Background. Polymeric materials and plastics during the all stages of exploitation are important sources of the low-molecular chemical components, which can cause nephrotoxicity even at the threshold levels. But the pathogenetic mechanisms, especially of their combined action on the fatty acids metabolism still are insufficiently studied.

Purpose. To find out the mechanisms of the combined action of threshold doses of cadmium and dibutyl phthalate on the fatty acid composition and ratio in the renal tissues as an important element of the pathology formation; to justify their use as informative biomarkers in diagnostics, treatment and prevention of nephropathies.

Materials and methods. The studies have been carried out at 32 white male rats (4 groups of 8 individuals each) in compliance with the European requirements of bioethics. The animals have been subcutaneously injected 0.2 ml of Freund’s complete adjuvant FCA) into 0.2 ml of 0.9 % NaCl solution, and after 3 days to the first group 0.2 ml of FCA in 0.2 ml of 0.9 % NaCl (control); the second - dibutyl phthalate (DBP) at a dose of 1/100 from the DL50 (5.0 mg / kg) + FCA, the third - CdCl2 at a dose of 1/100 from the DL50 (0.3 mg/kg b) + FCA and 4-th - combination of DBP + CdCl2 + FCA. After 10 days, a provocation has been made by administering a half of the mixtures doses. On the 33rd day the reaction of the leukocytes on specific agglomeration of (RLSA) and the number and ratio of the major leukocyte species in the peripheral blood have been determined. On the 72nd day the amount of malonic dialdehyde (MDA), the activity of glutathione peroxidase (GP, KF 1.11.1.9), glutathione reductase (GR, KF 1.6.4.2), glucose-6-phosphate dehydrogenase (G6PDH, KF 1.1.1.49), the fatty acid (FA) spectrum have been identified. Statistical processing of the results has been carried out using a complex of programs in Microsoft Excel.

Results. The DBP and combinations of DBP + CdCl2 administration on the 33rd day of exposure have caused the allergic reaction, and on the 72nd day - changes of FA composition in the kidney: the increase of the total amount of saturated (more than 1.3-1.8 times ) and the decrease of the ratio of polyunsaturated to monounsaturated FA in 1.6-4.6 times (p < 0.05). The levels of regulatory eicosatrienoic and arachidonic acids have been decreased by 50.7-60.0 and 20.8-82.9 %, respectively, which correlates with the changes of the cellular immunity of toxic-allergic genesis (growth of the RLSA and lymphocytic-macrophage type of leukocyte grams). The chemical aggression, even at the threshold level, causes the restructuring of lipid peroxidation (MDA) and the activity of glutathione antioxidant enzymes (GP + GH + G-6-FDH) under DBP + Cd exposure. At the same time, cadmium exhibits not only cumulative properties, but also acts as a modulator of allergenic activity of DBP with a synergistic effect of their combined action.

Conclusions. Components of polymeric materials with isolated and, especially, combined action, cause lipid metabolism disorders and oxidative stress, which play an important role in toxic and allergic lesions of kidney tissues. Significant changes in the composition and ratios of major groups of FAs in the kidneys are informative biomarkers of early changes when exposed to low-intensity chemical factors.

Article recieved: 31.05.2018

Keywords: polymeric materials, dibutyl phthalate, cadmium, combined action, kidneys, fatty acids, immune-allergenic disorders

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1. 1. Alekseeva OG, Dueva LA. Allergy to industrial chemical compounds. M.: Medicine; 1978. 271.
2. 2. Antonomov MY. Mathematical processing and analysis of medical and biological data. K.: NII HVM VS; 2006. 558.
3. 3. ed LA. Danilova. Handbook of laboratory methods of research . St. Petersburg: Peter; 2003. 736.
4. 4. Law of Ukraine «On Protection of Animals From Cruel Treatment» of February 21, 2006, No. 3447-IV, with changes. The revision is valid from 04.08.2017.
5. 5. Cates M. Lipidology technique. M.: The World, 1975. 322.
6. 6. Kryzhanovsky GN. Dysregulation pathology. M.: Medicine 2002. 96.
7. 7. Methodical recommendations МР 8.1.4.104-2003. Investigation of the immunotoxic activity of potentially hazardous chemicals under their hygienic regulation. K.: Official publishing house; 2003. 25.
8. 8. ed Trachtenberg IM. Preventive toxicology and medical ecology. Selected lectures for scientists, doctors and students. By the general ed. Academician of the National Academy of Sciences of Ukraine IM Trachtenberg. K.: Avicenna; 2011. 320.
9. 9. Shafran LM, Gozhenko AI. Metallonephropathies: the theory and practice. Actual Problems of Transport Medicine. 2009;1(15):19-29.
10. 10. Shafran LM, Timoshina DP, Basalaeva LV. Latest developments in field hygiene and toxicology polymer and synthetic materials of the transport assignment. Actual Problems of Transport Med- icine. 2012;4(30):16-26.
11. 11. Billsanu A, Matthys P. Models of action of Freund's adjuvants in experimtntal models of autoimmune diseases. Journal of Leukocyte Biology. 2001;70(6):849-60.
12. 12. Burbure de C, Buchet J.-P, Leroyer A, Bernard A. Renal and Neurologic Effects of Cadmium, Lead, Mercury, and Arsenic in Children: Evidence of Early Effects and Multiple Interactions at Environmental Exposure Levels. Environmental Health Perspectives. 2006;114(4):584-90. doi.org/10.1289/ehp.8202
13. 13. European convention for the protection of vertebrate animals used for experimental and other scientific purposes. Council of Europe, Strasbourg; 1986. 53.
14. 14. Jadhav SH, Sarkar SN, Ram GC, Tripathi HC. Immunosuppressive effect of subchronic exposure to a mixture of eight heavy metals, found as groundwater contaminants in different areas of India, through drinking water in male rats. Archives of Environmental Contamination and Toxicology. 2007;53(3):450-8. doi.org/10.1007/s00244-006-0177-1
15. 15. Jaimes E, Hua P, Tian R, Raij L. Human glomerular endothelium: interplay among glucose, freefatty acids, angiotensin II, and oxidative stress. 2010;298(1):125-32.
16. 16. Morsali A, Hashemi L. Main group metal coordination polymers: Structures and Nanostructures. New Jersey: Wiley & Sons; 2017. 272. doi.org/10.1002/9781119370772
17. 17. Singh S, Li S. Phthalates: toxicogenomics and inferred human diseases. Genomic. 2011;97(3):148-57. doi.org/10.1016/j.ygeno.2010.11.008