Bilirubin conjugate is a stable, water-soluble ditaurate derivative of bilirubin meant to mimic endogenous bilirubin glucuronide derivatives. In vivo, bilirubin circulates in the plasma and is taken up by hepatocytes and conjugated to one or two glucuronic acids in a reaction catalyzed by UDP glucuronidase to form bilirubin mono or diglucuronide. This water-soluble form is then excreted from the liver in bile in the feces or is converted to urobilinogen and excreted in the urine. In addition to aiding in the disposal of heme, bilirubin and its conjugated derivatives have been shown to exhibit anti-oxidant and antimutagenic effects and to play a role in gut barrier function.
Nitisinone-13C6is intended for use as an internal standard for the quantification of nitisinone by GC- or LC-MS. Nitisinone is an inhibitor of 4-hydroxyphenylpyruvate dioxygenase (HPPD), which converts 4-hydroxyphenylpyruvate (HPPA) to homogentisate in the tyrosine catabolic pathway.1Nitisinone increases urinary levels of HPPA and 4-hydroxyphenyllactate (HPLA) in rats when administered at a dose of 10 mg kg. Nitisinone (3 mg kg) prevents the neonatal lethality of fumarylacetoacetate hydrolase (FAH) deficiency in mice when administered to pregnant dams.2It exhibits hepatoprotective effects inFAH- -mice, such as prevention of increases in plasma levels of aspartate serine aminotransferase (AST) and conjugated bilirubin, when administration is continued following birth at a dose of 1 mg kg. Nitisinone (100 μg) decreases urinary excretion of homogentisate and increases urinary excretion of HPPA, HPLA, and 4-hydroxyphenylacetate in a mouse model of alkaptonuria induced by ethylnitrosourea.3Formulations containing nitisinone have been used in the treatment of hereditary tyrosinemia type 1 (HT-1). 1.Ellis, M.K., Whitfield, A.C., Gowans, L.A., et al.Inhibition of 4-hydroxyphenylpyruvate dioxygenase by 2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione and 2-(2-chloro-4-methanesulfonylbenzoyl)-cyclohexane-1,3-dioneToxicol. Appl. Pharmacol.133(1)12-19(1995) 2.Grompe, M., Lindstedt, S., al-Dhalimy, M., et al.Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type INat. Genet.10(4)453-460(1995) 3.Suzuki, Y., Oda, K., Yoshikawa, Y., et al.A novel therapeutic trial of homogentisic aciduria in a murine model of alkaptonuriaJ. Hum. Genet.44(2)79-84(1999)
Gastrin-releasing peptide (GRP) is a neuropeptide that stimulates gastrin release. It binds to (Ki = 300 nM) and stimulates amylase secretion in rat pancreatic AR42J cells (EC50 = 0.3 nM). GRP increases proliferation of human liver carcinoma HepG2 and MHCC97H cells but does not affect the proliferation of normal HL-7702 liver cells at a concentration of 1 nM. In vivo, GRP (0.35 nmol/kg/h) increases both pancreatic exocrine secretion and pancreatic polypeptide (PP) release in rats. It dose-dependently stimulates gastrin, pancreatic amylase, lipase, bilirubin, and acid output and induces gallbladder contraction in humans when administered at doses ranging from 1 to 27 pmol/kg per hour.
6-Hydroxy Etodolac, a metabolite of the non-steroidal anti-inflammatory drug (NSAID) and COX inhibitor etodolac, causes false positives in diazo diagnostic tests for urinary bilirubin.