Department of Pathology, Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik, Turkey.
Biochem Biophys Res Commun. 2024 Sep 17;725:150258. doi: 10.1016/j.bbrc.2024.150258. Epub 2024 Jun 11.
OBJECTIVE: Long-term exposure to arsenic has been linked to several illnesses, including hypertension, diabetes, hepatic and renal diseases and cardiovascular malfunction. The aim of the current investigation was to determine whether zingerone (ZN) could shield rats against the hepatotoxicity that sodium arsenite (SA) causes. METHODS: The following five groups of thirty-five male Sprague Dawley rats were created: I) Control; received normal saline, II) ZN; received ZN, III) SA; received SA, IV) SA + ZN 25; received 10 mg/kg body weight SA + 25 mg/kg body weight ZN, and V) SA + ZN 50; received 10 mg/kg body weight SA + 50 mg/kg body weight ZN. The experiment lasted 14 days, and the rats were sacrificed on the 15th day. While oxidative stress parameters were studied by spectrophotometric method, apoptosis, inflammation and endoplasmic reticulum stress parameters were measured by RT-PCR method. RESULTS: The SA disrupted the histological architecture and integrity of the liver and enhanced oxidative damage by lowering antioxidant enzyme activity, such as those of glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) level and increasing malondialdehyde (MDA) level in the liver tissue. Additionally, SA increased the mRNA transcript levels of Bcl2 associated x (Bax), caspases (-3, -6, -9), apoptotic protease-activating factor 1 (Apaf-1), p53, tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), c-Jun NH2-terminal kinase (JNK), mitogen-activated protein kinase 14 (MAPK14), MAPK15, receptor for advanced glycation endproducts (RAGE) and nod-like receptor family pyrin domain-containing 3 (NLRP3) in the liver tissue. Also produced endoplasmic reticulum stress by raising the mRNA transcript levels of activating transcription factor 6 (ATF-6), protein kinase RNA-like ER kinase (PERK), inositol-requiring enzyme 1 (IRE1), and glucose-regulated protein 78 (GRP-78). These factors together led to inflammation, apoptosis, and endoplasmic reticulum stress. On the other hand, liver tissue treated with ZN at doses of 25 and 50 mg/kg showed significant improvement in oxidative stress, inflammation, apoptosis and endoplasmic reticulum stress. CONCLUSIONS: Overall, the study's data suggest that administering ZN may be able to lessen the liver damage caused by SA toxicity.
目的：长期接触砷已与多种疾病有关，包括高血压、糖尿病、肝和肾疾病以及心血管功能障碍。本研究的目的是确定是否丁香酚（ZN）可以保护大鼠免受亚砷酸钠（SA）引起的肝毒性。
方法：创建以下五组 35 只雄性 Sprague Dawley 大鼠：I）对照组；给予生理盐水，II）ZN 组；给予 ZN，III）SA 组；给予 SA，IV）SA+ZN 25 组；给予 10mg/kg 体重 SA + 25mg/kg 体重 ZN，V）SA+ZN 50 组；给予 10mg/kg 体重 SA + 50mg/kg 体重 ZN。实验持续 14 天，第 15 天处死大鼠。通过分光光度法研究氧化应激参数，通过 RT-PCR 法测量细胞凋亡、炎症和内质网应激参数。
结果：SA 破坏了肝脏的组织学结构和完整性，并通过降低抗氧化酶活性（如谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、谷胱甘肽（GSH）水平和增加丙二醛（MDA）水平）来增强氧化损伤肝脏组织。此外，SA 增加了 Bcl2 相关 X（Bax）、半胱天冬酶（-3、-6、-9）、凋亡蛋白酶激活因子 1（Apaf-1）、p53、肿瘤坏死因子-α（TNF-α）、核因子 kappa B（NF-κB）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、c-Jun NH2-末端激酶（JNK）、丝裂原激活蛋白激酶 14（MAPK14）、MAPK15、晚期糖基化终产物受体（RAGE）和核苷酸结合寡聚结构域样受体家族含pyrin 结构域 3（NLRP3）在肝组织中的 mRNA 转录水平。它还通过提高活化转录因子 6（ATF-6）、蛋白激酶 RNA 样内质网激酶（PERK）、肌醇需求酶 1（IRE1）和葡萄糖调节蛋白 78（GRP-78）的 mRNA 转录水平引起内质网应激。这些因素共同导致炎症、细胞凋亡和内质网应激。另一方面，用 25 和 50mg/kg 体重的 ZN 处理的肝组织在氧化应激、炎症、细胞凋亡和内质网应激方面有显著改善。
结论：总的来说，研究数据表明，给予 ZN 可能能够减轻 SA 毒性引起的肝损伤。
Biol Trace Elem Res. 2018-7-31
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