Protective effects of cardamom aqueous extract against tamoxifen-induced pancreatic injury in female rats.

IF 1.6 4区 医学 Q4 TOXICOLOGY
Toxicological Research Pub Date : 2023-06-27 eCollection Date: 2023-10-01 DOI:10.1007/s43188-023-00198-w
Hala Attia, Afraa Alzoubi, Nour Al-Anazi, Aliah Alshanwani, Naglaa El-Orabi, Alaa Alanteet, Raeesa Mohamad, Rehab Ali
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引用次数: 0

Abstract

Tamoxifen (TAM) is a commonly used drug for breast cancer treatment. Although effective, TAM has deleterious effects on many organs. The toxic effects of TAM on the pancreas and the underlying mechanisms however, have not fully investigated. In the present study, we investigated the effects of TAM on the pancreatic tissue in female rats. We also examined whether cardamom aqueous extract (CAE) protects against TAM-induced pancreatic injury. TAM-intoxicated rats were injected with 45 mg/kg of TAM for 10 days, whereas rats in the CAE-treated group were administered 10 mL/kg of CAE for 20 days, starting 10 days prior to TAM administration. Treatment with TAM resulted in severe degeneration of the pancreatic acini and marked increases in the serum levels of pancreatic lipase, α-amylase, glucose, fatty acids and triglycerides along with decreased insulin serum levels. TAM led to oxidative stress as evident from a significant increase in the pancreatic levels of lipid peroxides and nitric oxide along with the depletion of reduced glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, inflammation was indicated by a significant increase in tumor necrosis factor-α and interleukin-6 levels, enhanced expression of the macrophage recruitment marker; CD68 as well as up-regulated protein levels of toll-like receptor 4 and nuclear factor kappa B and increased p-p38/MAPK ratio; which are important signals in the production of inflammatory cytokines. TAM also markedly increased the pancreatic levels of caspase-3 and BAX reflecting its apoptotic effects. The CAE treatment ameliorated all the biochemical and histological changes induced by TAM. The present study revealed, for the first time, that TAM has toxic effects on the pancreatic tissue through oxidative stress, inflammation and apoptotic effects. The present study also provides evidence that CAE exerts cytoprotective effects against these deleterious effects induced by TAM in the pancreatic tissue.

Supplementary information: The online version contains supplementary material available at 10.1007/s43188-023-00198-w.

豆蔻水提取物对三苯氧胺诱导的雌性大鼠胰腺损伤的保护作用。
三苯氧胺(TAM)是治疗癌症的常用药物。TAM虽然有效,但对许多器官都有有害影响。然而,TAM对胰腺的毒性作用及其潜在机制尚未得到充分研究。在本研究中,我们研究了TAM对雌性大鼠胰腺组织的影响。我们还检测了豆蔻水提取物(CAE)是否对TAM诱导的胰腺损伤具有保护作用。TAM中毒的大鼠注射45mg/kg的TAM 10天,而CAE治疗组的大鼠从TAM给药前10天开始注射10mL/kg的CAE 20天。TAM治疗导致胰腺腺泡严重变性,胰腺脂肪酶、α-淀粉酶、葡萄糖、脂肪酸和甘油三酯的血清水平显著升高,胰岛素血清水平下降。TAM导致氧化应激,这一点从胰腺脂质过氧化物和一氧化氮水平的显著增加以及还原型谷胱甘肽、谷胱甘肽过氧化物酶和超氧化物歧化酶的耗竭中可以明显看出。此外,炎症表现为肿瘤坏死因子-α和白细胞介素-6水平显著升高,巨噬细胞募集标志物表达增强;CD68以及上调toll样受体4和核因子κB的蛋白水平,并增加p-p38/MAPK比率;其是炎性细胞因子产生中的重要信号。TAM还显著增加了胰腺中胱天蛋白酶-3和BAX的水平,反映了其凋亡作用。CAE治疗改善了TAM引起的所有生化和组织学变化。本研究首次揭示了TAM通过氧化应激、炎症和凋亡作用对胰腺组织具有毒性作用。本研究还提供了证据,证明CAE对TAM在胰腺组织中诱导的这些有害作用具有细胞保护作用。补充信息:在线版本包含补充材料,网址为10.1007/s43188-023-00198-w。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.20
自引率
4.30%
发文量
39
期刊介绍: Toxicological Research is the official journal of the Korean Society of Toxicology. The journal covers all areas of Toxicological Research of chemicals, drugs and environmental agents affecting human and animals, which in turn impact public health. The journal’s mission is to disseminate scientific and technical information on diverse areas of toxicological research. Contributions by toxicologists, molecular biologists, geneticists, biochemists, pharmacologists, clinical researchers and epidemiologists with a global view on public health through toxicological research are welcome. Emphasis will be given to articles providing an understanding of the toxicological mechanisms affecting animal, human and public health. In the case of research articles using natural extracts, detailed information with respect to the origin, extraction method, chemical profiles, and characterization of standard compounds to ensure the reproducible pharmacological activity should be provided.
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