TY - JOUR
T1 - Nicotinic acid prevents experimental liver fibrosis by attenuating the prooxidant process
AU - Arauz, Jonathan
AU - Rivera-Espinoza, Yadira
AU - Shibayama, Mineko
AU - Favari, Liliana
AU - Flores-Beltrán, Rosa Elena
AU - Muriel, Pablo
N1 - Publisher Copyright:
© 2015 Published by Elsevier B.V.
PY - 2015/6/22
Y1 - 2015/6/22
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Cirrhosis
KW - Fibrosis
KW - Inflammation
KW - Nicotinic acid
UR - http://www.scopus.com/inward/record.url?scp=84934929579&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2015.05.045
DO - 10.1016/j.intimp.2015.05.045
M3 - Artículo
SN - 1567-5769
VL - 28
SP - 244
EP - 251
JO - International Immunopharmacology
JF - International Immunopharmacology
IS - 1
ER -