title: Nicotinic acid prevents experimental liver fibrosis by attenuating the prooxidant process.
abstract: Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most chronic liver diseases. Nicotinamide treatment has been shown to prevent collagen accumulation and fibrogenesis in a bleomycin model of lung fibrosis. In this study, we evaluated the effects of nicotinic acid (NA) on experimental liver fibrosis and investigated its underlying mechanism.
  
  
  METHODS
  Fibrosis was induced by chronic TAA administration and the effects of co-administration with NA for 8 weeks were evaluated, including control groups.
  
  
  RESULTS
  TAA administration induced liver fibrosis, which was prevented by nicotinic acid. NA prevented the elevation of liver enzymes and prevented hepatic glycogen depletion. Liver histopathology and hydroxyproline levels were significantly lower in the rats treated with TAA plus NA compared with TAA only. NA demonstrated antioxidant properties by restoring the redox equilibrium (lipid peroxidation and GPx levels). Western blot assays showed decreased expression levels of TGF-β and its downstream inductor CTGF. Additionally, NA prevented hepatic stellate cell activation due by blocking the expression of α-SMA. Zymography assays showed that NA decreased the activity of matrix metalloproteinases 2 and 9.
  
  
  CONCLUSIONS
  NA prevents experimental fibrosis; the mechanisms of action are associated with its antioxidant properties and the reduction in TGF-β expression. The decrease in TGF-β levels may be associated with the attenuation of the oxidative processes, thus resulting in a reduction in HSC activation and ECM deposition. The findings suggest a possible role for NA as an antifibrotic agent for liver injury.
authors.affiliation: Departamento de Farmacología, Escuela de Medicina, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico. Electronic address: jarauz@uabc.edu.mx.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Arauz
authors.affiliation: Departamento de Ingeniería Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico D.F., Mexico.
authors.forename: Yadira
authors.initials: Y
authors.lastname: Rivera-Espinoza
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Cinvestav-IPN., Mexico D.F., Mexico.
authors.forename: Mineko
authors.initials: M
authors.lastname: Shibayama
authors.affiliation: Departamento de Farmacología, Cinvestav-IPN., Mexico D.F., Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Favari
authors.affiliation: Departamento de Farmacología, Cinvestav-IPN., Mexico D.F., Mexico.
authors.forename: Rosa Elena
authors.initials: RE
authors.lastname: Flores-Beltrán
authors.affiliation: Departamento de Farmacología, Cinvestav-IPN., Mexico D.F., Mexico. Electronic address: pmuriel@cinvestav.mx.
authors.forename: Pablo
authors.initials: P
authors.lastname: Muriel
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D055513:Connective Tissue Growth Factor / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D009525:Niacin / Q000627:therapeutic use*; D016877:Oxidants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000199:Actins; D000975:Antioxidants; D055513:Connective Tissue Growth Factor; D006003:Glycogen; D020782:Matrix Metalloproteinases; D009525:Niacin; D016877:Oxidants; D013853:Thioacetamide; D016212:Transforming Growth Factor beta; C526316:CCN2 protein, rat; C498862:Acta2 protein, rat
keywords: Antioxidants; Cirrhosis; Fibrosis; Inflammation; Nicotinic acid