NCX 1000

Animal experiment:

Rats: On the first protocol, 54 rats, 12 animals/group unless specified, are randomly allocated to receive one of the following treatments: group 1 has phenobarbital induction and no further treatment; group 2 (16 animals) is treated with CCl4 twice a week for 8 weeks; group 3 has CCl4 twice a week plus UDCA (15 mg/kg); and group 4 has CCl4 twice a week plus NCX-1000 (15 mg/kg). NCX-1000 and UDCA are dissolved in carboxymethyl cellulose and administered daily by gavage. Animal weight is monitored daily through the study period, and the dosage of CCl4 is adjusted accordingly to the animal weight. At the end of the treatment surviving animals are killed by an overdose of uretane, and blood, ascitic fluid, and livers are collected. A portion of each liver is fixed in 10% formalin for histological evaluation. The remaining tissue is partitioned and immediately stored under frozen liquid nitrogen at -80°C until used. On the second protocol, 74 rats are randomly allocated to receive the same treatments as protocol 1. At the end of the study, surviving animals are tested for portal and arterial pressure measurement.

References:

[1]. Fiorucci S, et al. NCX-1000, a NO-releasing derivative of ursodeoxycholic acid, selectively delivers NO to the liver and protects against development of portal hypertension. Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8897-902. Epub 2001 Jul 10.
[2]. Fiorucci S, et al. NCX-1000, a nitric oxide-releasing derivative of ursodeoxycholic acid, ameliorates portal hypertension and lowers norepinephrine-induced intrahepatic resistance in the isolated and perfused rat liver. J Hepatol. 2003 Dec;39(6):932-9.