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Nrf2与NF-қB在他莫昔芬诱导的肝毒性中的相互作用:西地那非和低剂量γ辐射的一种有前景的治疗方法。

Nrf2 and NF-қB interplay in tamoxifen-induced hepatic toxicity: A promising therapeutic approach of sildenafil and low-dose γ radiation.

作者信息

Karam Heba M, Galal Shereen M, Lotfy Dina M

机构信息

Drug Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.

Health Radiation Research Department, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.

出版信息

Environ Toxicol. 2023 May;38(5):990-996. doi: 10.1002/tox.23742. Epub 2023 Jan 30.

DOI:10.1002/tox.23742
PMID:36715126
Abstract

Tamoxifen-induced hepatotoxicity is an inevitable side effect during breast cancer treatment. Low-dose gamma irradiation (IRR) shows many beneficial effects by stimulating various biological processes. This study evaluates the possible effect of sildenafil and low-dose gamma radiation on liver damages as new treatment strategies. Group I (control), group II: (tamoxifen), group III: (tamoxifen + Sildenafil), group IV: (tamoxifen+ irradiation) and group V: (tamoxifen +Sildenafil + irradiation). Rats were sacrificed after 5 h from tamoxifen injection. Results showed that tamoxifen caused elevation in serum AST, ALT and ALP as well hepatic ROS, iNOS, MDA, Keap-1 and NF-Kb, in addition to diminution in hepatic Nrf2 and HO-1. Exposure to low-dose gamma radiation and sildenafil amended the alterations in the measured parameters in serum and tissue. Moreover, all results were confirmed by histopathological examination. In conclusion, sildenafil and low-dose gamma radiation can mitigate the toxicity induced by tamoxifen in liver tissues. Hence, this treatment could be further evaluated as a new approach for alleviating various liver disorders.

摘要

他莫昔芬诱导的肝毒性是乳腺癌治疗过程中不可避免的副作用。低剂量伽马辐射通过刺激各种生物学过程显示出许多有益作用。本研究评估西地那非和低剂量伽马辐射作为新的治疗策略对肝损伤的可能影响。第一组(对照组),第二组:(他莫昔芬组),第三组:(他莫昔芬+西地那非组),第四组:(他莫昔芬+辐射组)和第五组:(他莫昔芬+西地那非+辐射组)。在注射他莫昔芬5小时后处死大鼠。结果显示,他莫昔芬导致血清AST、ALT和ALP以及肝脏ROS、iNOS、MDA、Keap-1和NF-Kb升高,此外肝脏Nrf2和HO-1减少。暴露于低剂量伽马辐射和西地那非改善了血清和组织中测量参数的变化。此外,所有结果均经组织病理学检查证实。总之,西地那非和低剂量伽马辐射可以减轻他莫昔芬诱导的肝脏组织毒性。因此,这种治疗方法可作为缓解各种肝脏疾病的新方法进行进一步评估。

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引用本文的文献

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Pioglitazone attenuates tamoxifen-induced liver damage in rats via modulating Keap1/Nrf2/HO-1 and SIRT1/Notch1 signaling pathways: In-vivo investigations, and molecular docking analysis.吡格列酮通过调节 Keap1/Nrf2/HO-1 和 SIRT1/Notch1 信号通路减轻他莫昔芬诱导的大鼠肝损伤:体内研究和分子对接分析。
Mol Biol Rep. 2023 Dec;50(12):10219-10233. doi: 10.1007/s11033-023-08847-x. Epub 2023 Nov 7.