title: Suppressing cyclooxygenase-2 prevents nonalcoholic and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway.
abstract: Cyclooxygenase-2 (COX-2) can exert pro-inflammatory effects in nonalcoholic steatohepatitis (NASH). The aim of this study was to determine if the inhibition of COX-2 attenuates hepatocyte apoptosis in steatohepatitis and to examine the underlying molecular mechanism. Male wild type C57BL6/J mice and COX-2 knock out (COX-2-/-) mice were fed a methionine choline deficient (MCD) diet for 3 weeks. The wild type mice were also treated with celecoxib or a combination of celecoxib and a Akt specific inhibitor, miltefosine (MTF). After that, liver histology, serum alanine aminotransferase (ALT) levels, hepatic triglyceride (TG) levels, hepatocyte apoptosis, phosphorylated Akt (Ser473, pAkt) and p53 protein levels in mice livers were assessed. Celecoxib attenuated the severity of liver steatohepatitis and reduced the number of apoptotic cells, accompanied by increasing the activity of Akt and decreasing expression of p53. On the contrary, MTF can abrogate the effects of celecoxib on anti-apoptosis and anti-steatohepatitis. Moreover, the effects on the COX-2-/- mice that were fed the MCD diet were similar to that for celecoxib. The findings suggested that suppressing COX-2 can improve steatohepatitis by inhibiting hepatocyte apoptosis in mice via regulating the Akt/p53 pathway. Celecoxib treatment may be a favorable treatment option for NASH.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Jialing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Xianbin
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Qinjia
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Bozhi
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China. Electronic address: xbjing@stu.edu.cn.
authors.forename: Xubin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib / Q000008:administration & dosage; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004268:DNA-Binding Proteins; C114495:TP53TG1 protein, human; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051058:Oncogene Protein v-akt; D000068579:Celecoxib
keywords: Akt; Apoptosis; COX-2; Celecoxib; Nonalcoholic steatohepatitis; p53