title: Telmisartan improves nonalcoholic steatohepatitis in medaka (Oryzias latipes) by reducing macrophage infiltration and fat accumulation.
abstract: We investigated the efficacy of the antihypertensive drug telmisartan (Tel) and the mechanisms underlying the progression from simple steatosis to nonalcoholic steatohepatitis (NASH) in a medaka (Oryzias latipes) NASH model. We used the NASH activity score (NAS) developed in humans to assess the histology of the medaka NASH model and found that NAS increased with time. Further, TUNEL-positive apoptosis hepatocytes were found in the medaka NASH model. Tel administration resulted in the increased expression of liver peroxisome proliferator-activated receptor-γ, carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 and decreased the number of 8-hydroxydeoxyguanosine-positive hepatocytes and the migration of macrophages positive for diastase-periodic-acid-Schiff. Medaka NAS was improved by Tel administration but fatty acid content was not affected. Tel reduced the infiltration of macrophages into the liver and ameliorated NASH pathology.
authors.affiliation: Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi, 755-8505, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kuwashiro
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Oishi
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D005223:Fats / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease; D009990:Oryzias / Q000378:metabolism*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics; D000077333:Telmisartan; D015430:Weight Gain / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D005223:Fats; D047495:PPAR gamma; D002334:Carnitine O-Palmitoyltransferase; D000077333:Telmisartan