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补骨脂素对环磷酰胺介导的Wistar大鼠肾应激、炎症和纤维化的肾保护作用:NF-κB和TGF-β1信号分子的可能作用

Nephroprotective Effect of Bergapten Against Cyclophosphamide-Mediated Renal Stress, Inflammation, and Fibrosis in Wistar Rats: Probable Role of NF-kB and TGF-β1 Signaling Molecules.

作者信息

Mohsin Nehal, Akhtar Mohammad Shabib, Alkahtani Saad A, Walbi Ismail A, Alhazmi Yasir, Alam Md Niyaz, Bhardwaj Alok

机构信息

Department of Clinical Pharmacy, College of Pharmacy, Najran University, P.O. Box 1988, Najran 1644, Kingdom of Saudi Arabia.

Ram-Esh Institute of Vocational & Technical Education, Greater Noida, Uttar Pradesh 201306, India.

出版信息

ACS Omega. 2024 Apr 12;9(16):18296-18303. doi: 10.1021/acsomega.4c00124. eCollection 2024 Apr 23.

Abstract

Cyclophosphamide (CPM) is a well-established antineoplastic drug with marked clinical outcomes in various types of cancers. Despite being a promising drug, its use is associated with significant renal toxicity and often limits its use, leading to compromised clinical outcomes. Therefore, this study explored the renal protective effect of bergapten (BGP), a natural bioactive compound that showed marked antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. Till now, BGP has not been studied for its renal protective effect in an model. Animals were divided into control, toxic, BGP-3, BGP-10, and BGP . The control group was treated with normal saline for 2 weeks. To the toxic group, CPM 200 mg/kg was given on day 7 as i.p. To BGP-3, 10, and , BGP-3 and 10 mg/kg, ip was given 2 weeks with a single shot of CPM 200 day 7. To the group, only BGP 10 mg/kg, ip was given from day 1 to day 14. After 14 days, animals were sacrificed, and kidneys were removed and studied for the markers of oxidative stress, inflammation, renal injury, renal fibrosis, and renal damage using biochemical, histopathological, and immunohistochemical studies. We found that BGP-10 effectively reversed the damage toward normal, whereas BGP-3 failed to exhibit a significant renal protective effect. We conclude that bergapten could be a potential renal protective drug, and hence, more detailed cellular molecular-based studies are needed to bring this drug from the bench to the bedside.

摘要

环磷酰胺(CPM)是一种成熟的抗肿瘤药物,在各类癌症中具有显著的临床疗效。尽管它是一种有前景的药物,但其使用与显著的肾毒性相关,常常限制了其应用,导致临床疗效受损。因此,本研究探索了补骨脂素(BGP)的肾脏保护作用,补骨脂素是一种天然生物活性化合物,具有显著的抗氧化、抗炎、抗癌和神经保护作用。到目前为止,尚未在[具体动物]模型中研究补骨脂素的肾脏保护作用。将动物分为对照组、毒性组、BGP - 3组、BGP - 10组和BGP组。对照组用生理盐水治疗2周。毒性组在第7天腹腔注射200mg/kg的CPM。BGP - 3组、BGP - 10组和[具体组],在第7天单次注射CPM 200的情况下,连续2周腹腔注射3mg/kg和10mg/kg的BGP。[具体组]从第1天到第14天仅腹腔注射10mg/kg的BGP。14天后,处死动物,取出肾脏,使用生化、组织病理学和免疫组织化学研究方法,对氧化应激、炎症、肾损伤、肾纤维化和肾损伤标志物进行研究。我们发现BGP - 10有效地将损伤逆转至正常状态,而BGP - 3未能表现出显著的肾脏保护作用。我们得出结论,补骨脂素可能是一种潜在的肾脏保护药物,因此,需要进行更详细的基于细胞分子的研究,以便将这种药物从实验室应用到临床。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07c2/11044238/57ceee7c8b82/ao4c00124_0001.jpg

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