title: Protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.
abstract: OBJECTIVE
  To study the protective effects of tiopronin against high fat diet-induced non-alcoholic steatohepatitis in rats.
  
  
  METHODS
  Male Sprague-Dawley rats were given a high-fat diet for 10 weeks. The rats were administered tiopronin (20 mg/kg) or a positive control drug ursodeoxycholic acid (UDCA, 15 mg/kg) via gavage daily from week 5 to week 10. After the rats were sacrificed, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C), and liver homogenate FFA, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured using commercial analysis kits. The expression levels of CYP2E1 mRNA and protein were determined using RT-PCR and immunoblot assays, respectively.
  
  
  RESULTS
  Tiopronin significantly lowered both the serum ALT and AST levels, while only the serum ALT level was lowered by UDCA. Tiopronin significantly decreased the serum and liver levels of TG, TC and FFA as well as the serum LDL-C level, and increased the serum HDL-C level, while UDCA decreased the serum and liver TC levels as well as the serum LDL-C level, but did not change the serum levels of TG, FFA and HDL-C. Tiopronin apparently ameliorated the hepatocyte degeneration and the infiltration of inflammatory cells in the livers, but UDCA did not affect the pathological features of the livers. Both tiopronin and UDCA ameliorated the mitochondrial abnormality in the livers. The benefits of tiopronin were associated with increased SOD and GSH-Px activities, and with decreased MDA activity and CYP2E1 expression in the livers.
  
  
  CONCLUSIONS
  Tiopronin exerts protective effects against non-alcoholic steatohepatitis in rats, which may be associated with its antioxidant properties and regulation of lipid metabolism.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei, China.
authors.forename: Jian-qing
authors.initials: JQ
authors.lastname: Wang
authors.forename: Yu-hong
authors.initials: YH
authors.lastname: Zou
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Chao
authors.initials: C
authors.lastname: Lu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Jin
authors.forename: Xiong-wen
authors.initials: XW
authors.lastname: Lü
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D008625:Tiopronin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D008625:Tiopronin; D019392:Cytochrome P-450 CYP2E1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase