO strategy (Patient, Intervention, Comparison and Outcome) with the following criteria: P = Patients with CRPS; I = Botulinum toxin; C = Placebo or active drug; and O = Pain relief. Three randomized controlled trials with placebo controls were included, involving a total of 64 patients, 36 of whom received BoNT-A in doses ranging from 40U to 200U. The studies examined both lumbar sympathetic block and local application methods. Botulinum toxin shows promise in alleviating pain associated with CRPS, particularly when used as an adjunct to lumbar sympathetic blockade. However, the limited number of studies and small sample sizes impede reaching definitive conclusions regarding its efficacy and safety. Notably, local applications (intradermal or subcutaneous) require further investigation, as current evidence is insufficient and reports indicate patient discomfort. While preliminary findings suggest potential benefits of BoNT-A in managing CRPS, larger randomized trials are necessary to confirm its efficacy and safety.
复杂性区域疼痛综合征(CRPS)的特点是疼痛、肿胀、活动范围受限、皮肤变化、血管运动不稳定和骨质脱钙。本研究旨在评估 A 型肉毒毒素(BoNT-A)治疗 CRPS 的疗效。我们遵循 PRISMA 指南,采用 PICO 策略(患者、干预、比较和结果)进行了系统性文献综述,标准如下:P = CRPS 患者;I = 肉毒杆菌毒素;C = 安慰剂或活性药物;O = 疼痛缓解。三项随机对照试验均以安慰剂为对照,共涉及 64 名患者,其中 36 人接受了剂量从 40U 到 200U 不等的 BoNT-A。这些研究同时考察了腰交感神经阻滞和局部应用方法。肉毒杆菌毒素有望缓解 CRPS 相关疼痛,尤其是作为腰交感神经阻滞的辅助治疗。然而,由于研究数量有限且样本量较小,因此无法就其疗效和安全性得出明确结论。值得注意的是,局部应用(皮内或皮下)需要进一步调查,因为目前的证据不足,而且有报告显示患者会感到不适。虽然初步研究结果表明 BoNT-A 对治疗 CRPS 有潜在的益处,但仍需进行更大规模的随机试验来确认其疗效和安全性。
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引用次数: 0
Algal extracts evaluation as an Antitoxicity sustainable solution against aflatoxin B1 toxicity in rat tissues 评估海藻提取物作为抗黄曲霉毒素 B1 在大鼠组织中的毒性的可持续解决方案
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-14 DOI: 10.1016/j.toxicon.2024.108098
Diaa Attia Marrez , Ahmed Noah Badr , Amanallah El-Bahrawy , Mohamed Ahmed Naeem

Aflatoxin B1 (AFB1) is a pre-carcinogenic molecule produced by toxigenic fungi and is widely harmful to public health. Algae extracts are sub-cellular pilot plants rich in bioactive substances that aid detoxification. This study aimed to reduce AFB1-toxicity in biological tissues of administrated rats using two algae extracts, Spirulina (SPR) and Amphora (AMR). Algae extracts were prepared using an aqueous system, concentrated, and lyophilized before being administrated to rats. The extract contents of total phenolic and flavonoids were determined to indicate their bioactive content and antioxidant potency. The animal experiment was designed in 8 groups as the control negative and control positive (AFB1; 20 μg/kg BW/day); groups 3 and 4 were designed for control positive of algae applied at high doses for toxicity evaluation. Otherwise, four groups were classified as G5 and G6 for rats administrated by AFB1, followed by 50 and 100 mg/kg Spirulina extract, respectively. The G7 and G8 were administrated with an AFB1 dose followed by amphora treatment at 50 and 100 mg extract/kg, respectively. The results showed a significant content of algae extracts of phenolic compounds (27.36 ± 1.75 and 39.55 ± 1.14 mg GAE/g DW for the SPR and AMR, respectively), with a valuable antioxidant activity. For rats treated only with the SPR or AMR extracts, no tissue changes were recorded for the liver, kidney, pancreas, or testis. Again, the biochemical parameters of these groups are recorded without harmful impacts, particularly for the tumor markers of AFP, TNF-α, CEA, and ALP. Once more, a higher extract concentration was more effective in AFB1-toxicity reduction, particularly for the SPR on the liver and kidney tissues. The SPR extract manifested a protective impact in sensitive tissue against the AFB1 effect, particularly in the testis. The results recommend the application of SPR extract at 100 mg/kg bw as an effective treatment for AFB1-toxicity regulation (as pharmaceutical or nutraceutical) involved in daily habits.

黄曲霉毒素 B1(AFB1)是一种由有毒真菌产生的致癌前分子,对公众健康普遍有害。藻类提取物是一种亚细胞先导植物,富含有助于解毒的生物活性物质。本研究旨在利用螺旋藻(SPR)和双子叶藻(AMR)这两种藻类提取物来降低给药大鼠生物组织中的 AFB1 毒性。藻类提取物采用水溶液体系制备,浓缩后冻干,然后给大鼠服用。提取物中总酚类和类黄酮的含量被测定,以显示其生物活性含量和抗氧化能力。动物实验设计了 8 组,分别为对照阴性组和对照阳性组(AFB1;20 μg/kg BW/天);第 3 组和第 4 组为对照阳性组,藻类以高剂量施用,进行毒性评估。另外,四组大鼠被分为 G5 和 G6 组,先服用 AFB1,然后分别服用 50 和 100 毫克/千克螺旋藻提取物。G7 和 G8 组大鼠先服用 AFB1,然后分别服用 50 和 100 毫克/千克的螺旋藻提取物。结果显示,藻类提取物中的酚类化合物含量很高(SPR 和 AMR 分别为 27.36 ± 1.75 和 39.55 ± 1.14 mg GAE/g DW),具有很高的抗氧化活性。仅使用 SPR 或 AMR 提取物处理的大鼠,其肝、肾、胰腺或睾丸组织均未发生变化。同样,这些组别的生化指标也没有受到有害影响,尤其是肿瘤标志物 AFP、TNF-α、CEA 和 ALP。此外,提取物浓度越高,对减少 AFB1 的毒性越有效,尤其是 SPR 对肝脏和肾脏组织的影响。SPR 提取物对敏感组织,尤其是睾丸,具有抗 AFB1 作用的保护作用。研究结果表明,100 毫克/千克体重的 SPR 提取物可作为日常生活习惯中调节 AFB1 毒性的有效疗法(作为药物或营养品)。
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引用次数: 0
Copper (II) increases anti-Proliferative activity of thymoquinone in colon cancer cells by increasing genotoxic, apoptotic, and reactive oxygen species generating effects 铜(II)通过增加基因毒性、细胞凋亡和活性氧生成效应,提高胸腺醌在结肠癌细胞中的抗增殖活性
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-13 DOI: 10.1016/j.toxicon.2024.108103
Vildan Betul Yenigun , Abdurrahim Kocyigit , Ebru Kanimdan , Ezgi Balkan , Ayse Zehra Gul

Thymoquinone is the main active compound derived from the essential oil of the Nigella sativa plant seed. While thymoquinone is an antioxidant, it has been reported in several studies that thymoquinone has dose-dependent pro-oxidant activity with the Fenton reaction in the presence of transition elements such as iron and copper. This study aimed to investigate cytotoxic, apoptotic, genotoxic, and reactive oxygen species (ROS) generating effects of thymoquinone treated with copper in colon cancer cells. HT-29 cells were treated with pro-oxidant-acting doses of thymoquinone alone and together with the non-toxic dose of Copper (II) Sulfate for 24 h. Cytotoxic, apoptotic, genotoxic, and ROS production activities were analyzed by MTT viability test, Acridine Orange/Ethidium Bromide (AO/EB) staining, alkaline single cell gel electrophoresis and H2DCF-DA assay, respectively. Viability results showed that thymoquinone and copper synergistically affect cancer cells, and DNA damage was increased with the synergic effect. The intracellular ROS was increased when thymoquinone and copper were applied together. Applying redox-active copper (II) with thymoquinone increases DNA damage, apoptosis, and cell death by increasing the amount of intracellular ROS through pro-oxidant activity. Treatments targeting copper-related pathways may open new therapeutic avenues for cancer treatment.

胸腺醌是从黑麦草种子精油中提取的主要活性化合物。虽然胸腺醌是一种抗氧化剂,但有多项研究表明,在铁和铜等过渡元素存在的情况下,胸腺醌与芬顿反应具有剂量依赖性的促氧化活性。本研究旨在探讨胸腺醌与铜处理结肠癌细胞的细胞毒性、凋亡、基因毒性和活性氧(ROS)生成效应。细胞毒性、细胞凋亡、基因毒性和 ROS 生成活性分别通过 MTT 活力测试、吖啶橙/溴化乙锭(AO/EB)染色、碱性单细胞凝胶电泳和 H2DCF-DA 检测进行分析。存活率结果表明,胸腺醌和铜对癌细胞有协同作用,DNA损伤随协同作用而加重。同时使用胸腺醌和铜时,细胞内的 ROS 增加。氧化还原活性铜(II)与胸腺醌一起使用会通过促氧化活性增加细胞内ROS的数量,从而增加DNA损伤、细胞凋亡和细胞死亡。针对铜相关途径的治疗方法可能会为癌症治疗开辟新的治疗途径。
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引用次数: 0
Quantitative assessment of Nigella sativa and conjugated silver nanoparticles against hexavalent chromium toxic effects on sperm function 定量评估黑麦草和共轭银纳米粒子对六价铬毒性对精子功能的影响
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-12 DOI: 10.1016/j.toxicon.2024.108102
Tooba Nauroze , Shaukat Ali , Shagufta Andleeb , Chaman Ara , Lubna Kanwal , Samaira Mumtaz , Muhammad Summer , Rizwan Ullah

Background

Infertility has been observed as one of the major issues in humans, one known risk factor is heavy metals.

Methods

The main focus of the present research was to assess the toxic effect of hexavalent chromium (Cr (VI)) on sperm and its mitigation by Nigella sativa seed extract (NS) and its conjugated silver nanoparticles (NS + NP). In the present study, we administered 1.5 mg/kg body of Cr (VI) orally in mice for 60 days routinely, to induce toxicity in testes and effect on sperm production and motility in male mice. NS and NS + NP (50 mg/kg body weight) were administered to evaluate protective action against Cr (VI). The sperm were analyzed by computer-assisted semen analysis (CASA) and chromium concentration in testicular tissue was measured via the atomic absorption spectrophotometer.

Results

The CASA analysis showed that Cr (VI) was directly linked with a decline in sperm concentration, motility, distance, velocity, straightness, and head beat frequency attributes. However, the administration of Nigella sativa seed extract and its green synthesized silver nanoparticles improved sperm concentration, motility, distance, velocity, straightness, and head beat frequency. The chromium content in the testes of Cr-exposed animals significantly increased, which negatively affected sperm parameters. However, Nigella sativa and Nigella sativa conjugated silver nanoparticles appeared to help in the removal of Cr content from testes hence improving the sperm parameters in exposed mice.

Conclusion

The decrease in Cr concentration improved sperm quality and quantity, hence, improve male fertility.

方法 本研究的重点是评估六价铬(Cr (VI))对精子的毒性作用,以及通过黑麦草种子提取物(NS)及其共轭银纳米粒子(NS + NP)来缓解这种作用。在本研究中,我们按常规给小鼠口服 1.5 mg/kg 体重的 Cr (VI),连续 60 天,以诱导雄性小鼠睾丸的毒性并影响精子的生成和活力。为了评估对六价铬的保护作用,小鼠还服用了 NS 和 NS + NP(50 毫克/千克体重)。通过计算机辅助精液分析(CASA)对精子进行了分析,并通过原子吸收分光光度计测量了睾丸组织中的铬浓度。然而,服用黑升麻籽提取物及其绿色合成的银纳米粒子可提高精子浓度、活力、距离、速度、直线度和头部跳动频率。铬暴露动物睾丸中的铬含量显著增加,对精子参数产生了负面影响。然而,黑麦草和黑麦草共轭银纳米粒子似乎有助于清除睾丸中的铬含量,从而改善暴露小鼠的精子参数。
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引用次数: 0
Exploring nematicidal biomolecules from Xenorhabdus nematophila as a novel source for Meloidogyne incognita management 探索从线虫中提取的杀线虫生物大分子,作为防治黑线蝇的新来源
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-12 DOI: 10.1016/j.toxicon.2024.108101
Deeikshana T , Poorniammal R , Shandeep S G , Vijay S , Prabhu S

Attempts were made to evaluate the purified bioactive compounds of Xenorhabdus nematophila against Meloidogyne incognita. In order to extract the purified compounds, a solid-supported liquid-liquid extraction system with a flow rate (1 mL/min) was used to purify bioactive molecules. Compounds were individually collected concentrated and evaluated against M. incognita. Among 25 fractions the L19 fraction, exhibited 98% inhibition in egg hatching and mortality of juveniles. The biomolecules were identified through Liquid Chromatography- Mass Spectroscopy (LC-MS) technique. To decipher the mode of action of compounds, molecular docking studies were performed with potential protein targets such as acetylcholinesterase, β-1,4-endoglucanase, glutathione S-transferase-1, cytochrome c oxidase, G-protein coupled receptor and Fatty acid and retinol-binding proteins of M. incognita. The results revealed that among eight compounds from the L19 fraction, malonate and pidopidon exhibited greater binding affinity towards the selected protein targets of M. incognita. In vitro studies with malonate and pidopidon against M. incognita showcased a 99% reduction in egg hatching and juvenile mortality. Moreover, greenhouse experiments revealed that malonate compounds not only reduced 94% of the M. incognita population but also enhanced the plant growth parameters in tomato by 60%. Hence the present study stands novel in exploiting the nematicidal compounds from X. nematophila giving limelight to explore pidopidon and malonate as novel nematicidal compounds for the management of M. incognita.

研究人员尝试评估纯化的 Xenorhabdus nematophila 生物活性化合物对 Meloidogyne incognita 的防治效果。为了提取纯化的化合物,使用了固体支撑液-液萃取系统,流速为 1 mL/min,以纯化生物活性分子。对化合物进行单独收集、浓缩并对 M. incognita 进行评估。在 25 个馏分中,L19 馏分对卵孵化和幼虫死亡率的抑制率为 98%。这些生物大分子通过液相色谱-质谱(LC-MS)技术进行了鉴定。为了破译化合物的作用模式,研究人员与潜在的蛋白靶标(如乙酰胆碱酯酶、β-1,4-内切葡聚糖酶、谷胱甘肽 S-转移酶-1、细胞色素 c 氧化酶、G 蛋白偶联受体以及麦蛾的脂肪酸和视黄醇结合蛋白)进行了分子对接研究。研究结果表明,在 L19 馏分的八种化合物中,丙二酸盐和匹多匹东对 M. incognita 的选定蛋白靶标具有更强的结合亲和力。利用丙二酸盐和pidopidon对M. incognita进行的体外研究显示,卵孵化率和幼虫死亡率降低了99%。此外,温室实验表明,丙二酸盐化合物不仅减少了 94% 的 M. incognita 数量,还提高了番茄植物生长参数的 60%。因此,本研究在利用 X. nematophila 的杀线虫化合物方面具有新颖性,为探索 pidopidon 和丙二酸盐作为新型杀线虫化合物管理 M. incognita 提供了机会。
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引用次数: 0
Multiple ventricular premature complexes following equatorial spitting cobra (Naja sumatrana) envenomation 赤道喷火眼镜蛇(Naja sumatrana)中毒后的多发性室性早搏综合征
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-10 DOI: 10.1016/j.toxicon.2024.108099
Kim Hoon Choo , Anisah binti Adnan , Ahmad Khaldun Ismail

Naja species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by Naja species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, Naja sumatrana bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom.

在马来西亚,Naja物种咬伤是最常见的远程虫媒传染咨询服务咨询原因。被眼镜蛇咬伤可能导致神经麻痹和心脏毒性反应,包括心律失常、高血压、心动过速、房室传导阻滞、室性心动过速和心室颤动。我们报告了一例被赤道喷吐眼镜蛇(Naja sumatrana)咬伤后早期表现为心脏毒性的病例,该病例在早期麻痹性中毒表现之前就出现了心脏毒性。一名 14 岁男孩因局部轻度中毒到急诊科就诊。心电图显示多发性室性早搏。随后患者出现上睑下垂。注射适当的抗蛇毒血清后,上睑下垂完全缓解,窦性心律恢复正常。住院两天后,患者康复出院。患者的心电图结果和神经毒性表现表明其为急性全身性蛇毒中毒。建议高度怀疑心脏毒性并进行密切的连续监测,以确保及时使用抗蛇毒血清。
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引用次数: 0
Obscure properties of a traditional herb Pittosporum neelgherrense used to treat snakebite envenoming against Daboia russelli venoms 用于治疗蛇咬伤的传统草药 Pittosporum neelgherrense 针对 Daboia russelli 毒液的不为人知的特性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-04 DOI: 10.1016/j.toxicon.2024.108089
M.D. Dinesh , Thirunavukkarasu P , Thulasi Sivaraman , K.V. Anju , Thushara James , Dhanusha J. Nair

In tropical nations, snakebite envenomation is a significant public health issue with negative human and social effects. This is due to three factors: 1) more species of the most hazardous snakes are present; 2) emergency medical assistance is not readily available; and 3) inadequate health care. The problems caused by snakebite envenomation have been partially resolved by immunotherapy. An extensive collection of medicinal herbs is recognized to have antivenomous properties in traditional medicine. However, very few species have undergone scientific investigation, and even fewer have had their active components separated and structurally and functionally defined. In this work, the anti-venom potential of hot and cold aqueous extracts from Pittosporum neelgherrense is evaluated using an in-vitro model. The experimental results showed that 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl-(11.20), 1-Undecanol (16.38), Lauryl acetate (18.25), and Cyclotridecane (19.14) were phytochemical substances whose chemical structures were recognized by GCMS. The Direct and Indirect hemorrhagic activity was found to be completely neutralized by P. neelgherrense extract (44.61% hot plant extract & 55.38% cold plant extract) and the zone (2.4 mm), respectively. The neutralization of venoms was indicated by the zone (0.5–0.9 cm) of hydrolysis production of proteolytic activity. Additionally, the results of the gelatine liquefaction study demonstrated that clot formation was not triggered by venom at low concentrations (50:50) but was instead brought on by higher concentrations. The present study suggested that the neutralization of venom by hot water extracts of P. neelgherrense is a potentially therapeutic application.

在热带国家,蛇咬伤是一个严重的公共卫生问题,对人类和社会造成负面影响。这是由于三个因素造成的:1) 存在更多种类的最危险蛇类;2) 无法随时获得紧急医疗救助;3) 医疗保健服务不足。免疫疗法已部分解决了蛇咬伤造成的问题。在传统医学中,大量药草被认为具有抗蛇毒的特性。然而,经过科学研究的药材种类很少,而将其有效成分分离出来并确定其结构和功能的药材更是少之又少。在这项研究中,我们利用体外模型评估了海桐的冷热水提取物的抗毒潜力。实验结果表明,4H-吡喃-4-酮、2,3-二氢-3,5-二羟基-6-甲基-(11.20)、1-十一烷醇(16.38)、月桂醇醋酸酯(18.25)和环十三烷(19.14)等植物化学物质的化学结构已被 GCMS 识别。结果表明,直接和间接出血活性完全被霓裳羽衣草提取物(44.61% 的热植物提取物和 55.38% 的冷植物提取物)中和,中和区域(2.4 毫米)也完全被霓裳羽衣草提取物中和。毒液的中和作用表现在蛋白水解活性的水解区(0.5-0.9 厘米)。此外,明胶液化研究结果表明,低浓度(50:50)毒液不会引发凝块的形成,相反,较高浓度的毒液会引发凝块的形成。本研究表明,通过热水萃取物中和鳗鲡毒液具有潜在的治疗用途。
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引用次数: 0
Structure-aided function assignment to the transcriptomic conopeptide Am931 转录组同肽 Am931 的结构辅助功能分配。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-03 DOI: 10.1016/j.toxicon.2024.108087
Shamasoddin Shekh , Shweta Dhannura , Pooja Dhurjad , Challa Ravali , Spoorti M M , Sreepriya Kakkat , Vishwajyothi , Marimuthu Vijayasarathy , Rajesh Sonti , Konkallu Hanumae Gowd

Implementation of the next-generation technologies for gene sequencing of venom duct transcriptome has provided a large number of peptide sequences of marine cone snails. Emerging technologies on computational platforms are now rapidly evolving for the accurate predictions of the 3D structure of the polypeptide using the primary sequence. The current report aims to integrate the information derived from these two technologies to develop the concept of structure-aided function assignment of Conus peptides. The proof of the concept was demonstrated using the transcriptomic peptide Am931 of C. amadis. The 3D structure of Am931 was computed using Density Functional Theory (DFT) and the quality of the predicted structure was confirmed using 2D NMR spectroscopy of the corresponding synthetic peptide. The computed structure of Am931 aligns with the active site motif of thioredoxins, possess catalytic disulfide conformation of (+, −)AntiRHHook and selectively modulate the N-terminal Cys3 thiol. These structural features indicate that Am931 may act as a disulfide isomerase and modulate the oxidative folding of conotoxins. Synthetic peptide Am931 provides proof-of-function by exhibiting catalytic activity on the oxidative folding of α-conotoxin ImI and improving the yield of native globular fold. The approach of integration of new technologies in the Conus peptide research may help to accelerate the discovery pipeline of new/improved conotoxin functional.

下一代毒液导管转录组基因测序技术的应用提供了大量海洋锥螺的多肽序列。计算平台上的新兴技术目前正在迅速发展,以利用主序列准确预测多肽的三维结构。本报告旨在整合从这两项技术中获得的信息,发展锥螺多肽的结构辅助功能分配概念。我们使用 C. amadis 的转录组多肽 Am931 验证了这一概念。使用密度泛函理论(DFT)计算了 Am931 的三维结构,并使用相应合成肽的二维核磁共振光谱证实了预测结构的质量。计算出的 Am931 结构与硫氧还蛋白的活性位点基序一致,具有 (+, -)AntiRHHook 的催化二硫构象,并可选择性地调节 N 端 Cys3 硫醇。这些结构特征表明,Am931 可作为一种二硫异构酶,调节芋螺毒素的氧化折叠。合成肽 Am931 在 α-conotoxin ImI 的氧化折叠过程中表现出催化活性,提高了原生球状折叠的产量,从而提供了功能证明。将新技术融入芋螺肽研究的方法可能有助于加速发现新的/改进的芋螺毒素功能。
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引用次数: 0
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