The Hepatoprotective Effect of a Newly Synthesized 5-Mercapto-1,2,4-Triazole Derivative based on Nalidixic Acid Against Ccl4 induced Oxidative Stress in Mice

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Ibrahim Mhaidat, lena tahat, Ghada Alomari, Laiali AL-Quraan, Abeer Gharaibeh, Bahaa Al-Trad
{"title":"The Hepatoprotective Effect of a Newly Synthesized 5-Mercapto-1,2,4-Triazole Derivative based on Nalidixic Acid Against Ccl4 induced Oxidative Stress in Mice","authors":"Ibrahim Mhaidat, lena tahat, Ghada Alomari, Laiali AL-Quraan, Abeer Gharaibeh, Bahaa Al-Trad","doi":"10.2174/0115701808294306240613104855","DOIUrl":null,"url":null,"abstract":"Background: Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)-4H-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl4 induced oxidative stress in mice. Materials and Methods: The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1 H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl4 (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl4 at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl4 co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl4 administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). However, pre and post-treatment with the new newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities (p < 0.05). Conclusion: This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl4-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Letters in Drug Design & Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115701808294306240613104855","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Oxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)-4H-1,2,4-triazol-3-yl)-7-methyl-1,8-naphthyridin] (MTTN) 3 compound against CCl4 induced oxidative stress in mice. Materials and Methods: The MTTN compound was synthesized through the interaction and then cyclization of p-tolylisothiocyanate with nalidixic acid hydrazide. By using 1 H-NMR, 13C-NMR, IR, and elemental analyses, the structure of the newly synthesized MTTN compound was identified. To investigate the hepatoprotective effect of this compound, forty BALB/c mice were divided into four groups (n=10) as follows: the control group, the oxidative stress-induced group, which was intraperitoneally injected with 10% CCl4 (2 mL/kg), one pre-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days before being treated with CCl4 at day 8, and one post-treatment group, which was treated orally with 200 mg/kg of MTTN compound for 8 days simultaneously with CCl4 co-administration at days 3 and 5. At day 9, animals were scarified and serum and liver samples were collected. Results: CCl4 administration caused significant hepatotoxicity as evidenced by marked elevation in the serum activity of the liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and high blood cholesterol levels. Furthermore, the hepatic malondialdehyde (MDA) level, a marker of lipid peroxidation, was increased with CCl4 administration that was associated with a decrease in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.05). However, pre and post-treatment with the new newly synthesized MTTN compound significantly reduced the serum levels of AST, ALT, and cholesterol and reduced hepatic oxidative stress as indicated by the decrease in the hepatic MDA level and the increases in the SOD and CAT activities (p < 0.05). Conclusion: This study suggests that the newly synthesized MTTN compound has a potent antioxidant property and can protect against CCl4-induced liver injury. Thus, with more clinical studies, this compound may be used as effective therapeutic agents against oxidative stress related diseases.
基于萘啶酸新合成的 5-巯基-1,2,4-三唑衍生物对 Ccl4 诱导的小鼠氧化应激的肝保护作用
背景:氧化应激在包括糖尿病和癌症在内的多种疾病的发病过程中起着关键作用。最近的研究表明,三唑化合物的衍生物具有很强的抗氧化活性。因此,本研究旨在探讨一种基于萘啶酸新合成的 5-巯基-1,2,4-三唑[1-乙基-3-(5-巯基-4-(对甲苯基)-4H-1,2,4-三唑-3-基)-7-甲基-1,8-萘啶](MTTN)3 化合物对 CCl4 诱导的小鼠氧化应激的保肝作用。材料与方法:对甲苯基异硫氰酸酯与萘啶酸酰肼相互作用并环化合成了 MTTN 化合物。通过 1 H-NMR、13C-NMR、IR 和元素分析,确定了新合成的 MTTN 化合物的结构。为研究该化合物的保肝作用,将 40 只 BALB/c 小鼠分为以下四组(n=10):对照组;氧化应激诱导组,腹腔注射 10% CCl4(2 mL/kg);预处理组,在第 8 天注射 CCl4 之前口服 200 mg/kg MTTN 复合物治疗 8 天;后处理组,在第 3 天和第 5 天注射 CCl4 的同时口服 200 mg/kg MTTN 复合物治疗 8 天。第 9 天,对动物进行去疤处理,并采集血清和肝脏样本。结果给动物注射 CCl4 会引起明显的肝中毒,表现为血清中肝脏酶、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的活性明显升高,以及血液中胆固醇水平升高。此外,肝脏丙二醛(MDA)水平(脂质过氧化的标志)在服用 CCl4 后升高,与肝脏超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的降低有关(p < 0.05)。然而,使用新合成的 MTTN 化合物进行治疗前后,AST、ALT 和胆固醇的血清水平明显降低,肝脏 MDA 水平降低,SOD 和 CAT 活性提高,从而减轻了肝脏氧化应激(p < 0.05)。结论这项研究表明,新合成的 MTTN 化合物具有强大的抗氧化性,可防止 CCl4 引起的肝损伤。因此,随着更多临床研究的开展,这种化合物可能会被用作治疗氧化应激相关疾病的有效药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信