We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and alpha-smooth muscle actin (alpha SMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius red-stained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-I and TGF-beta 1 mRNA levels and aSMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Gagliano, N., Donne, I., Torri, C., Migliori, M., Grizzi, F., Milzani, A., et al. (2006). Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study. TOXICOLOGY, 225(2-3), 214-224 [10.1016/j.tox.2006.06.004].

Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study

ANNONI, GIORGIO;
2006

Abstract

We characterized the overall early effect of chronic ochratoxin A (OTA) treatment on rat liver, analyzing different aspects related to: (i) fibrosis, by measuring collagen content and turnover, and alpha-smooth muscle actin (alpha SMA); (ii) oxidative stress and stress response, by analyzing protein carbonylation, superoxide dismutase (SOD) and heat shock protein (HSP70) gene expression; (iii) the possible tumor promoter effect, evaluating cadherin and connexin (CX) mRNA levels. Light microscopy analysis showed no histological differences in OTA-treated and control (CT) rats. Collagen content, determined by computer analysis of Sirius red-stained liver sections, was similar in both groups. In liver homogenates COL-I, COL-III, TIMP-I and TGF-beta 1 mRNA levels and aSMA were unaffected by OTA. Matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 protein levels were also similar in the two groups. Protein carbonylation, a marker of severe oxidative stress, was not evident in the homogenates of OTA-treated livers; superoxide dismutase (SOD) mRNA tended to be lower and HSP70 was strongly down-regulated. OTA reduced E-cadherin and DSC-2 transcription, and down-regulated liver CX26, CX32 and CX43. In conclusion, these in vivo results show that OTA-induced liver injury involves a reduction in the ability to counterbalance oxidative stress, maybe leading to altered gap junction intercellular communication and loss of cell adhesion and polarity. This suggests that mild oxidative damage might be a key factor, in combination with other cytotoxic effects, in triggering the promotion of liver tumors after exposure to OTA. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
Articolo in rivista - Articolo scientifico
ochratoxin A; collagen turnover; oxidative stress; cadherins; connexins; HSP70
English
15-ago-2006
225
2-3
214
224
open
Gagliano, N., Donne, I., Torri, C., Migliori, M., Grizzi, F., Milzani, A., et al. (2006). Early cytotoxic effects of ochratoxin A in rat liver: A morphological, biochemical and molecular study. TOXICOLOGY, 225(2-3), 214-224 [10.1016/j.tox.2006.06.004].
File in questo prodotto:
File Dimensione Formato  
749.pdf

accesso aperto

Dimensione 369.46 kB
Formato Adobe PDF
369.46 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/749
Citazioni
  • Scopus 82
  • ???jsp.display-item.citation.isi??? 78
Social impact