Pathogenic role of oxidative and nitrosative stress in primary biliary cirrhosis

Table 1 Time-related changes of glutathione peroxidase and glutathione reductase activities in liver cytosol and mitochondria of sham-operated and bile duct ligated rats

Cytosol	Day 0	Sham Day 3	BDL Day 3	Sham Day 10	BDL Day 10
GSH-Px	351 ± 32	336 ± 35	504 ± 541	335 ± 20	566 ± 3212
GSSG-Rx	0.31 ± 0.11	0.27 ± 0.10	0.37 ± 0.081	0.28 ± 0.05	0.60 ± 0.1012
Mitochondria
GSH-Px	977 ± 27	913 ± 44	1061 ± 95	890 ± 42	1568 ± 10512
GSSG-Rx	1.12 ± 0.17	0.93 ± 0.09	1.33 ± 0.121	0.89 ± 0.07	1.98 ± 0.1212

Glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Rx) are reported as mU/mg protein/minute. Significantly different (0.01 < P < 0.05) compared to

¹baseline and

²sham-operated rats at each time point. Adapted from Grattagliano and Portincasa (unpublished data). Enzyme activities assessed as previously described[58]. BDL: Bile duct ligation.

Table 2 Therapeutic doses of ursodeoxycholic acid and its potential effects in the treatment of patients with primary biliary cirrhosis

Effective dose: 13-15 mg/kg per day indefinitely

Mechanisms of action

Promotion of endogenous bile acids secretion

Replacement of hepatotoxic (endogenous) bile acids

Stabilization of biliary epithelial cell membranes

Alteration of HLA I-II expression on biliary epithelial cell

Inhibition of biliary cell apoptosis

Improvement of hepatocyte redox status

Signaling for glucose and insulin metabolic pathways

Delays disease progression and improves transplant-free survival