Localization of uridine 5′-diphosphate-glucuronosyltransferase in human liver injury

doi:10.1016/0016-5085(95)90695-9

Gastroenterology

Volume 108, Issue 5, May 1995, Pages 1464-1469

https://doi.org/10.1016/0016-5085(95)90695-9 Get rights and content

Abstract

$Background/Aims$ Pharmacokinetic studies in patients with cirrhosis have shown a decreased clearance of drugs metabolized by cytochrome P450, whereas drugs metabolized by glucuronidation frequently have a normal elimination. The mechanism for the apparent preservation of glucuronidation has not been elucidated. The aim of this study was to examine the expression of uridine 5′-diphosphate-glucuronosyltransferase (UGT) in human liver injuries. $Methods$ UGT was measured by immunohistochemistry using a UGT polyclonal antibody, which was then compared with a representative isoform of cytochrome P450. Normal liver biopsy specimens (n = 8) and a spectrum of liver injury biopsy specimens (n = 47) were examined. $Results$ Compared with normal liver, increased staining for UGT in remaining hepatocytes was seen in liver damaged by chronic alcohol abuse, but the most intense immunoreactivity was observed in remaining and regenerative hepatocytes in specimens with cirrhosis. Primary biliary cirrhosis showed diffusely increased immunoreactivity. Other nonmalignant groups showed an increased staining relative to chronicity of liver disease. In contrast, in all liver injuries, cytochrome P450 staining was reduced as compared with controls. $Conclusions$ Chronic liver damage results in increased UGT in remaining viable hepatocytes. Mechanisms may operate in liver injury to preserve expression of UGT in functional hepatocytes, and this may explain the preservation of glucuronidation in cirrhosis.

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Localization of uridine 5′-diphosphate-glucuronosyltransferase in human liver injury

Abstract

Gastroenterology

J Biol Chem

Biochem Biophys Res Commun

Biochem Biophys Res Commun

Gastroenterology

Gastroenterology

Pharmacol Ther

Is glucuronidation truly preserved in patients with liver disease?

Hepatology

Release of latent glucuronosyltransferase activity contributes to the sparing of glucuronidation in experimental liver injuries

J Gastroenterol Hepatol

Normal disposition of oxazepam in acute viral hepatitis and cirrhosis

Ann Intern Med

The effects of aging and liver disease on the disposition of lorazepam in man

Clin Pharmacol Ther

Temazepam clearance is unaltered in cirrhosis

Am J Gastroenterol

Flavin containing monooxygenase activity in human liver microsomes

Drug Metab Dispos

The unlabelled antibody enzyme method of immunohistochemistry

Immunohistochemical localization of parathyroid hormone-related protein in parathyroid adenoma and hyperplasia

J Pathol

Immunohistochemical localization of parathyroid hormone-related protein in human breast cancer

Cancer Res

The effects of age and liver disease on the disposition and elimination of diazepam in adult man

J Clin Invest

The effect of cirrhosis in the disposition and elimination of meperidine on man

Clin Pharmacol Ther