Studies on nicotinic acid interaction with bilirubin metabolism

Abstract

The mechanism by which intravenous administration of nicotinic acid (NA) increases serum unconjugated bilirubin in patients with the Gilbert's syndrome has been investigated. Studies using the technique of percutaneous transhepatic catheterization of the splenic vein and coil planet centrifuge suggested that following intravenous injection of NA some of the circulating erythrocytes were rendered osmotically fragile and trapped by the spleen and that unconjugated bilirubin increased in the splenic vein blood. In patients with liver cirrhosis, the increments of unconjugated bilirubin were closely correlated with the weights of the spleens removed for the management of varices. In rats, intravenous NA injection enhanced heme oxygenase activities in the spleen, but not uridine-5'-diphosphate (UDP)-glucuronyltransferase activity in the liver. These results are consistent with the hypothesis that NA-induced unconjugated hyperbilirubinemia is a result of complex reactions which include increased erythrocyte fragility, increased splenic heme oxygenase activity, and increased formation of bilirubin in the spleen.

Niacin Inhibits Vascular Inflammation via the Induction of Heme Oxygenase-1

“…For example, HO-1 activity in liver and spleen is rapidly increased in rats after intraperitoneal injection of niacin. 22,23 Dietary supplementation with niacin also increases hepatic HO-1 mRNA levels in rats. 30 In humans, long-term oral administration of niacin at pharmacological doses increases serum bilirubin levels by Ϸ9%.…”

“…15 Intravenous and long-term oral administration of niacin elevates serum bilirubin levels 19 -21 by complex mechanisms that include increased splenic and hepatic HO-I activity. 22,23 Given that bilirubin has known cardioprotective effects, we hypothesized that its formation downstream of HO-1 induction by niacin may explain some of the lipid-independent cardioprotective properties of the drug.…”

Bilirubin Metabolism and its Disorders

“…350 Consistent with this, splenectomy prevents nicotinic acid-induced unconjugated hyperbilirubinemia. 351 Although nicotinic acid administration has also been proposed as a provocative test for the diagnosis of Gilbert syndrome, 351,352 like fasting, it does not clearly separate patients with Gilbert syndrome from normal subjects or those with hepatobiliary disease.…”

Familial Unconjugated Hyperbilirubinemia Syndromes

“…Bilirubin glucuronyl transferase activity is not affected in rats. 77 In the series of Ohkubo et the test reliably differentiated Gilbert's syndrome from chronic liver disease. but not from hemolytic anemia.…”

“…An icterogenic response to nicotinic acid has been long recognized and was originally proposed as a provocative test for Gilbert's syndrome by Fromke and Miller.49 The mechanism of action of nicotinic acid has recently been elucidated by Ohkubo et al 77 Nicotinic acid increases the osmotic fragility of human erythrocytes, leading to increased sequestration in the spleen. In rats it induces splenic, but not hepatic, heme oxygenase, in line with the notion that the source of the increased heme load is erythrogenic.…”