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黄花蒿水提物通过氧化铝纳米颗粒(α 和 γ)动物模型诱导的氧化应激调节,刺激 HO-1/MT-1/Cyp450 信号通路。

The aqueous extract of Artemisia Absinthium L. stimulates HO-1/MT-1/Cyp450 signaling pathway via oxidative stress regulation induced by aluminium oxide nanoparticles (α and γ) animal model.

机构信息

Department of Occupational Health Engineering, School of Health, Tehran University of Medical Sciences, Tehran, Iran.

Department of Occupational Health Engineering, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

BMC Complement Med Ther. 2023 Sep 5;23(1):310. doi: 10.1186/s12906-023-04121-6.

Abstract

BACKGROUND

This research aimed to evaluate the protective effects of Artemisia Absinthium L. (Abs) against liver damage induced by aluminium oxide nanoparticles (AlO NPs) in rats, including both structural and functional changes associated with hepatotoxicity.

METHODS

Thirty-six rats were randomly divided into six groups (n = 6). The first group received no treatment. The second group was orally administered Abs at a dose of 200 mg/kg/b.w. The third and fifth groups were injected intraperitoneally with γ-AlO NPs and α-AlO NPs, respectively, at a dose of 30 mg/kg/b.w. The fourth and sixth groups were pre-treated with oral Abs at a dose of 200 mg/kg/b.w. along with intraperitoneal injection of γ-AlO NPs and α-AlO NPs, respectively, at a dose of 30 mg/kg/b.w.

RESULTS

Treatment with γ-AlO NPs resulted in a significant decrease (P < 0.05) in total body weight gain, relative liver weight to body weight, and liver weight in rats. However, co-administration of γ-AlO NPs with Abs significantly increased body weight gain (P < 0.05). Rats treated with AlO NPs (γ and α) exhibited elevated levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), alanine transaminase (ALT), and aspartate aminotransferase (AST). Conversely, treatment significantly reduced glutathione peroxidase (GPx), catalase (CAT), total superoxide dismutase (T-SOD), and total antioxidant capacity (TAC) levels compared to the control group. Furthermore, the expression of heme oxygenase-1 (HO-1) and metallothionein-1 (MT-1) mRNAs, cytochrome P450 (CYP P450) protein, and histopathological changes were significantly up-regulated in rats injected with AlO NPs. Pre-treatment with Abs significantly reduced MDA, AST, HO-1, and CYP P450 levels in the liver, while increasing GPx and T-SOD levels compared to rats treated with AlO NPs.

CONCLUSION

The results indicate that Abs has potential protective effects against oxidative stress, up-regulation of oxidative-related genes and proteins, and histopathological alterations induced by AlO NPs. Notably, γ-AlO NPs exhibited greater hepatotoxicity than α-AlO NPs.

摘要

背景

本研究旨在评估艾草(Abs)对大鼠氧化亚铝纳米颗粒(AlO NPs)诱导的肝损伤的保护作用,包括与肝毒性相关的结构和功能变化。

方法

36 只大鼠随机分为 6 组(n=6)。第一组不做任何处理。第二组灌胃给予 Abs200mg/kg/b.w。第三组和第五组分别腹腔注射γ-AlO NPs 和α-AlO NPs,剂量为 30mg/kg/b.w。第四组和第六组先灌胃 Abs200mg/kg/b.w.,再分别腹腔注射γ-AlO NPs 和α-AlO NPs,剂量为 30mg/kg/b.w。

结果

γ-AlO NPs 处理组大鼠的总体重增加、相对肝重/体重和肝重显著降低(P<0.05)。然而,γ-AlO NPs 与 Abs 联合给药显著增加了体重增加(P<0.05)。用 AlO NPs(γ 和α)处理的大鼠丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、丙二醛(MDA)、诱导型一氧化氮合酶(iNOS)水平升高。相反,与对照组相比,治疗组谷胱甘肽过氧化物酶(GPx)、过氧化氢酶(CAT)、总超氧化物歧化酶(T-SOD)和总抗氧化能力(TAC)水平显著降低。此外,用 AlO NPs 处理的大鼠血红素加氧酶-1(HO-1)和金属硫蛋白-1(MT-1)mRNA、细胞色素 P450(CYP P450)蛋白和组织病理学变化的表达显著上调。与用 AlO NPs 处理的大鼠相比,Abs 预处理显著降低了肝脏 MDA、AST、HO-1 和 CYP P450 的水平,同时增加了 GPx 和 T-SOD 的水平。

结论

结果表明,Abs 对 AlO NPs 诱导的氧化应激、氧化相关基因和蛋白的上调以及组织病理学改变具有潜在的保护作用。值得注意的是,γ-AlO NPs 比α-AlO NPs 具有更大的肝毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abe1/10478434/13a3fe9e3bac/12906_2023_4121_Fig1_HTML.jpg

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