title: Thymoquinone alleviates nonalcoholic fatty liver disease in rats via suppression of oxidative stress, inflammation, apoptosis.
abstract: Nonalcoholic steatohepatitis (NAFLD) is a progressive form of liver disease that leads to advanced fibrosis. The present study was designed to assess the hepatoprotective effect of thymoquinone (TQ) on liver functions, insulin resistance, and PPAR-γ expression in NAFLD. Rats were divided into two main groups: one fed with normal rat chow diet and the other with high-fat high-cholesterol diet group for 6 weeks. Every group was subdivided into three subgroups (n = 8): treated with saline, low dose TQ (10 mg/kg), high dose TQ (20 mg/kg). High fat high cholesterol diet caused marked liver damage as noted in histopathology and significant increase in liver index, liver enzymes. There was significant increase in the insulin resistance, serum cholesterol, triglyceride, PPAR-γ gene overexpression with significant decrease in HDL. Additionally, oxidative stress increased by measuring MDA associated with significant decrease in serum total antioxidant capacity. As markers of inflammation, hepatic TNF-α was significantly increased with decrease in IL10. Further, there was increase in BAX protein with decrease in Bcl as compared to control group. This model of 6 weeks high-fat high-cholesterol diet showed minimal fibrosis as noticed by increase MMP2 and Masson trichrome satin. Co-treatment with TQ improved all previous parameters. High dose was more effective, although mostly non-statistically significant. TQ may have a promising agent to improve hepatic steatosis, oxidative stress; inflammatory, apoptotic status, fibrosis and so prevent liver damage in patients with NAFLD. Although PPAR-γ was significantly under-expressed by TQ, insulin resistance was improved significantly suggesting a role of liver damage.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy for Girls, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: Azza S M
authors.initials: AS
authors.lastname: Awad
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy for Girls, Al-Azhar University, Nasr City, Cairo, Egypt.
authors.forename: Ekram N
authors.initials: EN
authors.lastname: Abd Al Haleem
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. w_bakly@yahoo.com.
authors.forename: Wesam M
authors.initials: WM
authors.lastname: El-Bakly
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Benha University, Al Qalyubia Governorate, Egypt.
authors.forename: Mohie A
authors.initials: MA
authors.lastname: Sherief
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D059305:Diet, High-Fat; D006505:Hepatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; C494828:Bax protein, rat; D016227:Benzoquinones; D018836:Inflammation Mediators; D008055:Lipids; D047495:PPAR gamma; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016753:Interleukin-10; C003466:thymoquinone
keywords: Alcoholic steatohepatitis; Insulin resistance; PPAR-γ; TNF-α; Thymoquinone