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Methanol extract of Iphiona aucheri ameliorates CCl4 induced hepatic injuries by regulation of genes in rats
Toxicology Research ( IF 2.2 ) Pub Date : 2019-11-14 , DOI: 10.1039/c9tx00157c
Jawaid Ahmed Zai 1 , Muhammad Rashid Khan 1 , Zaib Un Nisa Mughal 1 , Riffat Batool 1 , Irum Naz 1 , Sonia Maryam 1 , Zartash Zahra 1
Affiliation  

We have investigated the protective potential of methanol extract of Iphiona aucheri (IAM) on the expression of endoplasmic reticulum (ER) stress associated genes and inflammatory genes on carbon tetrachloride (CCl4) induced hepatic toxicity in rats. Hepatic damage markers: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin were elevated while the content of antioxidants: catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and reduced glutathione (GSH) were decreased significantly (p < 0.05) in CCl4 treated rats as compared to the control group. The CCl4 intoxication induced a higher expression of glucose-regulated protein 78 kDa (GRP78), X-box-binding protein 1 total (XBP1t), spliced X-box-binding protein 1 (XBP1s), unspliced X-box-binding protein 1 (XBP1u), C/EBP homologous protein (CHOP) and genes involved in inflammation and fibrosis: tumor necrosis factor alpha (TNF-α), transforming growth factor-beta (TGF-β), mothers against DPP homolog 3 (SMAD3), alpha skeletal muscle actin (αSMA) and collagen type I alpha 1 chain (COL1A1). The intoxicated rats showed a low expression of the glutamate–cysteine ligase catalytic subunit (GCLC), protein disulfide isomerase (PDI) and nuclear factor (erythroid-derived 2) like-2 (Nrf2). The administration of IAM to intoxicated rats restored the expression of ER stress, inflammatory, fibrosis and antioxidant genes in a dose dependent manner. Our results indicated that IAM can impede the ER stress and inflammatory genes and it could be a complementary and alternative therapeutic agent for oxidative stress associated disorders.

中文翻译:

Iphiona aucheri 甲醇提取物通过调节基因改善 CCl4 诱导的大鼠肝损伤

我们研究了Iphiona aucheri (IAM) 的甲醇提取物对四氯化碳 (CCl 4 ) 诱导的大鼠肝毒性中内质网 (ER) 应激相关基因和炎症基因表达的保护潜力。肝损伤标志物:天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、碱性磷酸酶(ALP)和胆红素升高,抗氧化剂:过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、过氧化物酶(POD)和还原型谷胱甘肽含量升高。与对照组相比, CCl 4处理组大鼠中GSH 显着降低(p < 0.05) 。CCl 4中毒诱导葡萄糖调节蛋白 78 kDa (GRP78)、X-box 结合蛋白 1 总 (XBP1t)、剪接 X-box 结合蛋白 1 (XBP1s)、未剪接 X-box 结合蛋白的较高表达1 (XBP1u)、C/EBP 同源蛋白 (CHOP) 以及参与炎症和纤维化的基因:肿瘤坏死因子 α (TNF-α)、转化生长因子 β (TGF-β)、Mothers against DPP 同源蛋白 3 (SMAD3) 、α 骨骼肌肌动蛋白 (αSMA) 和 I 型胶原蛋白 α 1 链 (COL1A1)。中毒大鼠的谷氨酸-半胱氨酸连接酶催化亚基(GCLC)、蛋白质二硫键异构酶(PDI)和核因子(红细胞衍生2)like-2(Nrf2)表达低。对中毒大鼠施用 IAM 以剂量依赖性方式恢复 ER 应激、炎症、纤维化和抗氧化基因的表达。我们的结果表明,IAM 可以阻碍 ER 应激和炎症基因,它可以作为氧化应激相关疾病的补充和替代治疗剂。
更新日期:2019-11-14
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