Jonathan Arauz1, Yadira Rivera-Espinoza2, Mineko Shibayama3, Liliana Favari4, Rosa Elena Flores-Beltrán4, Pablo Muriel5. 1. Departamento de Farmacología, Escuela de Medicina, Universidad Autónoma de Baja California, Mexicali, Baja California, Mexico. Electronic address: jarauz@uabc.edu.mx. 2. Departamento de Ingeniería Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico D.F., Mexico. 3. Departamento de Infectómica y Patogénesis Molecular, Cinvestav-IPN., Mexico D.F., Mexico. 4. Departamento de Farmacología, Cinvestav-IPN., Mexico D.F., Mexico. 5. Departamento de Farmacología, Cinvestav-IPN., Mexico D.F., Mexico. Electronic address: pmuriel@cinvestav.mx.
Abstract
UNLABELLED: 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.
UNLABELLED: 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: Jan Stastny; Petr Marsik; Jan Tauchen; Matej Bozik; Anna Mascellani; Jaroslav Havlik; Premysl Landa; Ivan Jablonsky; Jakub Treml; Petra Herczogova; Roman Bleha; Andriy Synytsya; Pavel Kloucek Journal: Antioxidants (Basel) Date: 2022-08-13