Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease

Background-There is considerable evidence indicating that the severity of h epatic damage in individuals with cholestatic liver disease is causally ass ociated with the extent of intrahepatic oxidative stress. Increased levels or accelerated generation of reactive oxygen species and toxic degradative products of lipid peroxidation have been reported in the plasma of individu als with chronic liver disease and animal models of liver disease. Hence, b y virtue of their increased presence in the circulation, it is not unreason able to suppose that they may account for extrahepatic tissue damage in chr onic Liver disease. Materials and methods-This hypothesis was tested by determining plasma leve ls of the ubiquitous antioxidant glutathione (GSH) and lipid peroxides (LP) , together with assessment of the extent of lipid peroxidation in the kidne y, brain, and heart, in 24 day chronically bile duct ligated (CBDL) rats. T he extent of lipid peroxidation in tissues was based on measurement of conj ugated dienes, lipid peroxides, and malondialdehyde (MDA) content. Data wer e compared with identical data collected from unoperated control, pair fed, 24 day bile duct manipulated (sham operated), and pair fed sham operated r ats. Results-In CBDL rats, total and reduced plasma GSH levels were almost half those determined in all control rats. Plasma, kidney, and heart LP levels w ere significantly increased in CBDL rats compared with controls. MDA levels were significantly higher in the kidney, brain, and heart homogenates prep ared from CBDL rats compared with MDA content measured in tissue homogenate s prepared from the four groups of control rats. Conclusions-Our data show that experimental cholestatic liver disease is as sociated with increased lipid peroxidation in the kidney, brain, and heart. Hence we have concluded that the oxidative stress in cholestatic liver dis ease is a systemic phenomenon probably encompassing all tissues and organs, even those separated by the blood-brain barrier.