Bilirubin elimination

B8 Beck, K. and Falk, H. Influence of different compounds on glucuronide synthesis and bilirubin elimination. Liver Research, J. Vandenbroucke, Tijdschrift voor Gastroenterolo-gie, Antwerpen, 1967... 

Bilirubin [635-65-4] M 584.7, e450nm t OO in CHCI3, pKE t 3 0. An acyclic tetrapyrrole bile pigment with impurities which can be eliminated by successive Soxhiet extraction with diethyl ether and MeOH. It crystallises from CHCI3 as deep red-brown rhombs, plates or prisms, and is dried to constant weight at 80 under vacuum, [Gray et al. J Chem Soc 2264, 2276 1961.]... 

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Bilirubin is eliminated by dializing the incubated /Miitrophenolate ion (at pH 10.5, and maintaining at 38°C for 30 minutes) into 2-amino-2-methyl-l-propanol, without carrying out the blank determination stated... 

Bilirubin is the waste product derived from haem catabolism. In order to be eliminated from the body, mainly via the gut, bilirubin must be processed through the liver (see Section 6.4). Bilirubin is, however, insoluble in water, so to reach the liver from the spleen where a substantial amount of red cell destruction occurs, bilirubin must first be bound to albumin. As blood perfuses the liver, bilirubin is transported into the hepatocyte where it is conjugated with glucuronic acid prior to excretion. 

In most normal adult animals, conjugation of bilirubin with various sugars probably represents the major mechanism for its transformation (Fig. 1). The reaction products are eliminated from the organism by excretion into the bile. Glucuronyl transfer has been investigated in... 

The liver is the principal metabolic organ, and hepatic disease or dysfunction may impair drug elimination. Any alteration in the serum albumin or bilirubin levels and in the prothrombin time indicates impaired liver function. Similarly, skin bruising and bleeding tendency indicate decreased production of clotting factors by the liver. 

A modification of Powell s method (P4), with sodium benzoate and urea solution to speed up the coupling reaction, has been used by O Hagan (01) to investigate the bilirubin content of serum from a large number of blood donors. He stated that color development was maximal in half a minute and that errors due to hemoglobin and ferrihemalbumin could be eliminated by the use of suitable blanks. The mean values for serum bilirubin in 200 donors were 0.45 0.19 mg/100 ml serum for males and 0.36 0.18 mg/100 ml serum for females. Of 2500 people screened, only 108 had unaccountably high levels of over 1.5 mg j0, and this level was arbitrarily taken as the upper limit of normal. 

Sims and Horn (S13) did not consider that the addition of urea to the sodium benzoate solution was of any advantage and observed speedy coupling at pH 6.0-7.0 without it. The addition of nitrite to the diazo blank was found to eliminate errors due to hemolysis, and colorimetric readings were made at 525 mp since this is the isobestic wavelength for oxyhemoglobin and methemoglobin. Urea-ethanol solution has also been used to facilitate rapid coupling of bilirubin with diazotized sulfanilic acid. Patterson et al. (PI) have been able to eliminate the cloudiness that tends to develop with this method by the addition of concentrated phenol. 

Artificial liver support systems aim at the extracorporeal removal of water soluble and protein-bound toxins (albumin being the preferential binding protein) associated with hepatic failure. Albumin contains reversible binding sites for substances such as fatty acids, hormones, enzymes, dyes, trace metals and drugs [26] and therefore helps elimination by kidneys of substances that are toxic in the unbound state. It should be noticed that the range of substances to be removed is broad and not completely identified. Clinical studies showed that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver. Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile adds, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be benefidal to the dinical course of a patient in liver failure. 

Subsequent studies have shown (e.g. 5,6, Table I) that the liver of newborns is indeed deficient in enzymes needed not only for drug metabolism but also for the elimination of natural products. For example, because of the lack of UDP-glucuronyl transferase resulting in the inability to dispose of bilirubin, the newborn is at risk for brain damage by kernicterus. That PEP carboxykinase, the key catalyst of gluconeogenesis de novo is absent at 7 months and still at low titers 3 days after birth (Table I), probably contributes to the fact that transient hypoglycemia (which can also cause brain damage) represents a hazard to full term as well as premature infants. The immaturity of the hepatic enzyme composition imposes limitations on the choice of nutrients used to supplement or re-... 

Glucuronidation is an important step in the elimination of many important endogenous substances from the body, including bilirubin, bile acids, steroid hormones, thyroid hormones, retinoic acids, and biogenic amines such as serotonin. Many of these compounds are also substrates for sulfonyltransferases (SULTs) (2). 

Wagner M, Halilbasic E, Marschall HU, et al. CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice. Hepatology 2005 42 420-430. 

Metabolism and elimination rates are generally lower in neonates than in adults. The elimination half-lives of substances used as indicators of liver function (e.g. bromosulfthalein, bilirubin), for example, are longer in newborns than in adults. Renal clearance has been shown to be lower in neonates than in older children and adults, for all chemical classes lipophilic, hydrophilic, and organic ions (Clewell et al., 2002). Glomerular filtration rate at normal-term birth is about one third of the adult value when expressed on the basis of body surface area and matures in about six months. On the other hand, the tubular reabsorption process reaches adult levels within a few days after birth. 

Two genetically distinct heme oxygenases (HOs) have been characterized HO-1 is an inducible form, whereas HO-2 is constitutive. HO-2 is abundant in selective tissues such as brain and the cardiovascular system. HO-1 is highly inducible in many tissues in response to a variety of stresses, including infection, exposure to xenobiotics, hypoxia, and proinflammatory cytokines. The recognition that heme oxygenase is expressed in many different tissues led to studies of the role of heme degradation apart from the pathway for formation and elimination of bilirubin derived from destruction of senescent erythrocytes. 

The bilirubin that is produced in phagocytic cells from degradation of hemoglobin represents the majority of the bilirubin that is produced and must be eliminated. This initially requires transport of bilirubin from the phagocytic cells to the liver. Normally, bilirubin is secreted from phagocytic cells and complexed with albumin for transport to the liver. It is essential that bilirubin is transported through the circulation bound to albumin. The toxicity of... 

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