TY - JOUR
T1 - The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat
AU - Fernández-Martínez, Eduardo
AU - Pérez-Hernández, Nury
AU - Muriel, Pablo
AU - Pérez-Álvarez, Víctor
AU - Shibayama, Mineko
AU - Tsutsumi, Víctor
N1 - Funding Information:
The authors thank to Q.F.I. Isabel Wens-Flores, Biol. Mario G. Moreno, M.V.Z. Ricardo Gaxiola, Mr. Ramón Hernández and Mr. Benjamín Salinas for their excellent technical assistance. This work was in part supported by grant number PAI-2006-60B from UAEH and partially by grant number 50733-Q from Consejo Nacional de Ciencia y Tecnología (CONACyT), Mexico.
PY - 2009/9
Y1 - 2009/9
N2 - Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), γ-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.
AB - Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), γ-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.
KW - Bile duct ligation
KW - Cholestasis
KW - Cirrhosis
KW - Fibrosis
KW - Liver
KW - Necrosis
KW - Thalidomide
KW - Thalidomide analogs
UR - http://www.scopus.com/inward/record.url?scp=68349141423&partnerID=8YFLogxK
U2 - 10.1016/j.etp.2008.11.001
DO - 10.1016/j.etp.2008.11.001
M3 - Artículo
SN - 0940-2993
VL - 61
SP - 471
EP - 479
JO - Experimental and Toxicologic Pathology
JF - Experimental and Toxicologic Pathology
IS - 5
ER -