Tag Archives: CYP2E1

Cytochrome P450 2E1 participation in the pathogenesis of experimental metabolic syndrome in guinea pigs

V. V. Rushchak, M. O. Chashchyn

Institute of Molecular Biology and Genetics, National Academy
of Sciences of Ukraine, Kyiv;
e-mail: v.v.rushchak@gmail.com

In this work the experimental metabolic syndrome on the basis of protamine sulfate modeling in guinea pigs was reproduced and pathological processes in the liver of experimental animals were studied. We determined the level of free radicals and markers of liver damage in the blood of experimental animals. We investigated the liver glycogen content and K+,Na+-ATPase activity in the liver of experimental animals as well as measured the cytochrome P450 2E1 (CYP2E1) expression – one of the main factors of oxidative stress. Evidence of development of hepatotoxic processes, increasing of the CYP2E1 level as well as of the free radical level in the animals with metabolic syndrome were found. Using of CYP2E1 inhibitors had shown that the free radical level in the blood of experimental animals depended on the level of the enzyme expression and activity. The obtained results suggest that the changes in the CYP2E1 expression play an important role in the development of hepatotoxic processes upon experimental metabolic syndrome. It was assumed that pharmacological correction of the enzyme expression may be an important mechanism for the influence on the metabolic syndrome clinical course.

Mechanism of hepatoprotective action of methionine and composition “Metovitan” against a background of antituberculosis drugs administration to rats

S. I. Anisimova1, G. V. Donchenko2, Yu. M. Parkhomenko2, V. M. Kovalenko1

1SI Institute of Pharmacology and Toxicology, National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: kovalenko_toxy@yahoo.com

Oral administration of antituberculosis drugs to rats for 60 days in doses that are equivalent to clinical ones, causes changes in mRNA levels expression of liver cytochrome P-450 isoforms CYP3A2, CYP2C23, CYP2E1 and pro- and antioxidant state. Experimental composition “Metovitan” given with anti-TB drugs provided a correction of these abnormalities, that is evidenced by modulation of the level of CYP3A2, CYP2C23, CYP2E1 gene expression and antioxidant activity, inhibition of lipid peroxidation. “Metovitan” normalizes the enzymatic activity and content of total billirubin in the blood serum, shows high hepatoprotective properties, exceeding the efficiency of methionine.