Effect of polysaccharides and human plasma lipoproteins on the secretion of cystatin C by peritoneal macrophages from normal and tumor bearing mice.

Intact peritoneal macrophages in vitro secreted the cysteine proteinase inhibitor cystatin C. Polysaccharides stimulated cystatin C secretion: lipopolysaccharide < carboxymethylated beta-D-glucan < sulfoethylated beta-D-glucan. Human plasma low-density- (LDL) and high-density lipoproteins (HDL) are still more potent inducers of cystatin C secretion by macrophages. Peritoneal macrophages from mice with experimental HA-1 hepatoma compared to those from intact mice secreted more cystatin C with maximum polysaccharide-stimulated secretion after 30 min of incubation. LDL and HDL induced cystatin C secretion by tumor macrophages also.

[Age-related changes in protein and lipid oxidation in the liver of prematurely aging rats OXYS]. / Vozrastnye izmeneniia okislennosti belkov i lipidov v pecheni prezhdevremenno stareiushchikh krys OXYS.

Age-dependent variations in products of lipid peroxidation products (LPO) and oxidative damage of proteins have been studied in the liver mitochondria and microsomes of premature aging OXYS rats. Characteristics of oxidative processes in OXYS rats were compared with parameters in Wistar rats. Changes in lipid peroxidation products content and oxidative damage of proteins in rat liver mitochondria and microsomes of both strains rats were nonlinear and had opposite direction during the first year of life. The level of protein oxidative damage in OXYS rat liver mitochondria and cytosol was higher than in Wistar at 12 months. The content of primary and end lipid peroxidation products in OXYS rat liver microsomes was significantly decreased in 12 months, but content of conjugated dienes was increased in mitochondria.

[Activity and induction of CYP2B, CYP2C, and CYP3A in tissues of cyclophosphane-sensitive and resistant neoplasms and the liver of neoplasm-carrying mice]. / Aktivnost' i indutsiruemost' CYP2B, CYP2C i CYP3A v tkani chuvstvitel'nykh i ustoichivykh k deistviiu tsiklofosfamida opukholei i pecheni myshei-opukholenositelei.

The activities of three cytochrome P450 families involved in metabolic transformation of cyclophosphamide (CP) (CYP2B and CYP2C responsible for metabolic activation of CP and CYP3A responsible for inactivation of CP) have been investigated in lymphosarcoma and liver microsomes of tumor-bearing CBA mice. Two strains of mouse lymphosarcoma distinguished by their sensitivity to cytostatic action of CP were used in this study for implantation in mice femur muscle. There was certain relationship between CP resistance of lymphosarcoma and tumor P450s activity. CYP2B, CYP2C and CYP3A activities in the CP sensitive tumor were comparable to those in liver, and CYP2B, CYP2C were induced by phenobarbital and dexamethasone. CYP2B and CYP2C in the CP resistant tumor were inactive and only slightly induced by dexamethasone. CYP3A activity was lower than in LS tumor and unchanged during drug treatment. Implantation of LS and RLS tumor in mice caused different effects on P450 activities. LS insignificantly influenced liver CYP2B, CYP2C and CYP3A activities and their inducibility by phenobarbital and dexamethasone was similar to that obtained in liver of mice without tumor. At the same time, CYP2B and CYP2C activity in liver of RLS-bearing mice were essentially reduced, the activity CYP3A remained unchanged, and inducibility of CYP2B, CYP2C and CYP3A by phenobarbital and dexamethasone was similar to that in liver of mice without tumor. These results prove the role of cytochromes P450 activating CP in formation drug resistant phenotype of mice lymphosarcoma and suggest possibility of overcoming of this resistance using cytochrome P450 inducers.

[Bilirubin as an endogenous intermediary in the activation of CYP1A1 expression upon exposure to ultrasound]. / Bilirubin kak éndogennyi posrednik v aktivatsii ékspressii CYP1A1 pod deistviem ul'trazvuka.

The induction of cytochrome P4501A1 (CYP1A1) enzyme activity reflects the increased ligand-dependent transcriptional activity of the cognate CYP1A1 gene. The list of ligands includes various xenobotics such as polycyclic and halogenated aromatic hydrocarbons. Until recently, similar role for endogenous compounds was unknown. In the present study the ability of the endogenous heme metabolite, bilirubin, to regulate CYP1A1 activity was examined. The following parameters were investigated: expression of CYP1A1 in rat liver at a level mRNA, protein and functional activity under at the experimental rising of blood bilirubin level. The influence of local ultrasound contact treatment of rats hepatic area in vivo (the intensity 0.4 W/cm2 and duration time of 10 minutes) on blood unconjugated bilirubin concentration and parameters of CYP1A1 transcriptional activity was also investigated. The ultrasound contact action on rat hepatic are increased blood unconjugated bilirubin concentration. The rise of bilirubin levels of in rat blood after intravenous administration of bilirubin as well as after ultrasound treatment was accompanied by increased mRNA CYP1A1, protein and functional activity of CYP1A1. The comparison of these data with that of time-dependent changes of parameters of CYP1A1 transcriptional activity under ultrasound action and experimental rising of blood bilirubin level suggest that induces CYP1A1 and may be an intermediate in the activation of CYP1A1 expression under ultrasound action.