Ursodeoxycholic acid in primary biliary cirrhosis improves glutathione status but fails to reduce lipid peroxidation.
BACKGROUND
Ursodeoxycholic acid (UDCA) may slow progression in primary biliary cirrhosis (PBC), but its effect on survival is controversial. We have previously demonstrated that oxidant stress, with severely depressed plasma glutathione, is a feature of untreated PBC; this study examines the effect of UDCA on lipid peroxidation, antioxidant status and associated processes.


METHODS
Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis, inflammation, cholestasis and synthetic function were measured at 0, 3, 6, 9 and 12 months in blood and urine from 35 PBC patients receiving UDCA.


RESULTS
Plasma glutathione, reflecting intrahepatic levels, climbed steadily on UDCA; although still subnormal, the median value at 12 months was 2.4-fold higher than the untreated level. Liver enzyme markers and C-reactive protein also improved, whilst PIIINP improved steadily, but the change did not attain statistical significance. Serum bilirubin remained unchanged and total antioxidant capacity, albumin and vitamin E decreased after 12 months' UDCA treatment. 8-Isoprostane increased and malondialdehyde was unchanged.


CONCLUSIONS
UDCA treatment partially corrected plasma glutathione status and some other biomarkers greatly improved, but lipid peroxidation was not reduced. UDCA may, therefore, require supplementation with glutathione precursors and/or antioxidant cocktails to reduce oxidant stress and thus delay disease progression to cirrhosis.
Pemberton
Philip W
PW
The Liver Unit, Manchester Royal Infirmary, Manchester, UK.
Aboutwerat
Ali
A
Smith
Alexander
A
Warnes
Thomas W
TW
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D005978:Glutathione / Q000097:blood* / Q000737:chemistry*; D006801:Humans; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014580:Ursodeoxycholic Acid / Q000097:blood / Q000737:chemistry / Q000502:physiology*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000975:Antioxidants; C075750:8-epi-prostaglandin F2alpha; D014580:Ursodeoxycholic Acid; D015237:Dinoprost; D005723:gamma-Glutamyltransferase; D005978:Glutathione