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选定合成化合物对庆大霉素诱导的肾毒性的肾保护潜力。

The nephroprotective potential of selected synthetic compound against gentamicin induced nephrotoxicity.

机构信息

Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan.

Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.

出版信息

BMC Pharmacol Toxicol. 2024 Sep 27;25(1):68. doi: 10.1186/s40360-024-00765-3.

Abstract

BACKGROUND

Nephrotoxicity, the rapid impairment of kidney function caused by harmful drugs and chemicals, affects about 20% of cases and is projected to become a leading cause of death by reactive oxygen species (ROS). Gentamicin (GM), an aminoglycoside antibiotic is one of the well know drugs/chemicals to cause nephrotoxicity both in humans and animals.

METHODS

A study on the effects of a synthetic phenolic compound, called 5-a, on GM-induced nephrotoxicity in male Wistar albino rats was conducted. The rats were grouped into five groups: normal control (NC), GM control (GM), positive control (GM + Dexa), treatment I (GM + 5-a 5 mg/kg) and treatment II (GM + 5-a 10 mg/kg). Throughout the experiment, the rats' weights were monitored, and at its conclusion, their serum and kidney tissues were analyzed for renal function indicators and inflammatory markers. The study also included histopathological evaluations, molecular docking studies, blood and urine analyses for electrolyte changes, and behavioural assessments for central nervous system impact.

RESULTS

2-{5-[(2-hydroxyethyl)-sulfanyl]-1,3,4-oxadiazol-2-yl} phenol (5-a) significantly protected against renal damage by reducing inflammatory markers, improving antioxidant defences, and decreasing kidney injury, particularly at higher doses. The findings suggest that compound 5-a, due to its anti-inflammatory and antioxidant properties, could be a promising therapeutic option for reducing gentamicin-induced nephrotoxicity and potentially for other kidney disorders in the future.

CONCLUSION

These findings highlight the therapeutic effects of compound 5-a in alleviating gentamicin-induced nephrotoxicity.

摘要

背景

肾毒性是指有害药物和化学物质引起的肾功能迅速损害,约影响 20%的病例,预计将成为活性氧(ROS)引起的主要死亡原因。庆大霉素(GM)是一种氨基糖苷类抗生素,是导致人类和动物肾毒性的知名药物/化学物质之一。

方法

本研究旨在探讨一种名为 5-a 的合成酚类化合物对雄性 Wistar 白化大鼠 GM 诱导的肾毒性的影响。将大鼠分为五组:正常对照组(NC)、GM 对照组(GM)、阳性对照组(GM+地塞米松)、治疗 I 组(GM+5-a 5mg/kg)和治疗 II 组(GM+5-a 10mg/kg)。在整个实验过程中,监测大鼠的体重,实验结束时,分析其血清和肾脏组织的肾功能指标和炎症标志物。该研究还包括组织病理学评估、分子对接研究、血液和尿液分析电解质变化以及中枢神经系统影响的行为评估。

结果

2-{5-[(2-羟乙基)-硫基]-1,3,4-恶二唑-2-基}苯酚(5-a)通过降低炎症标志物、改善抗氧化防御和减少肾损伤显著保护肾脏免受损伤,特别是在高剂量下。研究结果表明,由于其抗炎和抗氧化特性,化合物 5-a 可能是一种有前途的治疗选择,可用于减轻庆大霉素诱导的肾毒性,并可能在未来用于其他肾脏疾病。

结论

这些发现强调了化合物 5-a 缓解庆大霉素诱导的肾毒性的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8af/11438099/c00b5eda9761/40360_2024_765_Fig1_HTML.jpg

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