Melatonin prevents experimental liver cirrhosis induced by thioacetamide in rats.
Liver cirrhosis is a critical stage of chronic liver diseases that can produce liver failure, portal hypertension and hepatocarcinoma. Sustained oxidative stress plays a key role in cell damage and fibrosis induced during liver cirrhosis. We evaluated the effect of oxidative stress regulation by melatonin on the development of parenchymal destruction and stellate cell activation in experimental liver cirrhosis. Melatonin was administered to rats with liver cirrhosis induced by thioacetamide (TAA) for 1 or 3 months. Liver injury was assessed by serological analysis, as well as hematoxylin-eosin staining and the in situ apoptosis detection assay in liver sections. Oxidative stress was evaluated by lipoperoxide and reduced glutathione levels, and by the measurement of catalase and superoxide dismutase activities in liver and serum respectively. The activation of stellate cells was evaluated by alpha-smooth muscle actin expression in liver sections. Our results showed that TAA induced oxidative stress with extensive tissue damage and enhanced alpha-smooth muscle actin expression in liver. Melatonin prevented the oxidative stress-related changes associated with TAA toxicity. In conclusion, the study showed that melatonin prevents the tissue damage and fibrosis associated with TAA-induced liver cirrhosis in rats.
Cruz
Adolfo
A
Department of General Surgery, Reina Sofia University Hospital, Córdoba, Spain.
Padillo
Francisco J
FJ
Torres
Eva
E
Navarrete
Carmen M
CM
Muñoz-Castañeda
Juan R
JR
Caballero
Francisco J
FJ
Briceño
Javier
J
Marchal
Trinidad
T
Túnez
Isaac
I
Montilla
Pedro
P
Pera
Carlos
C
Muntané
Jordi
J
D000818:Animals; D015415:Biomarkers; D002374:Catalase / Q000378:metabolism; D053938:DNA Fragmentation; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D013853:Thioacetamide
D015415:Biomarkers; D013853:Thioacetamide; D002374:Catalase; D013482:Superoxide Dismutase; D008550:Melatonin