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波斯骆驼蓬提取物通过调节氧化应激、炎症和细胞凋亡来减轻环磷酰胺诱导的大鼠肝肾功能损伤。

Salvadora persica extract attenuates cyclophosphamide-induced hepatorenal damage by modulating oxidative stress, inflammation and apoptosis in rats.

机构信息

Department of Immunology and Hematology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia.

Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 7607, Saudi Arabia.

出版信息

J Integr Med. 2022 Jul;20(4):348-354. doi: 10.1016/j.joim.2022.05.001. Epub 2022 May 5.

DOI:10.1016/j.joim.2022.05.001
PMID:35643766
Abstract

OBJECTIVE

Salvadora persica (SP) is used as a food additive and is a common ingredient in folk medicine. This study investigates the antioxidant, anti-inflammatory, and beneficial effects of SP against cyclophosphamide (CYP) toxicity in rats.

METHODS

In a 10-day study, 32 male rats were equally allocated into 4 groups (8 rats/group) as follows: the normal control (NC group), normal rats that only received oral aqueous extract of SP (100 mg/[kg·d]; SP group), animals treated with intraperitoneal CYP injections (30 mg/[kg·d]; CYP group), and the CYP + SP group that concurrently received CYP with SP aqueous extract. Serum samples were collected to measure the liver and renal biochemical profiles, as well as antioxidant and oxidative stress markers and the concentrations of interleukin-1β (IL-1β), IL-6, IL-10, tumor necrosis factor-α (TNF-α), nuclear factor-κB (NF-κB) and adenosine 5'-monophosphate-activated protein kinase (AMPK). Hepatic and renal tissues were also harvested for histopathology and to measure apoptosis using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique, alongside tissue levels of oxidative stress markers.

RESULTS

Liver enzymes, total bilirubin, creatinine and urea, as well as serum IL-1β, IL-6, TNF-α and NF-κB increased significantly, whilst total protein, albumin, calcium, IL-10 and AMPK declined in serum of the CYP group relative to the NC group. The hepatorenal concentrations of glutathione, glutathione peroxidase and catalase declined markedly in the CYP group, whereas malondialdehyde, protein adducts, and apoptosis index increased compared with the NC group. By contrast, the hepatorenal biochemistry and apoptosis index of the SP group were comparable to the NC group. Interestingly, the CYP + SP group had significant improvements in the liver and renal biochemical parameters, enhanced anti-oxidative and anti-inflammatory effects, and marked declines in hepatic and renal apoptosis relative to the CYP group. Moreover, all monitored parameters were statistically indistinguishable between the CYP + SP group and the NC group.

CONCLUSION

This study suggests that the aqueous extract of SP could be a potential remedy against CYP-induced hepatorenal damage and may act by modulating the AMPK/NF-κB signaling pathway and promoting anti-oxidative and anti-inflammatory activities.

摘要

目的

菝葜(SP)被用作食品添加剂,也是民间医学中的常见成分。本研究旨在探讨 SP 对环磷酰胺(CYP)诱导的大鼠毒性的抗氧化、抗炎和有益作用。

方法

在为期 10 天的研究中,将 32 只雄性大鼠等分为 4 组(每组 8 只):正常对照组(NC 组)、仅接受 SP 口服水提物(100mg/[kg·d];SP 组)的正常大鼠、接受腹腔内 CYP 注射的动物(30mg/[kg·d];CYP 组)以及同时接受 CYP 和 SP 水提物的 CYP+SP 组。收集血清样本以测量肝肾功能生化指标以及抗氧化和氧化应激标志物,白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)和腺苷 5'-单磷酸激活蛋白激酶(AMPK)的浓度。还采集肝和肾组织,采用末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记技术测量细胞凋亡,并测量氧化应激标志物的组织水平。

结果

与 NC 组相比,CYP 组的血清中肝酶、总胆红素、肌酐和尿素以及血清 IL-1β、IL-6、TNF-α和 NF-κB 显著升高,而总蛋白、白蛋白、钙、IL-10 和 AMPK 下降。CYP 组肝肾功能的谷胱甘肽、谷胱甘肽过氧化物酶和过氧化氢酶浓度显著降低,而丙二醛、蛋白质加合物和细胞凋亡指数与 NC 组相比增加。相比之下,SP 组的肝肾功能生化指标与 NC 组相当。有趣的是,与 CYP 组相比,CYP+SP 组的肝肾功能生化参数显著改善,抗氧化和抗炎作用增强,肝肾功能凋亡明显下降。此外,与 CYP 组相比,CYP+SP 组与 NC 组的所有监测参数均无统计学差异。

结论

本研究表明,菝葜水提物可能是一种潜在的治疗 CYP 诱导的肝肾功能损伤的方法,可能通过调节 AMPK/NF-κB 信号通路和促进抗氧化和抗炎活性来发挥作用。

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