PDF(Pubmed)
Abstract：
Background The nephrotoxic side effects of gentamicin, a potent aminoglycoside antibiotic, significantly restrict its clinical use. Identifying compounds that can mitigate this nephrotoxicity is of paramount importance. The research examines how the ethanolic extract of Carica papaya seeds (EECPS) and isoliquiritigenin (ISL), a flavonoid separated from them, protect the kidneys and fight free radicals in gentamicin-treated Wistar albino rats. Methodology A total of 48 mature Wistar albino rats were divided into eight groups, with each group consisting of six rats. The experimental setup included a normal control group receiving oral saline as a negative control, and a standard control group administered gentamicin intraperitoneally (IP) at 100 mg/kg body weight for 13 days to induce nephrotoxicity, followed by oral silymarin at 100 mg/kg body weight as a positive control from days 14 to 21. A toxicant control group was exposed to gentamicin IP without subsequent treatment. Two test groups were given 400 mg/kg and 800 mg/kg of EECPS orally after being given gentamicin. Three other test groups were given 20 mg/kg, 40 mg/kg, and 80 mg/kg of ISL orally after being given gentamicin. Serum levels of creatinine, urea, and blood urea nitrogen (BUN) were used to test renal function. Malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH), which are signs of oxidative stress, were also measured in renal tissues. Results Gentamicin administration markedly increased serum creatinine, urea, and BUN levels, confirming its nephrotoxic effect. Nephroprotection depended on the dose of EECPS and ISL used. It was found that 80 mg/kg of ISL had the most powerful effect, which was not what was thought at first. These treatments effectively reduced MDA and NO levels while enhancing GSH levels, exhibiting their strong antioxidant properties. Notably, the nephroprotective efficacy of these treatments exceeded that of silymarin, a known nephroprotective agent. Histopathological analysis confirmed reduced renal damage and enhanced tissue repair in the treated groups. Conclusions These findings demonstrate how effective EECPS and ISL are at shielding the kidneys from gentamicin-caused damage. They do this by acting as antioxidants and nephroprotectants. Their ability to protect kidney function and fight oxidative stress makes them interesting as possible treatments for gentamicin-related kidney damage. These results advocate for further investigation into the utility of these natural compounds in the management of nephrotoxicity.
摘要：
背景庆大霉素的肾毒性副作用，一种强效的氨基糖苷类抗生素,严重限制了其临床应用。鉴定可以减轻这种肾毒性的化合物是最重要的。该研究考察了番木瓜种子的乙醇提取物（EECPS）和异甘草素（ISL），从它们中分离出来的类黄酮，在庆大霉素治疗的Wistar白化病大鼠中保护肾脏并抵抗自由基。方法将48只成年Wistar白化病大鼠分为8组,每组6只大鼠。实验设置包括接受口服盐水作为阴性对照的正常对照组，和标准对照组以100mg/kg体重腹膜内（IP）给予庆大霉素13天以诱导肾毒性，然后在第14至21天口服100mg/kg体重的水飞蓟素作为阳性对照。将毒物对照组暴露于庆大霉素IP而不进行后续处理。两个试验组在给予庆大霉素后分别口服400mg/kg和800mg/kg的EECPS。其他三个试验组给予20mg/kg，40mg/kg,给予庆大霉素后口服80mg/kg的ISL。血清肌酐水平,尿素,用血尿素氮(BUN)检测肾功能。丙二醛(MDA),一氧化氮（NO），和还原型谷胱甘肽（GSH），这是氧化应激的迹象，也在肾组织中测量。结果庆大霉素显著升高血清肌酐,尿素,和BUN水平，确认其肾毒性作用。肾保护取决于所使用的EECPS和ISL的剂量。发现80mg/kg的ISL具有最强大的作用，这不是最初的想法。这些治疗有效降低MDA和NO水平，同时提高GSH水平，表现出他们强大的抗氧化性能。值得注意的是,这些治疗的肾保护功效超过了水飞蓟素，一种已知的肾保护剂。组织病理学分析证实，治疗组肾脏损伤减轻，组织修复增强。结论这些发现证明了EECPS和ISL在保护肾脏免受庆大霉素引起的损害方面的有效性。它们通过充当抗氧化剂和肾保护剂来做到这一点。它们保护肾功能和对抗氧化应激的能力使它们成为庆大霉素相关肾损伤的可能治疗方法。这些结果主张进一步研究这些天然化合物在肾毒性管理中的效用。
