title: Protective Effects of Apocynin on Cisplatin-induced Hepatotoxicity in Rats.
abstract: OBJECTIVE
  Despite it being a highly potent antineoplastic drug, cisplatin has important toxic adverse effects limiting its use such as nephrotoxicity, neurotoxicity and ototoxicity. It is thought that cisplatin-induced hepatotoxicity is caused by oxidative stress resulting from increased reactive oxygen species (ROS). Apocynin (APO) exerts its antioxidant effect by reducing ROS production via inhibition of NADPH oxidase. The present study intended to demonstrate effects of cisplatin on hepatic pro-oxidant/antioxidant systems and to investigate protective effects of APO against cisplatin-induced hepatotoxicity.
  
  
  METHODS
  Rats were randomly assigned into four groups (n = 8 each): a) control group; b) single dose of cisplatin (5 mg/kg); c) APO group (20 mg/kg on three consecutive days; i.p.); and d) APO plus cisplatin group. Liver tissue was assessed in all groups by biochemical and histopathological means. Also, serum alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase levels were studied in all groups.
  
  
  RESULTS
  When cisplatin group was compared to controls, it was seen that lipid peroxidation product, total oxidant status and ALT levels were markedly increased, whereas superoxide dismutase and glutathione peroxidase levels were overtly decreased. APO therapy markedly prevented cisplatin-induced harmful changes in liver. Our histopathological findings such as central vein dilatation, perivenuler and periportal sinusoidal dilatation, parenchymal inflammation, vacuolar changes in hepatocytes, biliary duct proliferation and caspase-3 positive hepatocytes were in accordance with the biochemical changes.
  
  
  CONCLUSIONS
  In light of these results, it is our thought that APO has a protective role against cisplatin-induced hepatotoxicity at both biochemical and histopathological levels.
authors: Department of Gastroenterology, Medical Faculty, Inonu University, Malatya, Turkey. Electronic address: yasir.cagin@inonu.edu.tr.
authors: Yasir Furkan
authors: YF
authors: Cagin
authors: Department of Gastroenterology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Mehmet Ali
authors: MA
authors: Erdogan
authors: Department of Pathology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Nurhan
authors: N
authors: Sahin
authors: Department of Pharmacology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Hakan
authors: H
authors: Parlakpinar
authors: Department of Gastroenterology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Yahya
authors: Y
authors: Atayan
authors: Department of Physiology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Alaadin
authors: A
authors: Polat
authors: Department of Histology and Embryology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Nigar
authors: N
authors: Vardi
authors: Department of Histology and Embryology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Azibe
authors: A
authors: Yildiz
authors: Department of Physiology, Medical Faculty, Inonu University, Malatya, Turkey.
authors: Kevser
authors: K
authors: Tanbek
mesh_terms: D000098:Acetophenones / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; C056165:acetovanillone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D053148:Caspase 3; D002945:Cisplatin
keywords: Apocynin; Cisplatin; Hepatotoxicity; Oxidative stress