RT info:eu-repo/semantics/article
T1 Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice
A1 Crespo, Irene
A1 San-Miguel, Beatriz
A1 Fernández, Ana
A1 Ortiz de Urbina, Juan
A1 González Gallego, Javier
A1 Tuñón González, María Jesús
A2 Otros
K1 Medicina. Salud
K1 Melatonin
K1 Profibrogenic
K1 Hepatic fibrosis
K1 Ameliorates
AB We investigated whether melatonin ameliorates fibrosis and limits the expression offibrogenic genes in mice treated with carbon tetrachloride (CCl4). Mice in treatmentgroups received CCl4 5 mL/g body weight intraperitoneally twice a week for 4 or6 weeks. Melatonin was given at 5 or 10 mg/kg/d intraperitoneally, beginning2 weeks after the start of CCl4 administration. Treatment with CCl4 resulted in fibrosisevidenced by the staining of Van Gieson and a-smooth muscle actin (a-SMA) positivecells in the liver. At both 4 and 6 weeks, CCl4 induced an increase in themessenger RNA levels of collagens I and III, transforming growth factor (TGF)-b,platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), amphiregulin,matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase(TIMP)-1. Protein concentrations of CTGF, amphiregulin, MMP-9, TIMP-1, andphospho-Smad3 were also significantly augmented in fibrotic mice. Melatonin successfullyattenuated liver injury, as shown by histopathology and decreased levels ofserum transaminases. Immunohistochemical staining of a-SMA indicated an abrogationof hepatic stellate cell activation by the indol. Furthermore, melatonin treatmentresulted in significant inhibition of the expression of collagens I and III, TGF-b,PDGF, CTGF, amphiregulin, and phospho-Smad3. The MMP-9 activity decreasedand the expression of nuclear factor erythroid–2–related factor 2 (Nrf2) increasedin mice receiving melatonin. Data obtained suggest that attenuation of multiple profibrogenicgene pathways contributes to the beneficial effects of melatonin in micewith CCl4-induced liver fibrosis
PB Elsevier
YR 2016
FD 2016-12-19
LK http://hdl.handle.net/10612/5691
UL http://hdl.handle.net/10612/5691
NO Translational Research, 2015, vol. 165, n. 2
NO P. 346-357
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 18-abr-2024