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

Our plain-English summary of On the defensive action of glutamate against the cytotoxicity and fibrogenicity of quartz dust, by K.I. Morosova, G.V. Aronova, B.A. Katsnelson, et al (British Journal of Industrial Medicine, 1982).

The study

• Authors: K.I. Morosova, G.V. Aronova, B.A. Katsnelson, B.T. Velichkovski, A.M. Genkin, L.N. Elnichnykh, L.I. Privalova
• Journal: British Journal of Industrial Medicine
• Published: 1982;39(3):244-52
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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 of cells, 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.

In plain English

This laboratory report summarised the authors' experiments on whether glutamate protects cells and lungs against quartz dust. Rat peritoneal macrophages were exposed to quartz (DQ12) in vitro, damage being measured by inhibition of TTC-reductase activity. In the preincubation series, activity at the 2 mg quartz dose was 83.5% of the activity of cultures acted on by neither glutamate nor quartz after glutamic acid 50 micrograms per millilitre, versus 59.6% in quartz-exposed control cultures. The quartz dose graphically estimated to give 50% inhibition was 2.8 mg for control and 7.2 mg for preincubated cultures, which the authors called a 2.6-fold rise in resistance. Macrophages from rats drinking sodium glutamate (15 mg/ml) for one, two or four months were also significantly more resistant than those from water-drinking rats. Glutamate did not change quartz-induced haemolysis of rat erythrocytes in vitro or in vivo; chicken erythrocytes showed some reduction. In rats injected intratracheally with 50 mg of dust from quartzite rock containing 92% quartz, glutamate-treated animals had lower lung weights and hydroxyproline and less advanced silicotic nodules; in a six-month chrysotile asbestos experiment treated rats' values were lower, though only the body-weight-corrected hydroxyproline difference was marked significant.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: experimental animal and cell-culture study (in vitro macrophage and erythrocyte tests plus intratracheal dust experiments in rats), summarising several of the authors' experiments
• Who was studied: Rat peritoneal macrophage cultures and rat (and chicken) erythrocytes; 10 glutamate-drinking and 10 control rats in the macrophage-resistance experiment; about 8-10 and 7-13 rats per group in the intratracheal dust experiments; Institute of Industrial Hygiene and Occupational Diseases, Sverdlovsk, USSR
• Exposure: Quartz dust DQ12 in vitro (1.0, 2.0 and 5.0 mg per sample); intratracheal injection of 50 mg of dust from ground quartzite rock containing 92% quartz; chrysotile asbestos dust; treatment with glutamic acid in vitro (25, 50 or 500 micrograms per millilitre) or sodium glutamate 15 mg/ml in drinking water (roughly 100 mg per 200-g rat)
• Main results:
  • In macrophage cultures exposed to 2 mg quartz, TTC-reductase activity was 56.7 in controls versus 75.1 after preincubation with glutamic acid 25 micrograms per millilitre; 59.6 versus 83.5 at 50 micrograms per millilitre; and 45.7 versus 74.7 at 500 micrograms per millilitre
  • These activity values were percentages of the activity of control cultures not acted on by glutamate or quartz
  • The quartz dose theoretically corresponding to 50% inhibition, determined graphically, was 2.8 mg for control cultures and 7.2 mg for cultures preincubated with glutamic acid, described by the authors as an average 2.6-fold increase in resistance
  • Macrophages from rats drinking sodium glutamate solution showed less quartz-induced inhibition than those from water-drinking rats at one, two and four months (for example 77.9 versus 58.7 at one month), expressed relative to macrophages of the same rat not exposed to quartz
  • Glutamate produced no influence on rat erythrocytes, whose quartz-induced haemolysis was unaltered by glutamic acid in vitro or glutamate in vivo
  • In chicken erythrocytes, haemolysis at all quartz doses tested was to some degree reduced by preincubation with glutamic acid (50 micrograms per millilitre), the difference at the 2 mg dose being marked p less than 0.05
  • In macrophages not exposed to quartz, the ATP/ADP ratio after two months rose in both groups but was higher in the glutamate group (4.63) than in controls (3.47)
  • No change in total adenosine nucleotide content or the ADP/ATP ratio was seen in rat erythrocytes from rats given glutamate
  • In quartz-injected rats, untreated animals reached third to fourth stage fibrosis by six months while glutamate-treated animals generally developed only second-stage nodules; at six months lung hydroxyproline was 13137 for dust only versus 9284 for dust plus glutamate
  • In the six-month chrysotile-asbestos experiment, dust-exposed rats had dry lung weight 425.0 and lung hydroxyproline 7678 versus 391.6 and 6285 in dust plus glutamate rats; these absolute values were not marked as differing significantly from dust alone, whereas the body-weight-corrected hydroxyproline (3910.0 versus 3062.0) was so marked
  • When glutamate treatment began only one month after quartz injection, treated rats had separated nodules of stage 1 or 2 at six months versus third to fourth stage conglomerating nodules in untreated rats, with a statistically significant difference in hydroxyproline content
• The authors' conclusion: The authors concluded that glutamate increased macrophage resistance to quartz cytotoxicity, most probably through its influence on membrane stability and adenosine nucleotide metabolism, and that this underlies the delay in silicotic fibrosis; they suggested silicosis could be added to conditions whose treatment and prophylaxis may be supplemented by glutamate, while stating further analysis was needed
• Limitations the authors state:
  • The authors stated the precise mechanism of glutamate's protective action on macrophages is not known
  • The authors stated that the adenosine nucleotide shifts were difficult to reproduce fully because of opposing influences
  • The authors noted that results of two further experimental series were not included in this paper and were published elsewhere
  • The authors noted the peritoneal macrophages used rely on oxidative phosphorylation less than alveolar macrophages

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Fibrosis.

Related studies

• A spin label study of the effects of asbestos, quartz, and titanium dioxide dusts on the bovine erythrocyte membrane — W. Leyko, E. Gendek (1985)
• Kinetics of the bronchoalveolar leucocyte response in rats during exposure to equal airborne mass concentrations of quartz, chrysotile asbestos, or titanium dioxide — K. Donaldson, R.E. Bolton, et al. (1988)
• Ultrastructure of the lung in the rat following exposure to crocidolite asbestos and quartz — K. Miller, I. Webster, et al. (1978)
• The effect of different mineral dusts on the mechanism of phagocytosis: a scanning electron microscope study — K. Miller, R.I. Handfield, et al. (1978)
• Cytotoxicity of respirable dusts from industrial minerals: comparison of two naturally occurring and two man-made silicates — D. Nadeau, L. Fouquette-Couture, et al. (1987)
• Fibrogenic effect of wollastonite compared with asbestos dust and dusts containing quartz — M. Cambelová, A. Juck (1994)

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