TY - JOUR
T1 - Caffeine mitigates experimental nonalcoholic steatohepatitis and the progression of thioacetamide-induced liver fibrosis by blocking the MAPK and TGF-β/Smad3 signaling pathways
AU - Vargas-Pozada, Eduardo E.
AU - Ramos-Tovar, Erika
AU - Acero-Hernández, Consuelo
AU - Cardoso-Lezama, Irina
AU - Galindo-Gómez, Silvia
AU - Tsutsumi, Víctor
AU - Muriel, Pablo
N1 - Publisher Copyright:
© 2022 Fundación Clínica Médica Sur, A.C.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - Introduction and objectives: Caffeine consumption is associated with beneficial effects on hepatic disorders. The objectives of this study were to evaluate the antifibrotic effects of caffeine on experimental nonalcoholic steatohepatitis (NASH) induced with a high-fat, high-sucrose, high-cholesterol diet (HFSCD), as well as to evaluate the ability of caffeine to prevent the progression of experimental liver fibrosis induced by the administration of thioacetamide (TAA) in rats and explore the mechanisms of action. Methods: NASH and fibrosis were induced in rats by the administration of an HFSCD for 15 weeks, and liver fibrosis was induced by intraperitoneal administration of 200 mg/kg TAA 3 times per week, for 6 weeks. Caffeine was administered at a dose of 50 mg/kg body weight. The effects of diet, TAA, and caffeine on fibrosis were evaluated by biochemical and histological examinations. The profibrotic pathways were analyzed by western blotting and immunohistochemistry. Results: Rats exhibited liver fibrosis after HFSCD feeding and the administration of TAA. Caffeine could reduce the hepatic level of collagen and the fibrotic area in the liver. Caffeine prevented the progression of liver fibrosis by decreasing transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (α-SMA) expression and by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and Smad3 phosphorylation. Conclusions: Caffeine attenuates NASH and the progression of liver fibrosis due to its antifibrotic effects and modulating the MAPK and TGF-β pathways. Therefore, caffeine could be a suitable candidate for treating liver diseases associated with fibrosis.
AB - Introduction and objectives: Caffeine consumption is associated with beneficial effects on hepatic disorders. The objectives of this study were to evaluate the antifibrotic effects of caffeine on experimental nonalcoholic steatohepatitis (NASH) induced with a high-fat, high-sucrose, high-cholesterol diet (HFSCD), as well as to evaluate the ability of caffeine to prevent the progression of experimental liver fibrosis induced by the administration of thioacetamide (TAA) in rats and explore the mechanisms of action. Methods: NASH and fibrosis were induced in rats by the administration of an HFSCD for 15 weeks, and liver fibrosis was induced by intraperitoneal administration of 200 mg/kg TAA 3 times per week, for 6 weeks. Caffeine was administered at a dose of 50 mg/kg body weight. The effects of diet, TAA, and caffeine on fibrosis were evaluated by biochemical and histological examinations. The profibrotic pathways were analyzed by western blotting and immunohistochemistry. Results: Rats exhibited liver fibrosis after HFSCD feeding and the administration of TAA. Caffeine could reduce the hepatic level of collagen and the fibrotic area in the liver. Caffeine prevented the progression of liver fibrosis by decreasing transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and alpha-smooth muscle actin (α-SMA) expression and by inhibiting the activation of mitogen-activated protein kinases (MAPKs) and Smad3 phosphorylation. Conclusions: Caffeine attenuates NASH and the progression of liver fibrosis due to its antifibrotic effects and modulating the MAPK and TGF-β pathways. Therefore, caffeine could be a suitable candidate for treating liver diseases associated with fibrosis.
KW - Caffeine
KW - Experimental NASH
KW - Fibrosis
KW - MAPK, TGF-β
KW - Thioacetamide
UR - http://www.scopus.com/inward/record.url?scp=85123774872&partnerID=8YFLogxK
U2 - 10.1016/j.aohep.2022.100671
DO - 10.1016/j.aohep.2022.100671
M3 - Artículo
C2 - 35065262
AN - SCOPUS:85123774872
SN - 1665-2681
VL - 27
JO - Annals of Hepatology
JF - Annals of Hepatology
IS - 2
M1 - 100671
ER -