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Formulation and Evaluation of Polymeric Nanoparticles as Carriers of Rosuvastatin Calcium for Oral Administration 作为瑞舒伐他汀钙口服载体的聚合物纳米颗粒的制备与评估
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-10 DOI: 10.18311/ti/2023/v30i4/33447
M. Thenmozhi, T. Suganya, Gokul Marimuthu
Aim of this research was to formulate and evaluate the polymeric nanoparticle as carriers of rosuvastatin calcium for oral administration. Rosuvastatin calcium-loaded nanoparticles were formulated by nanoprecipitation method using different ratios of polymers (Eudragit L100 and Eudragit S100) and different concentrations of stabilizers (Pluronic F68 and PVA) with constant drug concentration. The formulations were evaluated for particle size, zeta potential, drug content, entrapment efficiency, in vitro release, kinetics, solubility, ex vivo intestinal permeability and Transmission Electron Microscopy (TEM). Fourier Transform-Infrared (FT-IR) spectroscopy and Differential Scanning Calorimetry (DSC) studies were carried out to check compatibility between the drug and polymers. No significant drug-polymer interactions were found. To enhance drug entrapment particle size range from 100-250 nm were prepared and entrapment efficiencies were found be 28-79 %. In vitro release studies showed a biphasic release pattern of rosuvastatin calcium from nanosuspensions: One initial burst release in the first 2 hours which could be helpful to improve the penetration of drug followed by a second slow release phase consistent with a Higuchi diffusion mechanism. The solubility of rosuvastatin calcium loaded polymeric nanoparticles compared to pure drug form was increased to about two-fold. Intestinal permeability of rosuvastatin calcium entrapped in Eudragit L100 an Eudragit S100 nanoparticles across rat small intestinal segments was significantly improved compared with rosuvastatin calcium in solution. Nanoparticles observed by TEM showed extremely spherical shapes. Results indicated that nanoparticle formulations could be a promising delivery system for oral administration of rosuvastatin calcium with enhanced solubility, intestinal permeability and improved oral bioavailability.
本研究旨在配制和评估作为罗伐他汀钙载体的聚合物纳米粒,用于口服给药。采用纳米沉淀法,在药物浓度不变的情况下,使用不同比例的聚合物(Eudragit L100 和 Eudragit S100)和不同浓度的稳定剂(Pluronic F68 和 PVA)配制了罗苏伐他汀钙负载纳米粒子。对制剂的粒度、ZETA电位、药物含量、包埋效率、体外释放、动力学、溶解度、体内外肠渗透性和透射电子显微镜(TEM)进行了评估。还进行了傅立叶变换红外光谱(FT-IR)和差示扫描量热法(DSC)研究,以检查药物与聚合物之间的相容性。没有发现药物与聚合物之间有明显的相互作用。为了提高药物的包埋效果,制备了粒径范围为 100-250 nm 的颗粒,发现其包埋效率为 28-79%。体外释放研究表明,罗伐他汀钙从纳米悬浮剂中呈双相释放模式:在最初的 2 个小时内,药物会有一个初始的迸发释放阶段,这有助于提高药物的渗透性,随后是第二个缓慢释放阶段,这与樋口扩散机制相一致。与纯药物相比,负载聚合物纳米粒子的罗舒伐他汀钙溶解度提高了约 2 倍。与溶液中的罗伐他汀钙相比,Eudragit L100 和 Eudragit S100 纳米粒子中夹带的罗伐他汀钙在大鼠小肠中的渗透性明显提高。用 TEM 观察到的纳米颗粒呈极度球形。结果表明,纳米颗粒制剂可以提高溶解度、肠道渗透性和口服生物利用度,是一种很有前途的罗伐他汀钙口服给药系统。
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引用次数: 0
Optimization of Stability-Indicating HPLC Method for Analyzing Process Related Impurities of Penfluridol and Structural Elucidation of Stress Degradation Products by LCMS/MSucidation of Stress Degradation Products by LCMS/MS 优化用于分析五氟利多工艺相关杂质的稳定性指示高效液相色谱法,并通过 LCMS/MS 对应激降解产物进行结构阐释 通过 LCMS/MS 对应激降解产物进行结构阐释
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-06 DOI: 10.18311/ti/2023/v30i4/34033
Beram Adilakshmi, V. K. Rohini, T. Eswarlal, Ch. Lakshmi Prasanna, Venkateswara Rao Anna
This study focused on the development of a simple and sensitive HPLC method for resolution and quantification of process-related impurities of penfluridol and further assessment of forced degradation behavior of penfluridol. The chromatographic separation was achieved on XTerra™ C18 (250×4.6 mm, 5.0μm) column and UV detection at 245nm. The mobile phase comprises of methanol and tetrahydrofuran in 55:45 (v/v) as solvent A and acetonitrile and tetrahydrofuran in 80:20 (v/v) as solvent B. The 60:40 (v/v) composition of solvent A and B were pumped isocratically at 1.0mL/min. In the proposed conditions, the retention time identified as 5.29 min for penfluridol, 4.51 min, 9.95 min and 7.64 min respectively for impurity 1, 2 and 3 with acceptable system suitability. The method produces sensitive detection limit of 0.008μg/mL for impurity 1, 2 and 0.004 μg/mL for impurity 3 with calibration range of 25-150 μg/mL for penfluridol and 0.025-0.150 μg/mL for impurities. The drug was exposed to different stressed conditions (acid, base, peroxide, thermal and UV light) according to ICH Q1A (R2) guidelines. The Degradation Products (DPs) formed during the stress study was characterized by LCMS/MS in ESI positive mode and the possible structures of five DPs with possible degradation pathways were proposed. The outcomes of other validation studies were likewise satisfactory and proven adequate for regular analysis of penfluridol and its process-related impurities in bulk drug and pharmaceutical dosage forms and can also applicable for evaluation of stress degradation mechanism of penfluridol.
本研究的重点是开发一种简单灵敏的高效液相色谱法,用于分辨和定量与五氟利多工艺相关的杂质,并进一步评估五氟利多的强制降解行为。色谱分离采用 XTerra™ C18 (250×4.6 mm, 5.0μm) 色谱柱,紫外检测波长为 245nm。以甲醇和四氢呋喃(体积比为 55:45)为溶剂 A,乙腈和四氢呋喃(体积比为 80:20)为溶剂 B。在此条件下,五氟利多的保留时间为 5.29 分钟,杂质 1、2 和 3 的保留时间分别为 4.51 分钟、9.95 分钟和 7.64 分钟,系统适用性良好。杂质 1、2 和 3 的灵敏检出限分别为 0.008 μg/mL 和 0.004 μg/mL,校准范围分别为 25-150 μg/mL(五氟利多)和 0.025-0.150 μg/mL(杂质)。根据 ICH Q1A (R2) 指南,将药物暴露于不同的压力条件(酸、碱、过氧化物、热和紫外线)下。在应力研究过程中形成的降解产物(DPs)在 ESI 阳性模式下通过 LCMS/MS 进行了表征,并提出了五种 DPs 的可能结构和可能的降解途径。其他验证研究的结果同样令人满意,证明足以用于对散装药物和药物剂型中的五氟利多及其工艺相关杂质进行定期分析,也可用于评估五氟利多的应激降解机制。
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引用次数: 0
A Review on the Impact of Pesticide Toxicity on the Physiological and Behavioral Condition of Fish 农药毒性对鱼类生理和行为状况的影响综述
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/34317
Sayan Mandal, Basudev Mandal
Pesticides are an essential component of contemporary agriculture because they help keep unwanted insects and animals under control and boost crop yields. However, the widespread usage of pesticides has led to worries over the unexpected consequences that these chemicals have on non-target animals and ecosystems, particularly those that are aquatic. Fish, which play an essential role in aquatic food webs, are particularly vulnerable to the damaging effects of pesticides as a result of their direct contact with contaminated water bodies. The review covers acute and chronic pesticide effects on fish, including physiological and behavioral responses. It discusses population-level effects and biodiversity loss on fish reproduction, growth, development, immunological function, and locomotor activity. It also highlights pesticide toxicity’s long-term effects on fish populations. Pesticide exposure may also alter foraging behavior, competitive aptitude, and predation vulnerability, according to the review. Pesticides harm fish health by accumulating toxins, causing genetic defects, and upsetting the aquatic ecology. These effects put biodiversity in jeopardy and upset the food chain’s delicate balance, raising major environmental issues. It emphasizes the need for interdisciplinary research to better understand fish pesticide toxicity and guide environmental regulatory measures. Implementation of Integrated Pest Management (IPM) practices to ensure sustainable pesticide use in the environment. Use of non-chemical strategies such as crop rotation, natural predators, and resistant varieties. limit pesticide application to specific pests, thereby minimizing ecological damage and preserving ecosystem equilibrium. We can improve agriculture-aquatic biodiversity coexistence by supporting holistic pesticide management.
杀虫剂是当代农业的重要组成部分,因为它们有助于控制有害昆虫和动物,提高作物产量。然而,杀虫剂的广泛使用导致人们担心这些化学品会对非目标动物和生态系统,尤其是水生动物和生态系统造成意想不到的后果。在水生食物网中扮演重要角色的鱼类,由于直接接触受污染的水体,特别容易受到杀虫剂的破坏性影响。本综述涵盖了农药对鱼类的急性和慢性影响,包括生理和行为反应。它讨论了对鱼类繁殖、生长、发育、免疫功能和运动活动的种群效应和生物多样性损失。它还强调了农药毒性对鱼类种群的长期影响。综述指出,接触农药还可能改变觅食行为、竞争能力和捕食脆弱性。农药通过积累毒素、造成基因缺陷和破坏水生生态来损害鱼类健康。这些影响危及生物多样性,破坏食物链的微妙平衡,引发重大环境问题。报告强调需要开展跨学科研究,以更好地了解鱼类农药的毒性,并指导环境监管措施。实施有害生物综合管理(IPM)实践,确保环境中农药的可持续使用。使用轮作、天敌和抗性品种等非化学策略,将杀虫剂的使用限制在特定害虫上,从而最大限度地减少生态破坏,维护生态系统平衡。我们可以通过支持整体农药管理来改善农业-水生生物多样性共存的状况。
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引用次数: 0
Ameliorative Role of Allicin in Arsenic-Induced Liver and Gonad Apoptosis in Male Swiss Albino Mice (Mus musculus) 大蒜素对砷诱导的雄性瑞士白化小鼠肝脏和性腺凋亡的改善作用
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/34093
Payel Sarkar, Jayanta Kr. Kundu
Arsenic toxicity is a matter of concern in the present-day world. Arsenic, a potentially hazardous metalloid easily gets biomagnified through the food chain and also affects not only the vital organs such as the kidney, and liver of human beings but also the reproductive organs of males. This study was designed to propose allicin, the main bio-active component of garlic to address arsenic toxicity more efficiently and without any side effects apart from the costly conventional chelation therapy which is not free from various side effects. To conduct this study, allicin has been quantified and collected from ethanolic extract of garlic by High-Performance Liquid Chromatography (HPLC) using C18 column at 254nm wave-lengths against standard allicin at the retention time of 18.775min. The calculated concentration of allicin is 77.80%. Next, arsenic trioxide (As2O3) (20mg/kg) and allicin (100mg/kg) were administered orally for toxicity and treatment respectively in mice (Mus musculus) for 30 days. Compared to the control group, liver marker enzymes i.e., Serum Glutamic Pyruvate Transaminase (SGPT), Serum Glutamic Oxaloacetic Transaminase (SGOT), and Alkaline Phosphatase (ALP) levels were significantly increased in the arsenic-induced group. On the other hand, co-treatment with allicin significantly recovered liver enzyme parameters to normal levels (p<0.05). Decreased weight of testis, sperm count, and increased numbers of Sperm Head Anomalies (SHA) indicate reduced reproductive potential in the arsenic-induced group of male albino mice. On the contrary, co-treatment with allicin significantly increased testis weight, sperm count and decreased SHA count (p<0.05). On examining histological slides of the liver and testis, normal histo-architecture was observed in both control and arsenic-induced allicin co-treated groups; whereas damage was observed in the arsenic-induced group. Generated data pointed out that allicin offers significant protection to the mammalian liver and male gonad (testis) against arsenicinduced toxicity.
砷毒性是当今世界令人担忧的问题。砷是一种潜在危险的类金属,很容易通过食物链产生生物放大作用,不仅会影响人体的肾脏和肝脏等重要器官,还会影响男性的生殖器官。本研究旨在提出大蒜的主要生物活性成分大蒜素,以更有效、无副作用地解决砷中毒问题。为了进行这项研究,我们采用 C18 柱高效液相色谱法(HPLC)对大蒜乙醇提取物中的大蒜素进行了定量和收集,波长为 254 纳米,保留时间为 18.775 分钟,对照标准大蒜素。计算得出的大蒜素浓度为 77.80%。接着,给小鼠口服三氧化二砷(As2O3)(20 毫克/千克)和大蒜素(100 毫克/千克),分别进行为期 30 天的毒性试验和治疗。与对照组相比,砷诱导组的肝脏标志酶,即血清谷氨酸丙酮酸转氨酶(SGPT)、血清谷氨酸草酰乙酸转氨酶(SGOT)和碱性磷酸酶(ALP)水平明显升高。另一方面,与大蒜素联合治疗后,肝酶指标明显恢复到正常水平(p<0.05)。砷诱导组雄性白化小鼠的睾丸重量、精子数量减少,精子头部畸形(SHA)数量增加,表明其生殖潜力降低。相反,与大蒜素联合治疗可明显增加睾丸重量、精子数量,减少精子头部畸形(SHA)数量(p<0.05)。在检查肝脏和睾丸的组织切片时,对照组和砷诱导的大蒜素联合处理组都观察到正常的组织结构,而砷诱导组则观察到损伤。所产生的数据表明,大蒜素对哺乳动物的肝脏和雄性性腺(睾丸)具有显著的保护作用,可防止砷引起的毒性。
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引用次数: 0
Effect of Lead Toxicity on Wild Cannabis Species of Punjab Region 铅毒性对旁遮普地区野生大麻物种的影响
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/31022
Dimpy Balgotra, Sabreen Bashir, Agrataben Vadhel, Madhuri Girdhar, Anand Mohan
Human activities are causing environmental pollution in many ways by contaminating air, water and soil by adding different types of pollutants. Among various pollutants, heavy metals are an emerging threat in today’s world which are degrading our environment in a number of ways. Lead is the most widespread and evenly distributed poisonous element. Due to urbanization and growing human activities, lead emissions in different forms have increased, resulting in the contamination of soil and water. The lead transfers from environment to different forms of life, disrupting biological processes and causing various health issues. In this article, pot culture experiments were carried out to analyse the stress of Lead (Pb) and the capability of Cannabis sp. to tolerate the stress by studying the impact of different concentrations (0 mg/kg, 50 mg/kg, 100 mg/kg and 150 mg/kg of soil) on various biochemical aspects of the plant (Photosynthetic pigments, protein, antioxidant enzyme activity). Lead was given in the form of lead acetate. The results showed that the photosynthetic pigments-chlorophyll and carotenoid decreased with increasing lead concentration. Same effect was shown by the protein content in the leaves. On the other hand, Superoxide Dismutase (SOD), which is an antioxidant enzyme, increased with increasing concentration of lead.
人类活动通过添加不同类型的污染物污染空气、水和土壤,以多种方式造成环境污染。在各种污染物中,重金属是当今世界新出现的一种威胁,它正在以多种方式使我们的环境恶化。铅是分布最广泛、最均匀的有毒元素。由于城市化和人类活动的增加,以不同形式排放的铅有所增加,导致土壤和水受到污染。铅从环境中转移到不同形式的生物体内,破坏生物过程,导致各种健康问题。本文进行了盆栽培养实验,通过研究不同浓度(0 毫克/千克、50 毫克/千克、100 毫克/千克和 150 毫克/千克土壤)对植物各生化方面(光合色素、蛋白质、抗氧化酶活性)的影响,分析铅(Pb)的胁迫和大麻对胁迫的耐受能力。铅以醋酸铅的形式给予。结果表明,光合色素-叶绿素和类胡萝卜素随着铅浓度的增加而减少。叶片中的蛋白质含量也显示出同样的效果。另一方面,作为抗氧化酶的超氧化物歧化酶(SOD)随着铅浓度的增加而增加。
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引用次数: 0
Preclinical Animal Models of Renal Disease 肾病临床前动物模型
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/34635
Kunal Bahalkar, Manish Musale, J. Kakadiya
Acute Renal Failure (ARF) is a serious condition where the kidneys suddenly stop working, commonly caused by drug-related injury. This article aims to give a detailed explanation of different animal models used to study ARF, focusing on the biomarkers linked with this condition. When administering drugs to animals, it is essential to be mindful of the potential for ARF to occur. Nephrotoxic drugs like cisplatin, methotrexate, acyclovir, Cyclosporine, folic acid, amphotericin B, and amikacin can induce ARF if the dosage and duration of exposure are not adequately regulated to match the clinical scenario. Careful monitoring is crucial to ensuring the safety and well-being of the animals under our care. This article contains various screening models for ARF caused by various allopathic drugs like glycerol, acyclovir, amikacin, amphotericin B, Isoniazid-Rifampicin, cisplatin, folic acid, diclofenac, and lithium. The intrinsic toxicity of these medications also plays a significant role in the ensuing Acute Kidney Injury (AKI), and the kidney is probably more vulnerable to damage than other organs. These medications can be hazardous and their effects on the glomerulus and/or tubules can be caused by oxidative damage, hypersensitivity responses, altered hemodynamics, and tubule blockage. This article aims to provide a thorough description of the model used and to examine the findings in relation to that particular model. This approach can yield valuable insights and help ensure the findings’ accuracy and relevance.
急性肾功能衰竭(ARF)是肾脏突然停止工作的一种严重病症,通常由药物相关损伤引起。本文旨在详细解释用于研究急性肾衰竭的不同动物模型,重点介绍与该病症相关的生物标志物。在给动物用药时,必须注意发生 ARF 的可能性。顺铂、甲氨蝶呤、阿昔洛韦、环孢素、叶酸、两性霉素 B 和阿米卡星等肾毒性药物,如果剂量和接触时间没有根据临床情况进行适当调节,就会诱发 ARF。仔细监测对确保我们护理的动物的安全和健康至关重要。本文包含由各种对抗疗法药物(如甘油、阿昔洛韦、阿米卡星、两性霉素 B、异烟肼-利福平、顺铂、叶酸、双氯芬酸和锂)引起的 ARF 的各种筛选模型。这些药物的内在毒性也是导致急性肾损伤(AKI)的重要原因,肾脏可能比其他器官更容易受到损害。这些药物可能具有危害性,其对肾小球和/或肾小管的影响可由氧化损伤、超敏反应、血流动力学改变和肾小管阻塞引起。本文旨在对所使用的模型进行详尽的描述,并研究与该特定模型相关的发现。这种方法可以产生有价值的见解,并有助于确保研究结果的准确性和相关性。
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引用次数: 0
Prophylactic Efficacy of Allium sativum Essential Oil on Hepatic Tissues of Mice Model Exposed to Inorganic Lead Salt 薤白精油对暴露于无机铅盐的小鼠肝组织的预防性功效
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/32343
Kusum Sharma, Veena Sharma
Hypothesis: Lead is a pervasive environmental pollutant that is major threat for human health. Allium sativum essential oil could impart possible protection from Lead Nitrate (LN) as it contains organosulfur compounds which possess various pharmacological potential including antioxidant, anti-inflammatory, anticancer, anti-apoptotic and other activities as well. Parameters Studied: The ameliorative role of Allium sativum essential oil on hepatic tissue damage caused by Lead nitrate was evaluated through oxidative stress, biochemical parameters, oxidative Stress Index (OSI) and hepatic biomarkers. Methodology and Results: In this study, six groups of animals were taken. These groups were: control animals, toxicant treated animals (LN), LN + plant oil low and high dose treated animals, LN + silymarin treated animals and LN + vehicle oil control group. Lead nitrate exposure significantly decreased the antioxidant molecules mainly SOD, CAT, Gpx, GSH, GST, TPC and increased the lipid peroxidation content, Oxidative Stress Index (OSI), liver indices, Total Cholesterol Content (TCC) and biochemical parameters [ALT, AST, ALP] In addition to this, Lead nitrate increased the level of hepatic biomarkers such as cytp4502E1, 5’-nucleotidase, and γ-glutamyltranspeptidase and decreased the cytb5 content in hepatic tissues. Conclusion: Antioxidant activity of Allium sativum Essential Oil (ASEO) prevented oxidative stress and restored the level of liver indices, biochemical parameters, and hepatic biomarkers in Lead nitrate-intoxicated mice. Therefore, ASEO can be considered as a promising protective strategy against Lead nitrate-induced hepatotoxicity.
假设:铅是一种普遍存在的环境污染物,对人类健康构成重大威胁。薤白精油含有有机硫化合物,具有抗氧化、抗炎、抗癌、抗细胞凋亡等多种药理作用,因此可以保护人体免受硝酸铅(LN)的伤害。研究参数:通过氧化应激、生化参数、氧化应激指数(OSI)和肝脏生物标志物评估薤白精油对硝酸铅引起的肝组织损伤的改善作用。方法和结果:本研究选取了六组动物。这些组分别是:对照组、毒物处理组(LN)、LN + 植物油低剂量和高剂量处理组、LN + 水飞蓟素处理组和 LN + 车用油剂对照组。硝酸铅暴露明显降低了抗氧化分子(主要是 SOD、CAT、Gpx、GSH、GST、TPC),增加了脂质过氧化物含量、氧化应激指数(OSI)、肝脏指数、总胆固醇含量(TCC)和生化指标[ALT、AST、ALP]、谷氨酰转肽酶、谷氨酰转肽酶、谷氨酰转肽酶]等生化指标。此外,硝酸铅还能提高肝脏生物标志物的水平,如肝细胞4502E1、5'-核苷酸酶、γ-谷氨酰转肽酶,并降低肝组织中细胞b5的含量。结论薤白精油(ASEO)的抗氧化活性可防止氧化应激,恢复硝酸铅中毒小鼠肝脏指数、生化指标和肝脏生物标志物的水平。因此,ASEO 可被视为一种很有前景的保护策略,可防止硝酸铅诱导的肝毒性。
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引用次数: 0
Determination of Acute Toxicity and the Effect of Sub-Lethal Concentration of Quinalphos on Protein and Lipid Peroxidation in Oreochromis niloticus 测定喹硫磷的急性毒性和亚致死浓度对黑线鲈蛋白质和脂质过氧化的影响
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/33533
Chinnu Shaji, Suma M. Abraham, Joe Prasad Mathew
Quinalphos is an organophosphate used in agriculture that is considered to have potential hazardous effects on nontarget organisms. The present study was designed to determine the median lethal concentration (LC50) of quinalphos (an organophosphate pesticide) on the fish, Oreochromis niloticus, for 96 hours. The LC50 value of quinalphos on Oreochromis niloticus for 96 hours was determined as 3.65 μl/L. The study also focuses on the immediate effect of exposure to sub-lethal concentrations of quinalphos on protein and lipid peroxidation rate after 24 hours in brain and muscle tissues. Protein was found to be decreasing while lipid peroxidation rate increased in both tissues after 24 hours of exposure. By the estimation of antioxidant enzymes Superoxide Dismutase (SOD) and Catalase (CAT) activity, it was also identified that quinalphos is capable of impairing the antioxidant defense mechanism of the non-target organism and thereby increase the oxidative stress.
喹硫磷是一种用于农业的有机磷,被认为对非目标生物具有潜在的危险影响。本研究旨在确定喹硫磷(一种有机磷农药)对黑线鲈鱼 96 小时的中位致死浓度(LC50)。经测定,喹硫磷对黑线鲈 96 小时的半数致死浓度为 3.65 微升/升。研究还重点关注了接触亚致死浓度的喹硫磷 24 小时后对大脑和肌肉组织中蛋白质和脂质过氧化率的直接影响。研究发现,接触喹硫磷 24 小时后,两种组织中的蛋白质都在减少,而脂质过氧化率却在增加。通过估算抗氧化酶超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性,还发现喹硫磷能够损害非目标生物的抗氧化防御机制,从而增加氧化应激。
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引用次数: 0
Chemical Induce Polycystic Ovarian Syndrome-Preclinical Animal Models 化学物质诱导多囊卵巢综合征--临床前动物模型
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-11-03 DOI: 10.18311/ti/2023/v30i4/34636
Aakansha Mishra, J. Kakadiya
Polycystic ovarian syndrome is a complex endocrine disturbance that leads to hyperandrogenism, disruption in the functioning of the Hypothalamic-Pituitary-Ovary (HPO) axis and multiple cysts in ovaries. To understand and study different treatment approaches of polycystic ovarian syndrome, there are several chemical-induced animal models available that mimic polycystic ovarian syndrome. These animal models are designed to closely resemble the characteristic symptoms. Polycystic Ovarian Syndrome’s key characteristics are changes in gonadotropin and sex steroid hormone, ovarian morphology, and metabolic characteristics. Direct hormone-regulated animal models are frequently utilized to study PCOS. Rodent animal model is often used which aims to replicate the key feature of human PCOS. Various endocrine-disrupting chemicals also makes a major role in the development of PCOS. In order to bridge the gap between basic research and clinical application in the field of PCOS, PCOS-induced models are essential tools for improving our understanding of the illness and evaluating innovative therapies. The review discusses various animal models used to induced PCOS by various inducers such as aromatase inhibitor inducer (letrozole), androgen excess inducer (dihydrotestosterone, dehydroepiandrosterone, testosterone), estrogen-induced (estradiol valerate), antiprogesterone (mifepristone), monosodium-L-glutamate, bisphenol-A and tributyltin chloride. This article contributed to underlying the current understanding and provides you a complete review that overall covers various aspects, including the impact of chemical-induced models, which also includes changes in the morphology of ovaries, gonadotropin as well as, and alterations in the level of various sex steroid hormone profile. Additionally it explores the metabolic abnormalities caused by various chemical-inducers used to induce PCOS in animal. The objective of this review is to provide a comprehensive review about various chemical inducers which are responsible for the development of PCOS.
多囊卵巢综合征是一种复杂的内分泌紊乱,会导致雄激素过高、下丘脑-垂体-卵巢轴(HPO)功能紊乱和卵巢多发性囊肿。为了了解和研究多囊卵巢综合症的不同治疗方法,有几种化学诱导的动物模型可以模拟多囊卵巢综合症。这些动物模型的设计与特征性症状非常相似。多囊卵巢综合征的主要特征是促性腺激素和性类固醇激素、卵巢形态和代谢特征的变化。在研究多囊卵巢综合症时,经常使用直接调节激素的动物模型。啮齿类动物模型常用来复制人类多囊卵巢综合征的主要特征。各种干扰内分泌的化学物质在多囊卵巢综合症的发病中也起着重要作用。为了缩小多囊卵巢综合症领域基础研究与临床应用之间的差距,多囊卵巢综合症诱导模型是提高我们对该疾病的认识和评估创新疗法的重要工具。这篇综述讨论了通过芳香化酶抑制剂诱导剂(来曲唑)、雄激素过量诱导剂(双氢睾酮、脱氢表雄酮、睾酮)、雌激素诱导剂(戊酸雌二醇)、抗孕激素(米非司酮)、L-谷氨酸钠、双酚 A 和三丁基氯化锡等各种诱导剂诱导 PCOS 的各种动物模型。这篇文章对当前的认识做出了贡献,并为您提供了一篇完整的综述,整体上涵盖了各个方面,包括化学诱导模型的影响,其中还包括卵巢形态、促性腺激素以及各种性类固醇激素水平的变化。此外,它还探讨了用于诱导动物多囊卵巢综合症的各种化学诱导剂所引起的代谢异常。本综述旨在全面回顾导致多囊卵巢综合症发生的各种化学诱导剂。
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引用次数: 0
Sub-Acute Toxicity Study of Hydro-Alcoholic Extracts of Sansevieria cylindrica and Plumeria obtusa in Wistar Albino Rats Wistar 白化大鼠对圆柱桑和钝顶梅水醇提取物的亚急性毒性研究
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-10-31 DOI: 10.18311/ti/2023/v30i4/31062
S. Shewale, V. Undale, V. Addepalli, Vrushali Bhalchim, S. Desai, Vikas Wawale, M. Shelar, Shubham Padole, Shital Satone, Shweta Lembhe, S. Parekh, P. Pujari
Sansevieria cylindrica Bojer ex. Hook (Asparagaceae) and Plumeria obtusa L. (Apocynaceae) are useful traditional medicines. The present study assessed the toxicity of a combination of hydro-alcoholic extract of aerial parts of both these plants through repeat administration in Wistar albino rats. This study is an extension of an acute toxicity study, wherein female rats were orally administered with a single dose of 2000mg/kg of both plant extracts. Sub-acute toxicity of both plants (200 and 400 mg/kg p.o.) was studied by daily dosing of Wistar rats of both sexes for 28 days. Toxicity, mortality, body weight changes, food and water intake, and neurological assessments were recorded. Hematological, biochemical, and urine analysis was done before and after dosing on day 29. Absolute and relative organ weight and histological evaluation were performed on day 29. The acute toxicity study revealed no lethal effects indicating that LD50 is greater than 2000mg/ kg. The sub-acute study observed a significant increase (p < 0.05) in body weight, feed, and water intake. The body weight gain in rats from the treatment group was non-significant (p > 0.05) compared to the control group. A significant (p < 0.05) increase in lymphocytes, granulocytes, RBC, platelet, creatinine, albumin, triglycerides, and alkaline phosphatase were also observed. The evaluation of different neurobehavior parameters showed a significant increase (p < 0.05). Histopathological analysis showed mild liver distortion in male rats in both treatment groups. Most of the significant observations were considered incidental findings indicative of low toxicity of plant extract during long-term use.
Sansevieria cylindrica Bojer ex.Hook(天门冬科)和 Plumeria obtusa L.(天南星科)是有用的传统药物。本研究通过对 Wistar 白化大鼠重复给药,评估了这两种植物气生部分水醇萃取物组合的毒性。这项研究是急性毒性研究的延伸,在这项研究中,雌性大鼠口服了单剂量为 2000 毫克/千克的两种植物提取物。通过对雌雄 Wistar 大鼠进行为期 28 天的每日给药,研究了两种植物(200 毫克和 400 毫克/千克 p.o.)的亚急性毒性。对毒性、死亡率、体重变化、食物和水摄入量以及神经系统评估进行了记录。第 29 天用药前后进行了血液、生化和尿液分析。第 29 天进行了绝对和相对器官重量及组织学评估。急性毒性研究显示,半数致死剂量大于 2000 毫克/千克,没有致死效应。亚急性研究观察到大鼠体重、饲料和水的摄入量显著增加(p < 0.05)。与对照组相比,处理组大鼠的体重增加不明显(p > 0.05)。此外,还观察到淋巴细胞、粒细胞、红细胞、血小板、肌酐、白蛋白、甘油三酯和碱性磷酸酶明显增加(p < 0.05)。对不同神经行为参数的评估显示出显著的增加(p < 0.05)。组织病理学分析表明,两个治疗组的雄性大鼠肝脏都有轻微变形。大多数重要的观察结果被认为是偶然发现,表明植物提取物在长期使用过程中毒性较低。
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Toxicology International
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