Methanol extract of Iphiona aucheri ameliorates CCl4 induced hepatic injuries by regulation of genes in rats

• Published in: Toxicology research (Cambridge) 2019-11, Vol.8 (6), p.815-832
• Main Authors: Zai, Jawaid Ahmed, Khan, Muhammad Rashid, Mughal, Zaib un Nisa, Batool, Riffat, Naz, Irum, Maryam, Sonia, Zahra, Zartash
• Format: Article
• Language: English
• Subjects: Actin; Alanine; Alanine transaminase; Alkaline phosphatase; Antioxidants; Aspartate aminotransferase; Bilirubin; Carbon tetrachloride; Catalase; CCAAT/enhancer-binding protein; CCL4 protein; Chemical compounds; Collagen (type I); Endoplasmic reticulum; Fibrosis; Gene expression; Gene regulation; Genes; Glutathione; Growth factors; Homology; Inflammation; Intoxication; Liver; Methanol; Muscles; Oxidative stress; Peroxidase; Pharmacology; Proteins; Skeletal muscle; Superoxide dismutase; Toxicity; Transforming growth factor-b; Tumor necrosis factor-TNF
• ISSN: 2045-4538; 2045-452X; 2045-4538
• DOI: 10.1039/c9tx00157c

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.