Bilirubin Oxidation Provoked by Endotoxins Treatment is Suppressed by Feeding Ascorbic Acid in a Rat Mutant Unable to Synthesize Ascorbic Acid

Abstract

We examined the possibility that bilirubin oxidation is provoked in vivo by using scurvy-prone ODSodlod rats treated with endotoxin (lipopolysaccharide). Recently, bilirubin oxidative metabolites were isolated from human urine and named biotripyrrin-a and biotripyrrin-b. In ODs-odlod rats fed an ascorbicacid-free diet, the concentration of bilirubin metabolites in urine was increased 7.0-fold at 3 h after injection of lipopolysaccharide and 4.4-fold at 10 h compared to the control rats injected with saline. The dietary supplement of ascorbic acid, the physiological antioxidant, suppressed the increase in bilirubin metabolites in urine after lipopolysaccharide injection : concentrations of biotripyrrin-a and biotripyrrin-b in urine collected 6.5-10 h after the injection were lower in rats fed an ascorbic-acid-supplemented diet than in rats fed an ascorbic-acid-free diet. Moreover, feeding of ascorbic acid suppressed the hepatic mRNA level of heme oxygenase-1, the rate-limiting enzyme of bilirubin biosynthesis, in rats injected with lipopolysaccharide. These findings indicate that bilirubin oxidation is markedly stimulated in lipopolysaccharide-treated rats and suggest that bilirubin and ascorbic acid have physiologically protective effects against oxidative stress.

Ascorbic Acid Deficiency Stimulates Hepatic Expression of Inflammatory Chemokine, Cytokine-Induced Neutrophil Chemoattractant-1, in Scurvy-Prone ODS Rats

“…It is known that reactive oxygen intermediates are second messengers in the activation of NF-B ( 21 ) and included in the stimulation of inflammatory cytokine gene expressions. Ascorbic acid has a capacity to scavenge reactive oxygen intermediates, and is a physiological compound exhibiting this capacity ( 22 ). In the liver of ascorbic acid-deficient ODS rats, it is speculated that the increase in the amount of reactive oxygen intermediates might cause the activation of NF-B, leading to the stimulation of CINC-1 gene expression.…”

Biphasic Elevation of Bilirubin Oxidation During Myocardial Ischemia Reperfusion

“…Conceivable explanations for the early elevation of urinary biopyrrin level could be serum bilirubin oxidation or increased hemolysis during the inflammatory process after MIR. Yamaguchi et al found that increased bilirubin oxidation precedes HO-1 upregulation in a lipopolysaccharide-treated rat model 36 and Morita et al discovered that serum bilirubin levels significantly decrease after the spasm provocation test in patients with ischemic heart disease. 33 Those reports support the notion that biopyrrins are synthesized as a result of serum bilirubin oxidation.…”

“…30,31 Biopyrrins are immediately excreted in urine because of their hydrophilic properties and thus can reflect the severity of oxidative stress. 25,[32][33][34][35][36][37][38] Biopyrrin synthesis reflects NO radicals, 25 so urinary biopyrrin levels can indicate ongoing changes in oxidative stress in vivo and thus function as a marker of oxidative stress.The time course of urinary and tissue biopyrrin levels in rat models of cardiac transplantation and hepatic ischemia reperfusion has been investigated. 25,32 A cardiac transplantation study showed that levels of urinary biopyrrins become more rapidly and sensitively elevated than either urinary 8-hydroxy-2'-deoxyguanosine or serum troponin-T during …”

“…30,31 Biopyrrins are immediately excreted in urine because of their hydrophilic properties and thus can reflect the severity of oxidative stress. 25,[32][33][34][35][36][37][38] Biopyrrin synthesis reflects NO radicals, 25 so urinary biopyrrin levels can indicate ongoing changes in oxidative stress in vivo and thus function as a marker of oxidative stress.…”

Promotive Effects of the Dietary Organic Germanium Poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) on the Secretion and Antioxidative Activity of Bile in Rodents

“…Moreover, bilirubin has anti-oxidative effects. 12,13) The increasing levels of fecal pigment seen after Ge-132 ingestion suggest the enhancement of bilirubin excretion in the intestine. In this study, we first compared the color of the cecal pigment of rats.…”