Acta Scientific Microbiology (ISSN: 2581-3226)

Research ArticleVolume 4 Issue 3

The Effects of Acute Intoxications with 1,2-Dichloroethane, Tetrachloromethane and Trichloroethylene on Innate Immunity Parameters

Pavel F Zabrodskii1*, Vladimir G Lim2 and Vladimir K Parfenyuk3

1Saratov Medical University "REAVIZ", Saratov, Russia
2I.M. Sechenov First Moscow State Medical University, Moscow, Russia
3Saratov State Medical University named after V. I. Razumovsky, Saratov, Russia

*Corresponding Author: Pavel F Zabrodskii, Saratov Medical University "REAVIZ", Saratov, Russia.

Received: December 21, 2020; Published: February , 2021

Citation: Pavel F Zabrodskii., et al. “The Effects of Acute Intoxications with 1,2-Dichloroethane, Tetrachloromethane and Trichloroethylene on Innate Immunity Parameters”. Acta Scientific Microbiology 4.3 (2021): 02-05.

Abstract

  Chlorinated hydrocarbons (ChH) - 1,2-dichloroethane (DchE), tetrachloromethane (TChM), and trichloroethylene (TChE) are widely used in industry as solvents for oils, fats, rubber and resins etc. Despite the low frequency of acute intoxication with these compounds (up to 5%), they are characterized by very high lethality (32-96%). Experiments on random-bred albino rats showed that chlorinated hydrocarbons acute intoxications (DchE, TChM, TChE) a single dose of 0.8 LD50 causes a reduction the integral state of the innate immunity (increased mortality of rats from experimental infection by 27.8-41.9% caused by P. vulgaris, decreased LD50 P. vulgaris by 1.58-1.68 times, mean effective lifetime of animals (Et50) by 1.70-2.08 times (p < 0.05). ChH acute intoxications decreased the parameters of innate immunity (bactericidal activity of blood serum by 1.43-1.60 times, serum concentrations of lysozyme by 1.70-2.27 times and platelet cationic protein by 1.38-1.62 times, activity of natural killer cells (NK) by 1.73-2.20 times, increases the contents of P. vulgaris in peripheral blood by 1.96-2.37 times and spleen by 1.70-1.98 times in the modeling of an experimental infection (p < 0.05). No significant differences were found between parameters of the integral state of the innate immunity and the parameters of innate immunity after various chlorinated hydrocarbons acute intoxications (p > 0.05).

Keywords: Chlorinated Hydrocarbons; Immunotoxicity; Innate Immunity; NK; P. vulgaris

Introduction

  Chlorinated hydrocarbons (СhH) - 1,2-dichloroethane (DChE, ethylene dichloride), tetrachloromethane (TChM, carbon tetrachloride, perchlormethane, methane tetrachloride, Freon-10, Halon-104) and trichloroethylene (TChE, 1,1,2-Trichloroethylene, 1-chloro-2,2-dichloroethylene, 1-chloro-2,2-dichloroethylene, ethylene trichloride, trilene) are widely used in industry as solvents for oils, fats, rubber and resins, for dry-cleaning clothes etc. [1]. These chlorinated hydrocarbons can affect virtually all body organs and systems [1,2] and, if intoxicated, can enter the body through the respiratory tract (less commonly through the skin and digestive tract), they have allergic [3], mutagenic and carcinogenic properties [1,4], affect kidneys [1,3,5] and liver [1,3,6], cause autoimmune diseases [1], and have immunotoxic [1] and psychotropic effects [1,3]. Common in toxicokinetics of ChH is their ability to metabolize with the formation of more toxic compounds ("lethal synthesis") [1,7]. Acute group poisonings of СhH are possible in case of violations of safety precautions when handling them, as well as in emergency situations at chemical plants. Consumption of СhH as an alcohol surrogate or for suicidal purposes cannot be excluded [1,7]. In recent years, the frequency of acute intoxication with ChH and the mortality rate from intoxications have not decreased. Despite the low frequency of acute intoxication with these compounds (up to 5%), they are characterized by very high lethality (32-96%) [1,7].

  One of the causes of lethality after CHG acute intoxications may be infectious complications and diseases associated with reduced innate immunity as a result of the immunotoxic effects of both CHGs and their highly toxic metabolites. A study of the effect of ChH on innate immunity parameters is necessary to substantiate the correction of post-intoxication disorders in order to prevent various infectious complications [1].

Aim of the Study

  The aim of the study was a comparative assessment of changes basic parameters of innate immunity after acute intoxication with chlorinated hydrocarbons (1,2-dichloroethane, tetrachloromethane and trichloroethylene).

Materials and Methods

  The experiments were performed on random-bred albino rats of both sexes weighing 180-240 g. ChH (Sigma-Aldrich) was administered intragastrically (per os) a single dose of 0.8 LD50 in an olive oil solution. LD50 of 1,2-dichloroethane (DchE), tetrachloromethane (TChM) and trichloroethylene (TChE) for rats after intragastrically administration was 0,75+0,10; 6,1+0,3 and 4,7 +0,4 mg/kg, respectively). Control animals received per os equal volume of olive oil. Four groups of rats (control, rats injected with DchE, TChM, TChE) were injected with P. vulgaris 1 day after administration of olive oil (control) and ChH. The integral state of the innate immunity was determined by the indices of the experimental infection course caused by intrapulmonary injection of Р. vulgaris daily culture suspension in a single doses of 1.5×109, 2.0×109 and 3.0×109 CFUs in 1.5-3.0 ml of saline (three groups of rats, with 7 animals in each group) [8,9].

  The integral state of the innate immunity was evaluated by mortality of rats (Р. vulgaris intrapulmonary) during 36 h from experimental infection, as well as by mean lethal doses (LD50) of P. vulgaris and mean effective lifetime of animals (Et50) in experimental and control groups calculated by probit analysis [8].

  The bactericidal activity of blood serum (BABS) of rats, serum concentrations of lysozyme and platelet cationic protein (PCP), activity of NK, and contents of P. vulgaris in peripheral blood (CFUs in 0.05 ml) and spleen (CFUs x 102) of surviving mice was determined after intrapulmonary injection of the Р. vulgaris daily culture suspension in a single doses of 1.5×109 CFUs in 1.5 ml of saline by conventional methods [1,10]. These parameters of innate immunity were evaluated 48 h after ChH administration.

  The data obtained were processed statistically using the Student's t-test. Differences between the parameters were considered reliable at p < 0.05.

Results

  Under the influence of DchE, TChM, TChE acute intoxications at dose of 0.8 LD50 the mortality of rats from experimental infection increased in comparison with the control, respectively, by 41,9% (p < 0.05), 32,4% (p < 0.05) and 27,6% (p < 0.05); decreased LD50 P. vulgaris by 1.58 (p < 0.05), 1.62 (p < 0.05), 1.68 times (p < 0.05) and Et50 of rats - by 1.85 (p < 0.05), 2,09 (p < 0.05), and 1.70 times (p < 0.05), respectively, indicating the integral state of the innate immunity suppression (table). No significant differences were found between parameters of the integral state of the innate immunity after DchE, TChM, TChE acute intoxications (p > 0.05).

Parameters Control DhE TChM TChE
Mortality, % 20, ± 0 5,2 (60) 61,9 ± 10,6* (21) 52,4 ± 10,9* (21) 47,6 ± 9,0* (21)
LD50 Р. vulgaris, 109 CFUs 2,54 ± 0,08 (60) 1,61+0,16* (21) 1,57+0,18* (21) 1,51+0,19*(21)
Et50, h 19,2 ± 1,3 (60) 10,4 ± 2,4* (21) 9,2 ± 2,3* (21) 11,3 ± 2,4*(21)
BABS, % 80,1 ± 8,8 (20) 55,2 ± 6,1* (8) 50,0 ± 6,2*(9) 56,1 ± 7,0*(10)
Lysozyme, mg/l 7,5 ± 0,4 (20) 3,1 ± 0,6* (8) 4,4 ± 0,7* (9) 3,3 ± 0,5*(10)
PCP, % 62,0 ± 2,9 (20) 43,0 ± 4,6* (8) 38,3 ± 4,4* (8) 45,0 ± 4,7* (9)
NK activity, % 26,4 ± 3,1 (20) 13,1 ± 4,0* (8) 12,0 ± 3,8* (9) 15,3 ± 4,5* (10)

Content of Р. vulgaris of peripheral blood (CFUs in 0.05 ml) 37,2 ± 6,4 (7) 85,5 ± 8,2*(7) 73,0 ± 6,5*(7) 88,1 ± 9,7* (7)
Number of Р. vulgaris in spleen, CFUs x 102 90,0 ± 15,2 (7) 169,0 ± 19,7* (7) 178,0 ± 18,8* (7) 153,0 ± 17,9* (7)

Table : Effect of chlorinated hydrocarbons acute intoxication (0,8 LD50) on integral state of the innate immunity and parameters of innate immunity of albino rats (M ± m)
* -p <0,05 as compared to control; in parentheses - the number of animals.

   After DchE, TChM, TChE acute intoxications decreased BABS in comparison with the control, respectively, by 1,45 (p < 0.05), 1.60 (p < 0.05) and 1.43 (p < 0.05) times, serum concentrations of lysozyme with the control by 2,42 (p < 0.05), 1.70 (p < 0.05) and 2.27 (p < 0.05) times, PCP - by 1,44 (p < 0.05), 1.62 (p < 0.05) and 1.38 (p < 0.05) times, activity of NK - by 2,02 (p < 0.05), 2.20 (p < 0.05) and 1.73 (p < 0.05) times, while the content of P. vulgaris in peripheral blood (CFUs in 0.05 ml) increased by 2.30 (p < 0.05), 1.96 (p < 0.05) and 2.37 (p < 0.05) and the number of P. vulgaris in spleen (CFUs x 102) increased by 1.88, 1.98 (p < 0.05), 1.70 (p < 0.05) times (p < 0.05), respectively (table). There were no statistically significant differences (p>0.05) between the investigated parameters of innate immunity after acute intoxications with different ChH.

Discussion

   The suppression of the integral state of the innate immunity (mortality of rats, LD50 of P. vulgaris, Et50) after acute ChH intoxication is caused by a decrease in the bactericidal activity of blood serum of rats, serum concentrations of lysozyme and platelet cationic protein, activity of NK) [1].

  The mechanism of suppression of innate immunity parameters is due to the damage of almost all organs and systems of the body, in particular, the immune system organs and blood cells as a result of interaction with sulfhydryl and amino groups enzymes and highly toxic products of ChH biotransformation, leading to disruption of numerous biochemical processes in the body's cells, including inhibition of tissue respiration and oxidative phosphorylation [1,7]. Many products of ChH metabolism are known to be more toxic than DChE (2-chloroethanol, chloroacetic aldehyde, monochloroacetic acid) [1,7,11,12,13]. TChM (chlorine, phosgene, carbon monoxide, and free radicals - carbon dichloride; ССl+3; O-O-CCl; HO-OCCCl3; HO-CCl3), TChE (dichloroacetyl chloride, dichloroacetic acid, trichloroacetaldehyde, trichloroacetic acid, trichloroethanol, N-(hydroxyacetyl) ethanolamine, trichloroethanediol) [1,4].

Conclusions

   Dry eye disease should be considered as a disease of the entire ocular surface system, and all the components of the system need to be taken into account separately, which is not complicated or time-consuming. Dry eye disease is much easier to manage if the examination is made in a systematic and logical way. In the everyday clinical practice fluorescein and lissamine green are very important tool, and with one drop (or better with a calibrated quantity of stain as described by Hamrah., et al. [24]), lot of diagnostic information can be harvested without using any specific technologies. Another easy test that should be included in routine diagnostic processes is corneal sensitivity testing. In most instances this can be performed easily and time-efficiently with a cotton tip applicator.

  • Chlorinated hydrocarbons acute intoxications (1,2-dichloroethane, tetrachloromethane, trichloroethylene) a single dose of 0.8 LD50 causes a reduction the integral state of the innate immunity (increased mortality of rats from experimental infection, caused by vulgaris by 27.8-41.9%; decreased LD50 P. vulgaris by 1.58-1.68 times, mean effective lifetime of animals (Et50) by 1.70- 2.08 times. No significant differences were found between parameters of the integral state of the innate immunity after various chlorinated hydrocarbons acute intoxications.
  • Acute intoxications of 1,2-dichloroethane, tetrachloromethane, trichloroethylene reduced the parameters of innate immunity (bactericidal activity of blood serum by 1.43-1.60 times, serum concentrations of lysozyme by 1.70-2.27 times and platelet cationic protein by 1.38-1.62 times, activity of NK by 1.73-2.20 times, increases the contents of vulgaris in peripheral blood by 1.96-2.37 times and spleen by 1.70-1.98 times in the modeling of experimental infection. There were no statistically significant differences between the investigated parameters of innate immunity after acute intoxications with different chlorinated hydrocarbons.

Bibliography

  1. Zabrodskii PF and Mandych VG. “Immunotoxicology of xenobiotics”. Saratov Military Institute of Biological and Chemical Safety (2007): 420.
  2. Hotchkiss JA., et al. “Acute toxicologic and neurotoxic effects of inhaled 1,2-dichloroethane in adult Fischer 344 rats”. Food and Chemical Toxicology 2 (2010): 470-481.
  3. Manibusan MK., et al. “Postulated carbon tetrachloride mode of action: a review”. Journal of Environmental Science and Health, Part C 3 (2007): 185-209.
  4. Lash LH., et al. “Trichloroethylene biotransformation and its role in mutagenicity, carcinogenicity and target organ toxicity”. Mutation Research - Reviews in Mutation Research 762 (2014): 22-36.
  5. Kim S., et al. “In vivo protective effect of phosphatidylcholine on carbon tetrachloride induced nephrotoxicity”. Experimental and Toxicologic Pathology 10 (2016): 553-558.
  6. Wang XZ., et al. “Effects of transmitters and interleukin-10 on rat hepatic fibrosis induced by CCl4”. World Journal of Gastroenterology9 (2003): 539-543.
  7. EA Luzhnikov and LG Kostomarova. “Acute intoxications: A guide for doctors”. 2nd ed. revised and supplemented. Moscow, "Medicine" (2000): 343.
  8. Zabrodskii PF. “Effect of armin on nonspecific resistance factors of the body and on the primary humoral immune response”. Farmakologiia I Toksikologiia1 (1987): 57-60.
  9. Song DJ., et al. “Effect of lentiviral vector encoding on triggering receptor expressed on myeloid cells 1 on expression of inflammatory cytokine in septic mice infected by Bacteroides fragilis”. Zhonghua Shao Shang Za Zhi1 (2009): 36-41.
  10. PF Zabrodskii. “Immunotoxicology of organophosphorus compounds”. Saratov (2016): 289.
  11. Zabrodskii PF., et al. “Anticholinesterase mechanism as a factor of immunotoxicity of various chemical compounds”. Bulletin of Experimental Biology and Medicine 2 (2003): 176-178.
  12. Zabrodskiĭ PF., et al. “Stimulation of immunotoxicity of chemicals metabolizing in vivo into highly toxic compounds by the monooxygenase system inductors”. Bulletin of Experimental Biology and Medicine 4 (2004): 369-371.
  13. Zabrodskiĭ PF., et al. “Inhibition of cytochrome P-450 with 2-diethylamino-ethyl-2,2-diphenylpropylacetate (SKF-525A) reduces immunotoxicity of chlorinated carbohydrates”. Bulletin of Experimental Biology and Medicine 3 (2006): 324-326.

Copyright: © 2021 Pavel F Zabrodskii., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.



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