Comparative characteristic of serpin--alpha-1 proteinase inhibitor in human and mice serum

Serpin alpha-1-proteinase inhibitor have been studied in human subjects and in mice of different lines as acute phase reactant and during tumor development. In humans, there was no difference of serpin activity between men and women. Increased activity was noted in men with acute trauma (acute phase reaction). Comparatively to male, in female mice of different lines decreased activity of serum alpha-1-proteinase inhibitor, was shown. There was no increase of alpha-1-proteinase inhibitor activity during inflammation induced by zymosan administration in mice. alpha-1-proteinase inhibitor belongs to acute phase reactants in humans but not in mice; for mice alpha-2-macroglobulin is a more typical acute phase reactant as compared to alpha-1-proteinase inhibitor. Murine tumor development (hepatoma HA-1, lymphosarcoma LS, Lewis lung adenocarcinoma) was followed by a decreased activity of serum alpha-1-proteinase inhibitor both in successfully treated and untreated groups. According to data of literature, similar dated were obtained in humans with tumors. It was suggested that changes of expressiln of alpha-1-proteinase inhibitor by tumors and its secretion were involved in decreased activity of alpha-1-proteinase inhibitor.     

The effect of changes in CYP2E1 activity in the liver on toxicity and carcinogenicity of diethylnitrosamine in mice

In this work, the biological effects of diethylnitrosamine (DENA) have been studied under controlled conditions of its metabolism in mice of different ages. The results indicate that the general toxic and hepatocarcinogenic effects of DENA are mostly due to the parent compound, whereas the alkylating metabolites cause hepatic cell damage. Our findings cast doubt on the conventional understanding of the exclusive role of mutagenic activation in the carcinogenic action of chemicals.     

Age- and sex-related differences in sensitivity to hepatotoxic action of estragole in mice

As determined by blood activity of alanine- and aspartate aminotransferases, intraperitoneal injection of estragole in subcarcinogenic dose 300 mg/kg does not damage the liver of suckling off-spring of both sexes and of adult SWR/J males but drastically damages it in mature females of this strain. Castration only slightly decreases the resistance of males to hepatotoxic action of estragole but significantly increases it in females; exogenous administration of estradiole benzoate to castrated males decreases their resistance to the hepatotoxin, whereas administration of testosterone propionate to ovariectomyzed females does not elevate it. Morphologically, estragole damages the same number of liver cells in females and males, but in males it induces mostly hydropic degenerative, and in females--necrotic changes of hepatocytes.