Cadmium induces alpha(1)collagen (I) and metallothionein II gene and alters the antioxidant system in rat hepatic stellate cells.
The mechanism of cadmium-mediated hepatotoxicity has been the subject of numerous investigations, principally in hepatocytes. Although, some uncertainties persist, sufficient evidence has emerged to provide a reasonable account of the toxic process in parenchymal cells. However, there is no information about the effect of cadmium in other hepatic cell types, such as stellate cells (fat storing cells, Ito cells, perisinusoidal cells, parasinusoidal cells, lipocytes). Hepatic stellate cells (HSC) express a quiescent phenotype in a healthy liver and acquire an activated phenotype in liver injury. These cells play an important role in the fibrogenic process. The objective of this study was to investigate the effect of a 24 h treatment of low Cd concentrations in glutathione content, lipid peroxidation damage, cytosolic free Ca, antioxidant enzyme activities: glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase along with the capacity of this heavy metal to induce metallothionein II and alpha(1)collagen (I) in an hepatic stellate cell line (CFSC-2G). Cd-treated cells increased lipid peroxidation and the content of cytosolic free calcium, decreased glutathione content and superoxide dismutase, glutathione peroxidase and catalase activity. Cd was able to induce the expression of the metallothionein II and alpha(1)collagen (I) gene, that was not described in this cell type. Cadmium may act as a pro-fibrogenic agent in the liver probably by inducing oxidative damage by enhancing lipid peroxidation and altering the antioxidant system of the cells. Although, the exact role metallothionein induction plays in this process is unknown, it probably, provides a cytosolic pool of potential binding sites to sequester ionic Cd, thereby decreasing its toxicity.
del Carmen
Escobar Ma
EM
Laboratorio de Fisiologia Celular, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-lztapalapa, Apdo Postal 55-535, D.F. 09340, Mexico.
Souza
Verónica
V
Bucio
Leticia
L
Hernández
Elizabeth
E
Damián-Matsumura
Pablo
P
Zaga
Verónica
V
Gutiérrez-Ruiz
Ma Concepción
MC
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015152:Blotting, Northern; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics*; D009499:Neutral Red; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D000975:Antioxidants; D024042:Collagen Type I; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D002104:Cadmium; D009499:Neutral Red; D008668:Metallothionein; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; C022616:thiazolyl blue; D005978:Glutathione; D002118:Calcium