A new immobilized cell system with protection against toxic solvents

A new immobilized cell system providing protection against toxic solvents was investigated so that normal fermentations could be carried out in a medium containing toxic solvents. The system consists of immobilized growing cells in Ca-alginate gel beads to which vegetable oils, which are inexpensive absorbents of solvents, had been added. The ethanol fermentation of Saccharomyces cerevisiae ATCC 26603 was used as a model fermentation to study the protection afforded by the system against solvent toxicities. The fermentation was inhibited by solvents such as 2-octanol, benzene, toluene, and phenol. Ethanol production of one batch was not finished even after 35 h using immobilized growing yeast cells in conventional Ca-alginate gel beads in an ethanol production medium (5% glucose) containing 0.1% 2-octanol, which is used as a solvent for liquid-liquid extraction and is one of the most toxic solvents in our experiments. With the new immobilized growing cell system using vegetable oils, however, four repeated batch fermentations were completed in 35 h. Castor oil provided even more protection than soy bean, olive, and tung oils, and it was possible to complete six repeated batches in 35 h. The immobilized cell system with vegetable oils also provided protection against other toxic solvents such as benzene and toluene. A possible mechanism for the protective function of the new immobilized cell system is discussed.     

Intestinal microflora in rats under the conditions of a chronic toxic lesion of the liver

Intestinal microflora in healthy rats and its changes under the conditions of experimental chronic toxic hepatitis were studied. The study revealed that in intact animals the microflora of the small intestine was represented by bacteria of the genera Escherichia, Enterobacter, Moraxella, Alcaligenes, Staphylococcus, Streptococcus. Bacteria of the genera Escherichia, Enterobacter, Moraxella, Alcaligenes, Staphylococcus, Corynebacterium and Clostridium were isolated from the large intestine. No bacteria were found in the systemic blood, the contents of the portal vein, as well as in the liver parenchyma and the mesenterial lymph nodes. As the result of dysbiosis induced by the introduction of kanamycin and in chronic hepatitis caused by carbon tetrachloride the sharp decrease in the species composition of microbial communities (up to 2-3 species) in the small intestine and was observed along with penetration of bacteria into the blood stream, the mesenterial lymph nodes and the liver parenchyma. The tendency towards the restoration of the quantitative and qualitative microflora composition was noted following administration into experimental animals of bactisubtil and amixin--an inductor of interferonogenesis.     

Humoral factors in the regulation of the natural resistance of the body in toxic lesion of the liver]

The dynamics of natural resistance factors (complement, lysozyme, the bactericidal potency of blood serum) were found to be similar in rabbits with the toxic lesions of the liver resulting from the administration of carbon tetrachloride and in intact homologous rescipients receiving the serum of poisoned animals. Simultaneously a decrease in the complement titre and an increase in lysozyme activity and in the bactericidal potency of blood serum were observed. The effect thus revealed could be suppressed by treating the serum with contrical, a polyvalent proteinase inhibitor.     

The capacity of glutathione reductase in cell protection from the toxic effect of heated oils

This empirical study tries to focus on the evidence that the wrong use of oil in food cooking leads to health problems. High temperatures associated with the repeated use of the same oil lead to the breakdown of some fatty acids, forming numerous toxic polymer compounds and peroxides. The obtained data have showed that the ratios of polymer compounds reached 11.3% in oil heated continuously for 10 h at 220 degrees C, and 37.8% in frying oil (FO). Moreover, the polar compound ratios reached 25.6% and 47.6% in continuously heated oil (CHO) and FO, respectively. However, the peroxide concentrations were 157.1 and 133.6 mM/kg in CHOs and FOs, respectively. The observed results have allowed the study of the role of the glutathione redox system in the detoxification and elimination of different toxic peroxides resulting from heated oils. On a diet of 10% of CHO and FO, a significant increase in glutathione peroxidase (GPx) and glutathione reductase (GR) activities appears. This combined relationship between the decreased glutathione content and the increased GPx and GR activities in rats fed on CHO and FO confirms the participation of the glutathione redox system in the detoxifying reactions of continuously accumulated peroxides.     

Action of streptokinase on the hemostatic indices of rabbits with a toxic lesion of the liver due to carbon tetrachloride

The rabbits with CCl4-induced hepatic failure have revealed changes in hemostasis responses to streptokinase administration. The main distinction of hepatic dystrophy was the depression of plasma fibrinolytic activity accompanying the decrease in fibrinogen and antiplasmin concentrations. Streptokinase administration to rabbits with productive inflammatory liver disorders produced changes in hemostasis identical to those observed in intact rabbits, fibrinogen levels, however, remained unchanged. The common feature of all the toxic liver disorders is the increase of antithrombin III levels after streptokinase administration, whereas the antithrombin levels in the control animals were decreased.     

Ultrastructure of the "dark" hepatocytes under physiologically normal conditions and in toxic lesion of the liver (a morphometric study)]

Quanity and structural organization of the "dark" hepatocytes are different depending on the functional state of the liver. Therefore, functional estimation of the liver state with a changed number of "dark" hepatocytes demands detection of factors determining the changes in their organization and quantity in the organ.     

Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury

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Liver cell hydration

Liver cells possess potent mechanisms to maintain their volume, i.e., their hydration state. These volume-regulatory mechanisms, however, are apparently not designed to maintain absolute cell volume constancy; they rather act as dampeners to prevent excessive cell volume deviations, which would otherwise result from cumulative substrate uptake or anisotonic stress. Furthermore, these volume-regulatory mechanisms can even be activated in the resting state by hormones and other stimuli, and by that means cell volume changes are affected secondarily. Thus, liver cell hydration can change within minutes under the influence of aniso-osmolarity, hormones, nutrients, and oxidative stress. Such short-term modulation of cell volume within a narrow range acts as an independent and potent signal which modifies hepatocellular metabolism and gene expression. Accordingly, cell volume homeostasis involves the integration of events that allow cell hydration to play a physiologic role as a regulator of cell function.     

Effect of chitosan on lipid peroxidation in toxic liver injury

Lipid peroxidation was intensified by tetrachloromethane in liver. Concentration of lipid peroxidation products was decreased after chitosan injections. It was shown that application of chitosan had a positive effect on the liver of mice intoxicated by tetrachloromethane.     

Spontaneous reversibility of advanced toxic liver cirrhosis.

The spontaneous restoration of liver cirrhosis induced by 6 and 9 month CC14 treatment has been studied. The OH-proline content of the liver stroma, the DNA content of the parenchyma, and the Co/DNA ratio were determined. Observations lasted for 4 months after completion of treatment. Cirrhosis developed after 6 month, CC14 administration was reversible in 3--4 months after the discontinuation of treatment; the normal stroma parenchyma ration had gradually normalized. Nine month treatment exhausted the capacity of the stroma for spontaneous recovery and the parenchyma regenerated to a lesser extent. Fibrosis remained practically irreversible 4 months after CC14 administration.     

Expression of rat liver glutathione-S-transferase GSTA5 in cell lines provides increased resistance to alkylating agents and toxic aldehydes

The glutathione-S-transferases (GST) are a major contributor to the eukaryotic cell's defences against chemical and oxidative stress. However, the role of individual GST isoenzymes in conferring resistance to xenobiotics has not been fully determined. We have examined the effect of the rat GSTA5 isoenzyme in the detoxication of alkylating agents and aldehydes by constructing a cell line in which it is stably expressed. The hamster fibroblast cell line V79 was transfected with a construct expressing GSTA5 from the CMV promoter. A stable clone (V79-GSTA5) was isolated after selecting for the neomycin phosphotransferase gene present on the introduced DNA. The cell line showed significantly increased levels of resistance towards the alkylating agents chorambucil and melphalan. Levels of resistance were 4-6-fold greater in V79-GSTA5 cells than in control cells. Increased levels of resistance were also observed towards the lipid peroxidation product acrolein (IC(50)=80 microM compared with 17 microM in control cells). The V79-GSTA5 cells also showed a 4-fold increase in resistance to trans, trans muconaldehyde (IC(50)=4 micro compared with l microM for control cells). GSTA5 did not protect against 4-hydroxynonenal, but it did provide greater levels of protection to hydrogen peroxide, with an IC(50) of 380 microM in V79-GSTA5 compared with 180 microM in control cells. In contrast, V79-GSTA5 cells were more sensitive to methyl glyoxal, suggesting that a methyl glyoxal-glutathione conjugate is more toxic that the parental compound. These data contribute towards the evaluation of the role of GSTA5 in the detoxication of these compounds.