Parallel intestinal and liver injury during early cholestasis in the rat: Modulation by bile salts and antioxidants

Pathophysiology of increased intestinal permeability in obstructive jaundice

“…Those researchers applying in vitro experiments with enterocytic monolayers incubated in the presence or absence of graded concentrations of bile showed that the alterations of intestinal tight junctions were bile mediated, while this finding was also supported in vivo because gavaging mice with rat bile significantly ameliorated the deleterious effects of obstructive jaundice on intestinal permeability. Also, in a current study it was shown that intestinal electrophysiological parameters in jaundiced animals, which substantially depend on intestinal TJs' integrity, were improved after oral supplementation with bile salts [39] . Further investigaton into the role in parallel with decreased mitotic activity [10,54] .…”

“…In addition, given that oxidative stress disrupts the TJ structural complex by modulating the assembly, localization, expression and function of their molecular components [46] , this factor may underlie the altered intestinal TJ expression and increased permeability in obstructive jaundice. The interrelation of oxidative stress with intestinal cellular alterations in extrahepatic cholestasis is also supported by the fact that the oral administration of the antioxidant GSH preserves the intestinal mucosal redox state and prevents intestinal histological and electrophysiological changes [39] . In line with this observation, in a recent work [59] , we demonstrated that administration of different antioxidant substances (N-acetyl-cysteine, allopurinol, α-tocopherol) in ten days' cholestatic rats, induces a significant antioxidant action in the intestine, mediated by a certain influence profile on the thiol redox state by each substance, leading to improvement of intestinal bar rier function and prevention of endotoxemia.…”

Protective effect of the aqueous extract from the root ofPlatycodon grandiflorumon cholestasis-induced hepatic injury in mice

“…In the early stage of BDL, increased activities of serum enzyme levels of ALP and ALT following hepatocyte injury were shown. In addition, even 8 h after BDL, the liver presented clusters of injured hepatocytes and initiation of cholangiocellular proliferation in the large bile duct (Georgiev et al, 2008;Portincasa et al, 2007). In the present study, levels of serum liver enzymes in the BDL alone group were significantly increased by BDL in comparison with the sham-operated group, and these elevated enzyme levels were decreased by pretreatment of BC703.…”

Melatonin Ameliorates Bile Duct Ligation-Induced Systemic Oxidative Stress and Spatial Memory Deficits in Developing Rats

“…Cholestasis is now recognized as a disorder characterized by liver oxidants overload (1)(2)(3). Furthermore, the oxidative stress in cholestatic liver disease is a systemic phenomenon (4,5), probably encompassing all tissues and organs, even those separated by the blood-brain barrier (6).…”