title: Molsidomine prevents cisplatin-induced hepatotoxicity.
abstract: OBJECTIVE
  Despite its beneficial effects, cisplatin has considerable nephrotoxic, ototoxic, neurotoxic and hepatotoxic side effects. It has been documented that reactive oxygen radical species are involved with the pathophysiology of cisplatin-induced hepatotoxicity. Molsidomine (MOL) can exert antioxidant and anti-inflammatory effects. Therefore, the current study was planned to determine the effects of cisplatin on the liver oxidant/antioxidant system and the possible protective effects of (MOL) on liver toxicity.
  
  
  METHODS
  Animals were divided into four groups as follows: (1) control; (2) MOL; (3) cisplatin and (4) MOL plus cisplatin group. Biochemical and histopathological evaluations were performed on the extracted liver tissue. Also, serum levels of serum aspartate transaminase (AST) and serum alanine transaminase (ALT) were determined.
  
  
  RESULTS
  Our results clearly indicated that liver antioxidant enzyme activities and ALT levels were significantly decreased, whereas lipid peroxidation and neutrophil accumulation were increased in the cisplatin-treated animals (5 mg/kg single dose, i.p.) compared to the control rats. MOL treatment (4 mg/kg/day, i.p.) for 3 consecutive days provided a significant protection against cisplatin-induced hazardous changes in the liver tissue. Our histopathological findings including caspase-3 activity were also in accordance with the biochemical results.
  
  
  CONCLUSIONS
  We propose that MOL acts in the liver as a potent scavenger of free radicals, anti-inflammatory and anti-apoptotic effects to prevent the toxic effects of cisplatin, both at the biochemical and histopathological levels.
authors.affiliation: Department of Internal Medicine, Medical Faculty, Inonu University, Malatya, Turkey. Electronic address: dr_bentli@hotmail.com.
authors.forename: Recep
authors.initials: R
authors.lastname: Bentli
authors.forename: Hakan
authors.initials: H
authors.lastname: Parlakpinar
authors.forename: Alaadin
authors.initials: A
authors.lastname: Polat
authors.forename: Emine
authors.initials: E
authors.lastname: Samdanci
authors.forename: Mehmet Ediz
authors.initials: ME
authors.lastname: Sarihan
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sagir
mesh_terms: D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002945:Cisplatin / Q000009:adverse effects* / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008981:Molsidomine / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D008981:Molsidomine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D002945:Cisplatin
keywords: Cisplatin; Liver; Molsidomine; Oxidative stress