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阿魏酸乙酯部位通过调节脑乙酰胆碱酯酶活性、DNA 损伤和促炎细胞因子逆转顺铂诱导的神经毒性。

Reversal of cisplatin triggered neurotoxicity by Acacia hydaspica ethyl acetate fraction via regulating brain acetylcholinesterase activity, DNA damage, and pro-inflammatory cytokines in the rodent model.

机构信息

Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.

出版信息

BMC Complement Med Ther. 2022 Jul 5;22(1):179. doi: 10.1186/s12906-022-03657-3.

DOI:10.1186/s12906-022-03657-3
PMID:35790919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9254489/
Abstract

BACKGROUND

Cisplatin (CisPT) is a chemotherapeutic that outcome in adverse effects including neurotoxicity. We examined the efficacy of hydaspica ethyl acetate extract (AHE) against CisPT-prompted neurotoxicity.

METHODS

Group I: Distilled water; Group II: CisPT (12 mg/kg b.w. i.p) on the 13 day of treatment. Group III: received AHE (400 mg/kg b.w) orally for 16 days. Group IV and V received 200 and 400 mg/kg b.w AHE orally for 16 days while CisPT injection on day 13, respectively. Group VI: received Silymarin (100 mg/kg b.w) orally for 16 days and CP (12 mg/kg b.w., i.p.) on day 13. TNF-α, IL6, brain acetylcholinesterase activity (AChE), oxidative trauma markers, genotoxicity, antioxidant enzymes, and morphological alterations in cerebral hemispheres were inspected.

RESULTS

AHE administration before CisPT considerably reduced both tissue TNF-α and IL 6 expressions compared to CisPT treated group in a dose-dependent manner. AHE treatment (400 mg/kg b.w) significantly ameliorated brain AChE activity. Brain tissue MDA, HO and NO content were markedly (p < 0.001) elevated after CisPT inoculation while a noticeable (p < 0.001) diminution was observed in AHE treatment groups. AHE treatment significantly (p < 0.001) improved brain antioxidant defense in a dose-dependent manner. Furthermore, AHE efficiently recused CisPT to induce DNA damage in brain tissue as revealed by ladder assay and DNA fragmentation patterns. Histopathological findings revealed severe neurodegenerations in CisPT treated group, however, AHE treatment noticeably precluded morphological alterations and neuron damages induced by CisPT.

CONCLUSION

A. hydaspica AHE extract may be provided as a prospective adjuvant that precludes CisPT-induced neurotoxicity due to its radical scavenging and antioxidant potential.

摘要

背景

顺铂(CisPT)是一种化疗药物,会导致神经毒性等不良反应。我们研究了水飞蓟乙酸乙酯提取物(AHE)对 CisPT 诱发的神经毒性的疗效。

方法

第 I 组:蒸馏水;第 II 组:在第 13 天治疗时腹腔注射 CisPT(12mg/kg 体重)。第 III 组:连续 16 天口服 400mg/kg 体重 AHE。第 IV 组和第 V 组分别连续 16 天口服 200 和 400mg/kg 体重 AHE,同时在第 13 天腹腔注射 CisPT。第 VI 组:连续 16 天口服水飞蓟素(100mg/kg 体重),第 13 天腹腔注射 CP(12mg/kg 体重)。检测 TNF-α、IL6、大脑乙酰胆碱酯酶活性(AChE)、氧化应激标志物、遗传毒性、抗氧化酶和大脑半球的形态改变。

结果

与 CisPT 治疗组相比,AHE 给药可显著降低 TNF-α和 IL6 的组织表达,且呈剂量依赖性。AHE 治疗(400mg/kg 体重)可显著改善大脑 AChE 活性。CisPT 接种后,脑组织 MDA、HO 和 NO 含量明显升高(p<0.001),而 AHE 治疗组则明显降低(p<0.001)。AHE 治疗可显著改善大脑抗氧化防御能力,呈剂量依赖性。此外,AHE 还能有效阻止 CisPT 诱导的脑组织 DNA 损伤,这一点从梯状电泳和 DNA 片段化模式中可以看出。组织病理学检查结果显示 CisPT 治疗组出现严重的神经退行性改变,而 AHE 治疗可明显防止 CisPT 引起的形态改变和神经元损伤。

结论

A. hydaspica AHE 提取物可能作为一种潜在的辅助治疗药物,通过清除自由基和抗氧化作用来预防 CisPT 引起的神经毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/f870246d70c0/12906_2022_3657_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/ae020aa7fad7/12906_2022_3657_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/255b50bd1d2e/12906_2022_3657_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/2eb017640a6e/12906_2022_3657_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/f870246d70c0/12906_2022_3657_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/ae020aa7fad7/12906_2022_3657_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/255b50bd1d2e/12906_2022_3657_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/2eb017640a6e/12906_2022_3657_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71e6/9254489/f870246d70c0/12906_2022_3657_Fig4_HTML.jpg

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