There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
This study was designed to evaluate the effects of long-term treatment with alpha-naphthyl-isothiocyanate
(ANIT) on liver histology and at the mitochondrial bioenergetic level. Since, ANIT
has been used as a cholestatic agent and it has been pointed out that an impairment
of mitochondrial function is a cause of hepatocyte dysfunction leading to cholestatic
liver injury, serum markers of liver injury were measured and liver sections were
analyzed in ANIT-treated rats (i.p. 80 mg/kg/week x 16 weeks). Mitochondrial parameters
such as transmembrane potential, respiration, calcium capacity, alterations in permeability
transition susceptibility and ATPase activity were monitored. Histologically, the
most important features were the marked ductular proliferation, proliferation of mast
cells and the presence of iron deposits in ANIT-treated liver. Mitochondria isolated
from ANIT-treated rats showed no alterations in state 4 respiration, respiratory control
ratio and ADP/O ratio, while state 3 respiration was significantly decreased. No changes
were observed on transmembrane potential, but the repolarization rate was decreased
in treated rats. Consistently with these data, there was a significant decrease in
the ATPase activity of treated mitochondria. Associated with these parameters, mitochondria
from treated animals exhibited increased susceptibility to mitochondrial permeability
transition pore opening (lower calcium capacity). Since, human cholestatic liver disease
progress slowly overtime, these data provide further insight into the role of mitochondrial
dysfunction in the process.