title: Celecoxib attenuates liver steatosis and inflammation in non-alcoholic steatohepatitis induced by high-fat diet in rats.
abstract: Cyclooxygenase-2 (COX-2) is involved in the process of non-alcoholic steatohepatitis (NASH). However, the role of the COX-2 inhibitor in NASH has not yet been elucidated. Therefore, in the present study, we investigated the role of celecoxib in a rat model of NASH induced by a high-fat diet (HFD). Wistar rats were administered HFD by gavage, and rats administered normal saline by gavage served as the controls. After 4 weeks of HFD feeding, the rats were treated with celecoxib (20 mg/kg/day) or placebo for 4 weeks. At the end of 4 and 8 weeks, histological changes in the livers of the rats were analyzed using hematoxylin and eosin; blood was collected to detect biochemical indicators (serum aminotransferase and triglyceride). Liver triglyceride content was measured using the triglyceride E-test kit. The liver expression of COX-2, nuclear factor-κ enhancer binding protein (NF-κB) subunits p50 and p65 was measured by real-time reverse transcription-polymerase chain reaction and/or Western blotting. Infiltration of steatosis and inflammation in cells was observed in the livers after 4 weeks of HFD administration, and marked steatosis and inflammation was induced after 8 weeks. These histological changes were significantly attenuated after celecoxib treatment. Reduced serum alanine aminotransferase and triglyceride (TG) levels and TG content in the liver were observed in the HFD rats that received celecoxib. Moreover, celecoxib suppressed hepatic COX-2 messenger RNA and protein expression. The NF-κB subunit p50 and p65 protein levels in the HFD rats were also attenuated after celecoxib treatment. The results indicate that the induction of COX-2 occurs in association with NF-κB activation in HFD-induced NASH rats. Celecoxib may protect against the development of steatohepatitis induced by HFD.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Nangang, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Diangang
authors.initials: D
authors.lastname: Liu
authors.forename: Qixuan
authors.initials: Q
authors.lastname: Bai
authors.forename: Jitao
authors.initials: J
authors.lastname: Song
authors.forename: Jia
authors.initials: J
authors.lastname: Guan
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.forename: Bingrong
authors.initials: B
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Yaju
authors.initials: Y
authors.lastname: Du
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D004041:Dietary Fats; D016328:NF-kappa B; D011720:Pyrazoles; D013449:Sulfonamides; D014280:Triglycerides; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000410:Alanine Transaminase; D000068579:Celecoxib