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乳香黄连木叶水提取物对奥沙利铂诱导的体外和体内肝损伤、氧化应激及DNA损伤的改善作用

Ameliorative effect of aqueous leaf extract of Pistacia lentiscus L. against oxaliplatin-induced hepatic injury, oxidative stress, and DNA damage in vitro and in vivo.

作者信息

Chouikh Nesrine, Benguedouar Lamia, Chaabani Hanen, Abid Essefi Salwa, Haouas Zohra, Mehdi Meriem, Safta Skhiri Sihem, Sifour Mohamed

机构信息

Laboratory of Molecular Toxicology, Faculty of Nature and Life Sciences, University of Jijel, 18000, Jijel, Algeria.

Laboratory of Research On Biologically Compatible Compounds, LR01SE17 University of Monastir, Faculty of Dental Medicine, 5019, Monastir, Tunisia.

出版信息

Med Oncol. 2025 Jan 22;42(2):54. doi: 10.1007/s12032-025-02599-3.

DOI:10.1007/s12032-025-02599-3
PMID:39843633
Abstract

The current study aimed to assess the preventive effects of aqueous leaf extract of Pistacia lentiscus (ALEPL) against Oxaliplatin (OXA)-induced DNA damage, hepatic injury, and oxidative stress. The in vitro cytotoxic and genotoxic effects of OXA and ALEPL on HCT116 colon cancer cells were evaluated using the MTT (Tetrazolium salt reduction) assay and comet assay. The in vivo study involved 24 female NMRI (Naval Medical Research Institute) mice that were equally divided into four groups as follows: Control group, ALEPL-treated group (100 mg/kg), OXA-treated group (7 mg/kg), and ALEPL-treated group (100mg/kg) + OXA (7mg/kg). All animals were sacrificed 48 h after OXA treatment. Samples of liver and blood were collected for histopathological, micronucleus, and biochemical analyses. Oxidative stress parameters were also evaluated through non-enzymatic and enzymatic antioxidant activities. Our findings demonstrated that ALEPL contains high phenolic compounds. In the MTT assay, OXA exerted the most potent cytotoxic effect, but ALEPL alone showed no toxic effect in HCT116 cells. Furthermore, OXA administration caused significant DNA fragmentation both in vitro and in vivo, elevated serum biochemical parameters, and confirmed acute liver damage through histopathological observations compared to the control group. OXA exposure also led to a decrease in hepatic glutathione (GSH) and an increase in lipid peroxidation and antioxidant enzyme activities. From the results of our study, ALEPL pretreatment significantly restored the hepatic toxicity and DNA damage as well as the oxidative stress profile induced by OXA.

摘要

本研究旨在评估乳香黄连木水叶提取物(ALEPL)对奥沙利铂(OXA)诱导的DNA损伤、肝损伤和氧化应激的预防作用。使用MTT(四唑盐还原)试验和彗星试验评估了OXA和ALEPL对HCT116结肠癌细胞的体外细胞毒性和遗传毒性作用。体内研究涉及24只雌性NMRI(海军医学研究所)小鼠,将其平均分为四组,如下:对照组、ALEPL处理组(100 mg/kg)、OXA处理组(7 mg/kg)和ALEPL处理组(100mg/kg)+OXA(7mg/kg)。在OXA处理后48小时处死所有动物。收集肝脏和血液样本进行组织病理学、微核和生化分析。还通过非酶和酶抗氧化活性评估氧化应激参数。我们的研究结果表明,ALEPL含有高酚类化合物。在MTT试验中,OXA表现出最强的细胞毒性作用,但单独的ALEPL在HCT116细胞中未显示出毒性作用。此外,与对照组相比,OXA给药在体外和体内均导致显著的DNA片段化,血清生化参数升高,并通过组织病理学观察证实急性肝损伤。OXA暴露还导致肝脏谷胱甘肽(GSH)减少,脂质过氧化和抗氧化酶活性增加。从我们的研究结果来看,ALEPL预处理显著恢复了由OXA诱导的肝毒性、DNA损伤以及氧化应激状态。

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本文引用的文献

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