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Cadmium-Induced Perturbation of Spleen Redox Status: Therapeutic Role of Pumpkin Seed Protein Isolate 镉诱导脾脏氧化还原状态的扰动:南瓜籽分离蛋白的治疗作用
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-09-20 DOI: 10.18311/ti/2023/v30i3/32544
Siddhartha Singh, Oly Banerjee, Ishita Saha, Sudipta Kundu, Alak Kumar Syamal, Bithin Kumar Maji, Sandip Mukherjee
One of the major threats to humanity is from the exposure of heavy metals irrespective of its source. Cadmium is one of such heavy metals to which humans are exposed in their daily lives via food or environment. Regardless of this, there is no established or efficient way of recycling Cadmium. On the other hand, Pumpkin seeds have innumerable health aiding properties. The present study aims to understand the antioxidative and anti-inflammatory properties of Pumpkin Seeds Protein Isolate (PSPI) against Cadmium mediated oxidative stress in spleen. Twenty male albino rats were divided into four groups; Control, Cadmium treated, Cadmium treated and PSPI 1 supplemented, Cadmium treated and PSPI 2 supplemented. After completion of treatment period (21 days), oxidative stress parameters, ROS generation levels and proinflammatory cytokines were measured along with histopathological evaluations. PSPI supplementation was observed to have significant free radical scavenging activities as evidenced by decreased lipid peroxidation and nitric oxide generation simultaneously with increased glutathione level, activities of superoxide dismutase and catalase. Cadmium also caused an elevation in tumor necrosis factor and interleukin-6 as well as ROS generation levels which were substantially reduced upon supplementation with PSPI. Furthermore, cadmium-induced micro architectural changes in the spleen were also countered upon PSPI supplementation. In summary, both lower and higher doses of PSPI supplementation curtail the cadmium induced oxidative stress, ROS levels, proinflammatory cytokines and damage in the splenic tissue. The Results of this study necessitates further mechanistic study to establish key role of PSPI in amelioration of cadmium toxicity.
对人类的主要威胁之一是重金属的暴露,无论其来源如何。镉是人类在日常生活中通过食物或环境接触到的重金属之一。尽管如此,目前还没有确定的或有效的回收镉的方法。另一方面,南瓜籽有无数的健康辅助特性。本研究旨在了解南瓜籽分离蛋白(PSPI)对镉介导的脾脏氧化应激的抗氧化和抗炎作用。20只雄性白化大鼠分为4组;对照,镉处理,镉处理和PSPI 1补充,镉处理和PSPI 2补充。治疗期(21天)结束后,测量氧化应激参数、ROS生成水平和促炎细胞因子,并进行组织病理学评估。添加PSPI具有显著的自由基清除活性,可以降低脂质过氧化和一氧化氮的产生,同时提高谷胱甘肽水平、超氧化物歧化酶和过氧化氢酶的活性。镉还引起肿瘤坏死因子和白细胞介素-6以及ROS生成水平的升高,这些水平在补充PSPI后大大降低。此外,补充PSPI也可以抵消镉诱导的脾脏微结构变化。综上所述,低剂量和高剂量的PSPI补充均可减少镉诱导的氧化应激、ROS水平、促炎细胞因子和脾组织损伤。本研究结果需要进一步的机制研究,以确定PSPI在改善镉毒性中的关键作用。
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引用次数: 0
Safety Evaluation of a Traditional Medicinal Plant, <i>Flemingia vestita</i> Benth and Hooker in Swiss Albino Mice: An Acute and Sub-acute Toxicity Study 一种传统药用植物&lt;i&gt;花莲&lt;/i&gt;Benth和Hooker对瑞士白化小鼠的急性和亚急性毒性研究
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-09-20 DOI: 10.18311/ti/2023/v30i3/32175
Aparmita Das, Arun Kumar Yadav, Bishnupada Roy
Acute and sub-acute oral toxicity assessment of Flemingia vestita root-peel extract was performed in Swiss albino mice as per OECD guidelines 425 and 407. In acute toxicity test, mice were administered extract doses of 175, 550, and 1760 mg/ kg body weight (b.w.), and finally, 2000 mg/kg b.w., limit dose. The treated animals were observed for adverse signs or mortality for 14 days. In the sub-acute toxicity study, mice were divided into seven groups (n = 5). Animals in group one served as control, while group five received acetaminophen to act as positive control. Groups two, three and four of animals were given 75, 150 and 300 mg/kg doses of extract for 28 days. Animals in groups six and seven served as the satellite groups for 300 mg/kg and acetaminophen-treated groups for another two weeks to monitor any delayed effects or reversal from adverse effects. The study was approved by the Member-Secretary and the Chairman, Institutional Ethics Committee (Animal Models) of North-Eastern Hill University, Shillong vide letter number: IEC/MS/Misc./08/dated September 26, 2019. Body weight, relative organ weight, haematological and biochemical parameters, and histopathology of the liver, kidney, intestine and spleen of animals were studied. No adverse effects or mortality of animals was observed at 2000 mg/kg b.w., limit dose. The LD50 of the extract was estimated to be greater than 2000 mg/kg. In a sub-acute toxicity study, a 300 mg/kg dose showed a noticeable decrease in food, water consumption, and body weight. Likewise, haematological observations revealed an increase in leukocyte count, and biochemical parameters showed an increase in aspartate aminotransferase in 300 mg/kg extract dose. In histopathological studies, mildly disrupted hepatocytes were observed in liver sections of high-dose treated mice. The findings suggest that F. vestita root-peel extract is safe for consumption but may cause mild toxicity at a high dose of 300 mg extract/kg b.w.
根据OECD指南425和407,对瑞士白化小鼠进行了Flemingia vestita根皮提取物的急性和亚急性口服毒性评估。在急性毒性试验中,小鼠分别以175、550和1760 mg/kg体重(b.w)给药,最后以2000 mg/kg b.w给药。观察治疗动物的不良症状或死亡14天。亚急性毒性研究将小鼠分为7组(n = 5),第一组为对照组,第五组给予对乙酰氨基酚作为阳性对照。第2组、第3组和第4组分别给予75、150和300 mg/kg剂量的提取物,试验期28 d。第6组和第7组的动物作为300 mg/kg的卫星组,对乙酰氨基酚处理组再进行两周,以监测任何延迟效应或不良反应的逆转。本研究由东北山大学机构伦理委员会(动物模型)委员秘书兼主席批准,信号:IEC/MS/Misc。/08/日期2019年9月26日。对动物的体重、相对脏器重量、血液学和生化指标以及肝、肾、肠、脾的组织病理学进行了研究。2000mg /kg体重(极限剂量)未见不良反应或动物死亡。估计该提取物的LD50大于2000 mg/kg。在一项亚急性毒性研究中,300毫克/公斤的剂量显示出食物、水的消耗和体重的显著减少。同样,血液学观察显示白细胞计数增加,生化参数显示300 mg/kg剂量的天冬氨酸转氨酶增加。在组织病理学研究中,在高剂量处理小鼠的肝切片中观察到轻度破坏的肝细胞。研究结果表明,紫花苜蓿根皮提取物可安全食用,但在300 mg /kg b.w的高剂量下可能产生轻度毒性。
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引用次数: 0
Reverse Docking Approach Reveals the Negative Effect of Caffeine Toxicity on Glutamate GluR2 Receptor 反向对接方法揭示咖啡因毒性对谷氨酸GluR2受体的负面影响
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-09-20 DOI: 10.18311/ti/2023/v30i3/33446
Hasan Ansari, Prekshi Garg, Radhika Rastogi, Rekha Sharma, Prachi Srivastava
In the past decade, the consumption of caffeine has increased exponentially throughout the world. Caffeine is now not only limits to coffee but is present in several desserts and other beverages as well. Caffeine is a psychostimulant that helps in improving your performance but its excessive consumption can also affect the cognitive functions of the Central Nervous System (CNS) negatively. The present research is an attempt to understand the mechanism of caffeine action in blocking central nervous system receptors thereby affecting brain function adversely. The reverse docking approach of computational biology has been implied to visualize the interaction of several neurotransmitter receptors with caffeine. Reverse molecular docking is an approach for determining the effect of a ligand on a range of receptors. The binding energy of the receptors with caffeine is considered for determining the best receptor-ligand complex. A list of 7 different neurotransmitters was identified through a literature study and taken into consideration in the current research. The molecular interaction of the human neuro-receptors was seen with caffeine using AutoDock4.0 to study the impact of caffeine on several biological processes of the human brain. The molecular docking approach identifies glutamate gluR2 receptor to be adversely affected by caffeine toxicity thereby affecting the neurotransmission process in the human nervous system.
在过去的十年里,全世界咖啡因的消费量呈指数级增长。咖啡因现在不仅限于咖啡,而且存在于几种甜点和其他饮料中。咖啡因是一种精神兴奋剂,有助于提高你的表现,但过量摄入也会对中枢神经系统(CNS)的认知功能产生负面影响。本研究试图了解咖啡因阻断中枢神经系统受体从而对脑功能产生不利影响的机制。计算生物学的反向对接方法已经被用来可视化几种神经递质受体与咖啡因的相互作用。反向分子对接是一种确定配体对一系列受体的作用的方法。受体与咖啡因的结合能被认为是确定最佳受体配体复合物的依据。通过文献研究确定了7种不同的神经递质,并在当前的研究中予以考虑。使用AutoDock4.0观察人类神经受体与咖啡因的分子相互作用,研究咖啡因对人脑几个生物过程的影响。分子对接方法确定了谷氨酸gluR2受体受到咖啡因毒性的不利影响,从而影响人类神经系统的神经传递过程。
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引用次数: 0
Toxicological Evaluation of <i>Vaisvanara churna</i> an Ayurvedic Formulation Vaisvanara churna&lt;/i&gt;阿育吠陀配方
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-09-20 DOI: 10.18311/ti/2023/v30i3/33491
R. Ilavarasan, R. Arunadevi, Susan Thomas, Shrirang Balkrishna Jamadagani, Sudesh N. Gaidhani, M. Thenmozhi, N. Manikandan
Vaisvanara churna an ayurvedic formulation was screened for its toxicity profile. The study was carried out based on CCRAS Protocols. For the acute oral toxicity study, Group I served as vehicle control, Vaisvanara churna at a single oral dose of 6500 mg/kg b.w., was administered to 5 male and 5 female Swiss albino mice (Group II) and observed for 14 consecutive days for clinical signs, body weight and mortality. For 90 days repeated dose toxicity study eighty animals (40 male and 40 female) were distributed into four groups. Group I served as vehicle control. Groups II, III, and IV were administered with 450, 2250 and 4500 mg/kg b.w., respectively for 90 days orally. During this period, feed intake, body weight, signs of toxicity, haematological and biochemical parameters were recorded at periodical intervals. After 90 days animals were sacrificed for necropsy, vital organs were weighed and preserved for histopathological analysis. In an acute toxicity study, a single dose of Vaisvanara churna at 6500 mg/kg b.w., caused no mortality in animals, suggesting that the median lethal dose is greater than 6500 mg/kg b.w. In 90-day, repeated dose toxicity study, administration of Vaisvanara churna for 90 days, up to 4500 mg/kg b.w., caused no significant changes in body weights or organ weights of rats in the treated groups when compared with the control group. In addition, haematological and biochemical parameters were within the physiological limits. Histopathological analysis revealed no signs of degeneration. These results showed that Vaisvanara churna is apparently safe as indicated therapeutically for long-term administration for chronic ailments.
对缬草和阿育吠陀配方进行了毒性分析。本研究是根据CCRAS协议进行的。急性口服毒性研究,ⅰ组作为对照,ⅱ组给5只雄性和5只雌性瑞士白化小鼠(组)单次口服剂量6500 mg/kg b.w,连续14天观察临床症状、体重和死亡率。80只动物(雄性和雌性各40只)分为4组,进行90天的重复给药毒性研究。第一组作为车辆对照。II组、III组和IV组分别给予450、2250和4500 mg/kg b.w口服90 d。在此期间,定期记录采食量、体重、毒性体征、血液学和生化指标。90天后处死动物进行尸检,称量重要器官并保存以作组织病理学分析。在一项急性毒性研究中,单剂量6500 mg/kg体重的海参没有引起动物死亡,表明中位致死剂量大于6500 mg/kg体重。在90天的重复剂量毒性研究中,给药90天,最高剂量为4500 mg/kg体重,与对照组相比,给药组大鼠的体重或器官重量没有明显变化。血液学和生化指标均在生理范围内。组织病理学分析未见退变迹象。这些结果表明,缬草显然是安全的,作为治疗慢性疾病的长期管理。
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引用次数: 0
Testicular Toxicity following Subacute Exposure of Arsenic and Mancozeb alone and in Combination: Ameliorative Efficacy of Quercetin and Catechin 亚急性砷和代森锰锌单独和联合暴露后的睾丸毒性:槲皮素和儿茶素的改善效果
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-09-20 DOI: 10.18311/ti/2023/v30i3/32276
Rasia Yousuf, Pawan Kumar Verma, Priyanka Sharma, Shilpa Sood, N. K. Pankaj, Sanjay Agarwal
Mancozeb (MZ) is a contact fungicide having low toxicity in non-target species, but its continuous exposure can be harmful. The aim of the present study was to determine the impact of the toxic interaction between MZ and arsenic on the testicular tissue of rats and to compare the amelioration potential of quercetin and catechin against the induced toxicity. Sixty adult rats were randomly allocated into 10 groups with 6 animals in each. A significant (p<0.05) decline in TAS, TTH, SOD, CAT, GPx, GR and TTH and a rise (p<0.05) in MDA and AOPP-were recorded in testicular tissue of MZ-treated rats in comparison to control. Exposure to different doses of arsenic (10, 50, 100 ppb) also produced a dose-dependent effect on these oxidative biomarkers. Arsenic exposure produces potentiating MZ-induced testicular toxicity in Wistar rats. Testicular damage was further corroborated by extremely severe histopathological changes viz., interstitial as well as sub-capsular congestion, oedema aside from degeneration, necrosis and loss of seminiferous tubules and a drastic deterioration in sperm motility in this group. In contrast, administration of toxicants along with quercetin or catechin markedly attenuated the alterations in oxidative as well as cellular damage biomarkers and testicular histopathological alterations. Our results suggested that simultaneous low dose exposure to arsenic potentiated testicular toxicity induced by MZ. Furthermore, catechin was more potent as compared to quercetin in ameliorating testicular changes induced by concurrent arsenic and MZ exposure.
代森锰锌(MZ)是一种接触性杀菌剂,对非目标物种的毒性较低,但持续暴露可能有害。本研究的目的是确定MZ与砷的毒性相互作用对大鼠睾丸组织的影响,并比较槲皮素和儿茶素对诱导毒性的改善潜力。将60只成年大鼠随机分为10组,每组6只。mz处理大鼠睾丸组织中TAS、TTH、SOD、CAT、GPx、GR、TTH较对照组显著下降(p < 0.05), MDA、aopp升高(p < 0.05)。暴露于不同剂量的砷(10、50、100 ppb)也对这些氧化生物标志物产生剂量依赖效应。砷暴露产生增强mz诱导Wistar大鼠睾丸毒性。极严重的组织病理学改变进一步证实了睾丸损伤,即除了变性、坏死和精管丧失外,还有间质和包膜下充血、水肿以及精子活力的急剧下降。相比之下,与槲皮素或儿茶素一起施用毒物可显著减轻氧化和细胞损伤生物标志物以及睾丸组织病理学改变的改变。我们的研究结果表明,同时低剂量暴露于砷会增强MZ引起的睾丸毒性。此外,与槲皮素相比,儿茶素在改善砷和MZ同时暴露引起的睾丸变化方面更有效。
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引用次数: 0
A 28-Day Repeated Dose Toxicity Evaluation of Creatinine Monohydrate and β-Hydroxy β-Methyl Butyrate Combination in Rodent Model 一水肌酸酐与β-羟基β-丁酸甲酯联合用药28天鼠模型重复剂量毒性评价
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-23 DOI: 10.18311/ti/2023/v30i2/32418
Shivaramakrishnan Balasubramanian, Kavitha Giridharan, K. Kavya, V. Vellaipandi, Gurumurthy Balasubramanian
Substance abuse is a global concern, having a significant influence on society, healthcare, and the economy. Athletes are increasingly using substances to improve their performance or to cope with stress. Therefore, having a thorough awareness of the often misused substances, their effects, and potential toxicities is essential. One such chemical is the mixture of Creatinine Monohydrate (CM) and -Hydroxy Methyl Butyrate (HMB), which is widely used by athletes to increase strength and performance. According to studies, the combination can boost athletic performance, build muscle, and offer several health advantages. To determine the chemicals’ long-term impacts on human health, more research is required because their safety and toxicity are not well-established. Using TOPKAT(Computer-Aided Toxicity Prediction) and Discovery Studio Version 4.0, this study examined the toxicity and pharmacokinetic profiles of CM and HMB. The interaction of HMB and CM may significantly reduce cell viability compared to either drug alone. There were no negative effects seen in the animal models used for the acute oral toxicity study, but additional research is needed to confirm these results and determine the compounds’ long-term safety for human use. The study also performed cytotoxicity studies of individual substances and combinations on VERO and HEP-G2 cell lines and a 28-day repeated dose toxicity study in Wistar albino rats. The study results provide valuable information for healthcare professionals to understand the physiological complications of exposure to such drugs. Overall, the article emphasizes the importance of understanding the potential toxicity of chemical compounds, particularly those used as nutritional supplements.
药物滥用是一个全球性问题,对社会、医疗保健和经济都有重大影响。运动员越来越多地使用物质来提高成绩或应对压力。因此,对经常被滥用的物质、其影响和潜在毒性有一个彻底的认识是至关重要的。其中一种化学物质是肌酸酐一水合物(CM)和羟基丁酸甲酯(HMB)的混合物,运动员广泛使用它来提高力量和表现。根据研究,这种组合可以提高运动成绩,增强肌肉,并提供多种健康优势。为了确定这些化学品对人类健康的长期影响,需要进行更多的研究,因为它们的安全性和毒性还不明确。使用TOPKAT(计算机辅助毒性预测)和Discovery Studio 4.0版,本研究检查了CM和HMB的毒性和药代动力学特征。与单独使用任一药物相比,HMB和CM的相互作用可能显著降低细胞活力。在用于急性口服毒性研究的动物模型中没有发现负面影响,但还需要进一步的研究来证实这些结果,并确定这些化合物对人类使用的长期安全性。该研究还对VERO和HEP-G2细胞系上的单个物质和组合进行了细胞毒性研究,并对Wistar白化大鼠进行了28天的重复剂量毒性研究。研究结果为医疗保健专业人员了解接触此类药物的生理并发症提供了有价值的信息。总的来说,这篇文章强调了了解化合物的潜在毒性的重要性,特别是那些用作营养补充剂的化合物。
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引用次数: 0
Basic Violet-1 Dye Induced Variation in Antioxidative Enzymes Leads to Neurotoxicity in Labeo rohita 碱性Violet-1染料诱导的抗氧化酶变异导致罗氏沼虾神经毒性
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-23 DOI: 10.18311/ti/2023/v30i2/31433
Rajbir Kaur, Arvinder Kaur, Satinder Kaur
The present study explored the potential use of brain anti-oxidative enzymes as pollution biomarkers in fish Labeo rohita. Experiments were conducted to see the neurotoxic effects of dye Basic violet-1 on fish brain enzymes such as lactate dehydrogenase, alkaline phosphatase and acid phosphatase. Acute toxicity tests were performed for 96 hrs with dye concentrations of 0.2 (LC20), 0.4 (LC40), 0.6 (LC60), 0.8 (LC80) and 1 (LC100) mg/l to study biochemical changes. Behavioural observations were also recorded. Recovery experiments were run for 15 and 30 days. Exposure to the dye adversely affects the brain of the fish as evidenced by altered swimming behavior. Significant dose and duration-dependent increase in enzyme activity was recorded for alkaline phosphatase and acid phosphatase while lactate dehydrogenase activity showed a decrease when compared to the control. Lactate dehydrogenase was found to be a maximally affected enzyme as the percentage change over control is 301.26%. The results indicate prolonged neurotoxic effects of the dye as indicated by the altered swimming behaviour and enzymatic profile of fish. The present study recommends the use of L. rohita as sentinel species in water quality studies and supports the incorporation of fish biochemical profiles as a biomarker in water/ wastewater monitoring programs.
本研究探讨了大脑抗氧化酶作为鱼类污染生物标志物的潜在用途。实验观察了染料碱性紫-1对鱼脑酶如乳酸脱氢酶、碱性磷酸酶和酸性磷酸酶的神经毒性作用。用0.2(LC20)、0.4(LC40)、0.6(LC60)、0.8(LC80)和1(LC100)mg/l的染料浓度进行96小时的急性毒性试验,以研究生物化学变化。还记录了行为观察结果。回收实验进行了15天和30天。暴露于染料会对鱼类的大脑产生不利影响,游泳行为的改变就是明证。与对照组相比,碱性磷酸酶和酸性磷酸酶的酶活性记录到显著的剂量和持续时间依赖性增加,而乳酸脱氢酶活性显示出下降。乳酸脱氢酶被发现是受影响最大的酶,与对照相比,其百分比变化为301.26%。结果表明,该染料的神经毒性作用延长,这表明鱼类的游泳行为和酶谱发生了变化。本研究建议在水质研究中使用L.rohita作为哨点物种,并支持将鱼类生物化学特征作为生物标志物纳入水/废水监测计划。
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引用次数: 0
Safety Evaluation of Arsenicum Album in Acute and Sub-Acute Toxicity Studies in Rats 砷剂在大鼠急性和亚急性毒性研究中的安全性评价
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-23 DOI: 10.18311/ti/2023/v30i2/32299
Roshan Lal, M. Sharma, S. Behera, R. K. Regar, Deepika Tripathi, G. N. Kumar, Satvinder Singh, D. Verma, Pankaj Gupta, S. Kaushik, A. Khurana
Arsenic album is frequently prescribed in homoeopathy for many diseases. However, its safety data is not available. Thus, the study’s purpose is to evaluate the oral toxicity of Arsenic album 6C, 30C, and 200C in rats. Arsenic album (6C, 30C, and 200C) was given at 2000 μl/kg for acute toxicity and observed for up to 14 days. For subacute toxicity, it was given for 28 days and observed for clinical signs, change in body weight and Mortality. Hematological, biochemical, organ weight and histopathological analyses were assessed. Results indicate no mortality of arsenic album in acute toxicity and LD50 is >2000 μl/kg. In the subacute toxicity study, arsenic album (200 μl/kg) did not show any significant changes in above parameters. It may be concluded that the arsenic album (6C, 30C, and 200C) is safe and produces no toxicity when administered orally for a prolonged duration at 200 μl/kg in rats.
砷相册经常被用于治疗许多疾病的顺势疗法。然而,其安全数据不可用。因此,本研究的目的是评估砷专辑6C、30C和200C对大鼠的口服毒性。砷相册(6C、30C和200C)的急性毒性剂量为2000μl/kg,观察时间长达14天。对于亚急性毒性,给药28天,观察临床症状、体重变化和死亡率。评估血液学、生化、器官重量和组织病理学分析。结果表明,砷相册急性毒性无死亡,LD50>2000μl/kg。在亚急性毒性研究中,砷相册(200μl/kg)在上述参数中没有显示出任何显著变化。可以得出结论,在大鼠中以200μl/kg的剂量长期口服砷相册(6C、30C和200C)是安全的,并且不会产生毒性。
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引用次数: 1
Toxicity Studies of Trayodashang guggulu, A Classical Ayurvedic Formulation in Experimental Animals 阿育吠陀经典配方三七上谷谷露对实验动物的毒性研究
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-19 DOI: 10.18311/ti/2023/v30i2/30617
M. Bora, Barnali Sinha, M. Gautam, S. Gaidhani, S. Upadhyay, S. Jamadagni, A. Dixit
The present study was undertaken to evaluate the Maximum Tolerated Dose and No Observed Adverse Effect Level of Trayodashang guggulu (TG), an Ayurvedic classical formulation, in Wistar rats. TG was administered orally to Wistar rats in as single dose (2000 mg/kg body weight) in an acute toxicity study. Ninety days repeated dose oral toxicity (subchronic) study was carried out by using three dose levels (250, 500 and 1000 mg/kg body weight) administered orally daily for 90 consecutive days and derived from 28 days dose range-finding study. In acute and subchronic toxicity studies, animals were observed for general clinical signs, mortality, weekly body weight changes, weekly feed intake, weekly water intake, blood biochemical investigation, haematological parameters, and gross pathological and histological investigations. In an acute toxicity study, the dose level of 2000 mg/kg of TG was found to be safe when given at a single dose. In the dose rangefinding study and subchronic toxicity study TG was found to be safe at all tested dose levels. No significant changes in food and water consumption, haematological and blood biochemical parameters were noticed at any dose level in both studies. No major changes were noticed during histopathological evaluation in ninety days repeated dose oral toxicity study. The study concluded that the Maximum Tolerated Dose of TG was found at 2000 mg/kg body weight and the No Observed Adverse Effect Level was found at 1000 mg/kg in Wistar rats.
本研究旨在评估阿育吠陀经典配方Trayodashang guggulu(TG)在Wistar大鼠中的最大耐受剂量和无不良反应水平。在急性毒性研究中,将TG以单剂量(2000mg/kg体重)口服给Wistar大鼠。通过使用连续90天每天口服的三个剂量水平(250、500和1000 mg/kg体重)进行90天重复剂量口服毒性(亚慢性)研究,该研究来源于28天的剂量范围发现研究。在急性和亚慢性毒性研究中,观察动物的一般临床症状、死亡率、每周体重变化、每周采食量、每周饮水量、血液生化调查、血液学参数以及大体病理学和组织学调查。在一项急性毒性研究中,发现单次给药时,剂量水平为2000 mg/kg的TG是安全的。在剂量范围研究和亚慢性毒性研究中,发现TG在所有测试剂量水平下都是安全的。在这两项研究中,在任何剂量水平下,食物和水的消耗、血液学和血液生化参数都没有显著变化。在90天的重复剂量口服毒性研究中,在组织病理学评估期间未发现重大变化。该研究得出结论,在Wistar大鼠中,TG的最大耐受剂量为2000 mg/kg体重,而无观察到的不良反应水平为1000 mg/kg。
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引用次数: 0
Therapeutic Protection of Arsenic-Induced Oxidative Stress and Hepato-Nephro Toxicity by Syzygium cumini (Seed) Ethanolic Extract (SCEE) in Charles Foster Rats 茴香(种子)乙醇提取物(SCEE)对砷诱导大鼠氧化应激和肝肾毒性的保护作用
Q4 Pharmacology, Toxicology and Pharmaceutics Pub Date : 2023-05-19 DOI: 10.18311/ti/2023/v30i2/32429
P. Shankar, Rana Vikram Singh, Arun Kumar
Arsenic (As) is an environmental toxin distributed in groundwater which is presently a global concern. The present study aimed to investigate the efficacy of SCEE in the mitigation of arsenic-induced hepato-renal dysfunction and oxidative stress in rats. Thirty male Charles foster rats (140-160 g) were randomly assigned into three groups. Group I (n = 6) - Control, Group II (n = 6) - SCEE control was administrated with 600 mg kg-1 body weight daily for 60 days and the last Group III (n = 24) was As-treated at 8 mg kg-1 body weight daily for 90 days. Subsequently, Group III was further divided into three subgroups. The subgroup I (n = 6) was immediately sacrificed to observe the arsenic-induced toxicity. Subgroup II (n = 6) was kept on a normal diet for 60 days for auto recovery. Subgroup III (n = 6) was administrated orally by SCEE at 600 mg kg-1 body weight daily for 60 days to decipher the therapeutic potential against arsenic-induced toxicity. The experimental exposure reveals various changes in biochemical parameters of the liver function test and kidney function test in addition to histopathological studies. Chronic exposure to arsenic significantly (p < 0.0001) increased the levels of lipid peroxidation along with significantly reducing the activity of glutathione, superoxide dismutase and catalase. Significant (p < 0.0001) arsenic accumulation was observed in the hepatic-nephron tissues. The dose-dependent SCEE administration against Astoxicity had progressive survival benefits on antioxidant levels, enzymatic activities and histopathological changes. Thus, the study concludes that S.cumini seed has a protective effect against As-induced oxidative stress and hepato-renal intoxication.
砷是一种分布在地下水中的环境毒素,目前已成为全球关注的问题。本研究旨在探讨SCEE对大鼠砷诱导的肝肾功能障碍和氧化应激的影响。雄性Charles foster大鼠30只,体重140 ~ 160 g,随机分为3组。第1组(n = 6)为对照组,第2组(n = 6)为SCEE对照组,每天给予600 mg kg-1体重,连续60 d;第3组(n = 24)为as组,每天给予8 mg kg-1体重,连续90 d。随后,第三组进一步分为三个亚组。第1亚组(n = 6)即刻处死,观察其砷毒性。第二组(n = 6)维持正常饮食60天,自愈。第三组(n = 6)每日口服600 mg kg-1体重的SCEE,持续60天,以了解对砷诱导毒性的治疗潜力。实验暴露除了组织病理学研究外,还揭示了肝功能检查和肾功能检查生化参数的各种变化。慢性砷暴露显著(p < 0.0001)增加了脂质过氧化水平,同时显著降低了谷胱甘肽、超氧化物歧化酶和过氧化氢酶的活性。肝-肾单位组织中砷积累显著(p < 0.0001)。剂量依赖的SCEE给药对抗氧化水平、酶活性和组织病理学变化具有渐进式的生存益处。由此可见,小茴香籽对砷诱导的氧化应激和肝肾中毒具有保护作用。
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引用次数: 1
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Toxicology International
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