合成吡啶酮类似物对白化大鼠的急性和亚急性毒性:基本参数分析。

IF 2.7 4区 医学 Q3 TOXICOLOGY
Vaishali Singh, Lalhruaizela, Ranjeet Maurya, Ved Prakash Singh, Rajesh Kumar Kharwar
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引用次数: 0

摘要

1,4-二氢吡啶酮及其衍生物具有生物学和药理活性。然而,化合物1[乙基-5-氰基-2-甲基-4-(2-硝基苯基)-6-氧-1,4,5,6-四氢吡啶-3-羧酸盐]、化合物2[乙基-4-氯苯基)-5-氰基-2-甲基-6-氧-1,6-二氢吡啶-3-羧酸盐]和化合物3[乙基-5-氰基-2-甲基-6-氧-4-苯基-1,6-二氢吡啶-3-羧酸盐]的毒性、生物学和药理学潜力尚无相关资料。我们评估了化合物1、2和3的急性和亚急性毒性。为了达到提出的目的,大鼠口服不同剂量的1、2和3。急性口服毒性动物分别给予10、20、50和100 mg/100 g bw单次口服剂量,亚急性口服毒性动物分别给予1和10 mg/100 g bw口服剂量,连续28天。常见的生理终点,如食物和水的消耗,粪便重量和死亡率被观察到14和28天。观察体重、食物和水消耗、粪便重量、血液学、生化、器官重量和组织病理学的变化。在急性研究中,给药化合物2导致一只雌性大鼠死亡。然而,没有发现男性的死亡率。雄性和雌性大鼠均有正常的生理终点。在急性和亚急性剂量治疗后,没有注意到任何参数的显著变化。口服化合物1和化合物3后,各组动物均无明显变化。所有化合物在急性或亚急性剂量下均无毒性。需要进一步的研究来检查化合物的生物学和药理学效率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acute and Subacute Toxicity of Synthetic Pyridone Analogs in Albino Rats: Analysis of Basic Parameters.

1,4-Dihydropyridones and its derivatives possess biological and pharmacological activities. However, at present there is no information regarding toxicity and biological as well as pharmacological potentials of Compound 1 [Ethyl-5-cyano-2-methyl-4-(2-nitrophenyl)-6-oxo-1,4,5,6-tetrahydropyridine-3-carboxylate], Compound 2 [Ethyl 4-(4-chlorophenyl)-5-cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate], and Compound 3 [Ethyl-5-cyano-2-methyl-6-oxo-4-phenyl-1,6-dihydropyridine-3-carboxylate]. We evaluated acute and subacute toxicity of Compounds 1, 2, and 3. To achieve the proposed objective, rats were orally administrated with different doses of 1, 2, and 3. For acute oral toxicity animals were administered single oral dose of 10, 20, 50, and 100 mg/100 g bw and for subacute oral toxicity animals were administered oral dose of 1 and 10 mg/100 g bw for 28 days. Common physiological endpoints such as food and water consumption, stool weight and mortality were observed up to 14 and 28 days. Variation in bw, food and water consumption, stool weight, hematological, biochemical, organ weight, and histopathology was observed. In acute study, administration of Compound 2 lead to the mortality of one female rat. However, no mortality was noted in males. Normal physiological endpoints were noted in males as well as female rats. No significant change was noted in any parameters after treatment with acute and subacute doses. After oral administration of Compound 1 and Compound 3 no significant variation was noted in any groups of the animals. All compounds showed no toxic potential for either acute or subacute dose. Further studies are required to check biological and pharmacological efficiency of the compounds.

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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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