On the defensive action of glutamate against the cytotoxicity and fibrogenicity of quartz dust.

Abstract

The cytotoxic action of quartz (DQ12) particles on cultures of rat peritoneal macrophages, as estimated by the inhibition of the TTC-reductase activity, is considerably reduced by preincubation with glutamic acid and by adding sodium glutamate (15 mg/ml) to the drinking water of the rats donating the macrophages. This increase in macrophage resistance under the influence of glutamate is the most probable cause of the delay in the development of silicotic fibrosis shown in several experiments on rats intratracheally injected with quartz and then treated by prolonged administration of glutamate. This effect is probably connected with the influence of glutamate on the stability of the macrophage membranes, which can in its turn be explained by different mechanisms, including the influence on the synthesis and phosphorylation of adenosine nucleotides. Such an influence was shown in rats receiving glutamate by the change of the ATP/ADP ratio in macrophages, but not in erythrocytes. The resistance of rat erythrocytes to the haemolytic action of quartz is also not influenced by the action of glutamate neither in vitro nor in vivo. Such differences in the influences of glutamate on two types ofcells, equally susceptible to quartz cytotoxicity but considerably differing in the character of energy metabolism, is an indirect proof of the role of the latter in the realisation of the anticytotoxic, and thereby antifibrogenic, effect of glutamate.It is known that the high fibrogenicity of silica dusts is connected with their high cytotoxicity for macrophages whose breakdown is accompanied by the formation of some factor that stimulates the synthesis of collagen and interferes with the normal interaction between macrophages and fibroblasts that plays an important part in the regulation of fibrogenesis.1-6 It is not by chance that the first encouraging successes in the experimental treatment and prophylaxis of silicosis were obtained 20 years ago with polyvinylpyridine-N-oxide7-9 and later also with other nitrogen-containing polymer compounds,10-15 whose mechanism of action is connected with the defence of macrophage from the cytotoxicity of silica particles. The key role of this cell in the elimination of dust particles from the alveolar region makes its protection from damage a most important factor in the prophylaxis of silicosis. In fact, polyvinylpyridine-N-oxide stimulates the elimination of quartz dust from the lungs and decreases its retention and penetration.8 9 Nevertheless, the possibilities of the therapeutic, prolonged retention in the organism, and doubts as to their harmlessness. Data on the possible carcinogenic effects of polyvinylpyridine-N-oxidel6 cause some anxiety. Therefore, despite the fact that our laboratory (as seen from the references above) continues the search for highly effective, but less toxic, antisilicotic nitrogen containing polymers, it was but natural to develop research directed at the same link in silicosis pathogenesis but with the use of more physiological means of increasing ...

Subchronic Toxicity of Copper Oxide Nanoparticles and Its Attenuation with the Help of a Combination of Bioprotectors

“…A review of the literature on the mechanisms of toxic and genotoxic action of copper combined with our experience in the testing of various bioprotectors against other intoxications (summarized in [50]) allowed us to choose substances for estimating their possible protective action at subchronic intoxication with nano copper oxide, namely: Glutamate as an effective cell membrane stabilizer through the intensification of ATP synthesis under exposure to the damaging action of various cytotoxic particles (e.g., [7,48,49,50,51] and, at the same time, as one of the three precursors of glutathione, a powerful cell protector against free radicals.The other two precursors of glutathione: Glycine and cysteine (the latter in a highly active and metabolically well available form of N -acetylcysteine).Other components of the organism’s anti-oxidant system (vitamins А, Е, and С, and selenium).Trace elements, which are physiological antagonists of copper (zink, iron, molybdenum, manganese).ω-3 polyunsaturated fatty acids, whose intracellular derivatives are eicosanoids that activate DNA replication and thus play an important part in its repair, which was demonstrated by us earlier under exposure to various genotoxic agents (e.g., [7,51])Pectin enterosorbent as an agent that prevents the re-absorption of the metal excreted into the intestines with bile. …”

Some aspects of the problem of individual predisposition to silicosis.

“…The most striking is a favorable effect of glutamate (18,19,76). Previous experiments have demonstrated the beneficial influence of a balanced diet and the unfavorable effects of excessive protein or particularly, fat (77).…”

Trends and Perspectives of the Biological Prophylaxis of Silicosis

“…As experimental results demonstrating this protective action and substantiating certain hypotheses concerning its mechanisms were published in English and German (48)(49)(50) and thus are easily accessible to western scientists, we shall confine ourselves to an illustration of some results of one of many experiments that had been conducted to estimate that action (Table 4).…”