Defective hepatobiliary leukotriene elimination in patients with the Dubin-Johnson syndrome.
The Dubin-Johnson syndrome (DJS) is characterized by a hereditary conjugated hyperbilirubinemia and a typical dark pigment accumulation in liver parenchymal cells. In the present study the renal excretion of leukotrienes in five patients with histologically established DJS and five age- and sex-matched healthy subjects was investigated. Endogenous urinary leukotrienes were separated by high-performance liquid chromatography and subsequently quantified by immunoassays and gas chromatography-mass spectrometry. Patients with DJS excreted significantly (P < 0.01) greater amounts of cysteinyl leukotriene, LTE4 (8-fold), the omega-oxidation product omega-carboxy-LTE4 (15-fold) and the beta-oxidation metabolite omega-carboxy-tetranor-LTE3 (26-fold) into urine than healthy controls. These results imply that in DJS leukotriene elimination into bile is defective, leading to a compensatory renal leukotriene elimination and a typical excretion pattern of urinary leukotriene metabolites. Analysis of endogenous urinary leukotrienes seems to be a new approach to the noninvasive diagnosis of this disease.
Mayatepek
E
E
Department of General Pediatrics, University Children's Hospital, University of Heidelberg, Germany.
Lehmann
W D
WD
D000328:Adult; D000368:Aged; D001652:Bile Ducts / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000652:urine; D005260:Female; D006801:Humans; D007566:Jaundice, Chronic Idiopathic / Q000652:urine*; D007668:Kidney / Q000378:metabolism; D017999:Leukotriene E4 / Q000652:urine*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D017999:Leukotriene E4; D003404:Creatinine