Abstract：
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.
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.
摘要：
目的：长期接触砷与几种疾病有关，包括高血压,糖尿病,肝肾疾病和心血管疾病。当前研究的目的是确定姜酮（ZN）是否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SpragueDawley大鼠：I）对照组；接受生理盐水，II)ZN；收到ZN，III)SA；收到SA，IV)SA+ZN25;接受10mg/kg体重SA+25mg/kg体重ZN,和V)SA+ZN50;接受10mg/kg体重SA+50mg/kg体重ZN。实验持续了14天,在第15天处死大鼠.用分光光度法研究氧化应激参数,凋亡，通过RT-PCR方法测量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来增强氧化损伤，例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）水平和肝脏组织中丙二醛（MDA）水平升高。此外,SA增加了Bcl2相关x（Bax）的mRNA转录水平，caspases(-3,-6,-9),凋亡蛋白酶活化因子1（Apaf-1），p53,肿瘤坏死因子-α(TNF-α),核因子κB(NF-κB),白细胞介素-1β（IL-1β），白细胞介素-6（IL-6），c-JunNH2末端激酶（JNK），丝裂原活化蛋白激酶14（MAPK14），MAPK15，肝组织中的晚期糖基化终产物（RAGE）和节点样受体家族含pyrin结构域3（NLRP3）的受体。还通过提高激活转录因子6（ATF-6）的mRNA转录水平产生内质网应激，蛋白激酶RNA样ER激酶（PERK），需要肌醇的酶1（IRE1），和葡萄糖调节蛋白78（GRP-78）。这些因素共同导致炎症，凋亡，和内质网应激。另一方面,以25和50mg/kg的剂量用ZN处理的肝组织显示出氧化应激的显着改善，炎症,细胞凋亡和内质网应激。
结论：总体而言，研究数据表明，给予ZN可能能够减轻SA毒性引起的肝损伤。
方法：创建以下五组35只雄性SpragueDawley大鼠：I）对照组；接受生理盐水，II)ZN；收到ZN，III)SA；收到SA，IV)SA+ZN25;接受10mg/kg体重SA+25mg/kg体重ZN,和V)SA+ZN50;接受10mg/kg体重SA+50mg/kg体重ZN。实验持续了14天,在第15天处死大鼠.用分光光度法研究氧化应激参数,凋亡，通过RT-PCR方法测量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来增强氧化损伤，例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）水平和肝脏组织中丙二醛（MDA）水平升高。此外,SA增加了Bcl2相关x（Bax）的mRNA转录水平，caspases(-3,-6,-9),凋亡蛋白酶活化因子1（Apaf-1），p53,肿瘤坏死因子-α(TNF-α),核因子κB(NF-κB),白细胞介素-1β（IL-1β），白细胞介素-6（IL-6），c-JunNH2末端激酶（JNK），丝裂原活化蛋白激酶14（MAPK14），MAPK15，肝组织中的晚期糖基化终产物（RAGE）和节点样受体家族含pyrin结构域3（NLRP3）的受体。还通过提高激活转录因子6（ATF-6）的mRNA转录水平产生内质网应激，蛋白激酶RNA样ER激酶（PERK），需要肌醇的酶1（IRE1），和葡萄糖调节蛋白78（GRP-78）。这些因素共同导致炎症，凋亡，和内质网应激。另一方面,以25和50mg/kg的剂量用ZN处理的肝组织显示出氧化应激的显着改善，炎症,细胞凋亡和内质网应激。
结论：总体而言，研究数据表明，给予ZN可能能够减轻SA毒性引起的肝损伤。
