THE PROTECTIVE EFFECT OF GERMANIUM CITRATE ON FUNCTIONAL STATE OF IMMUNE CELLS AND NEUTROPHIL ACTIVITY UNDER THE CONDITION OF LIPOLYSACCHARIDE INDUCED INFLAMMATION
N.G. Grushka, S.I. Pavlovych, O.A. Kondratska, N.O. Pilkevcih, R.I. Yanchii
О.О. Bogomoletz Institute of Physiology, NAS of Ukraine, Kyiv, Ukraine
In the present work we investigated the effect of germanium
(Ge) citrate, which has antioxidant properties, on functional
and metabolic activity of neutrophils, degree of DNA damage
and pathways of thymus and lymph node cell death under the
conditions of systemic endotoxemia in mice. It was found that
the administration of E. coli lipopolysaccharide (LPS) (3 mg/
kg) induced a systemic inflammatory process with significant
damage to cells and organs. Introduction of LPS caused the
activation of the nonspecific resistance cells (according to the
nitroblue tetrazolium test and the lysosomal-cationic test),
which is an important mechanism of the cytotoxic effect
of LPS. There was severe damage to DNA of thymus and
lymph node cells, reducing their viability and an increase
in the number of cells with signs of apoptosis or necrosis.
The use of Ge citrate under the conditions of LPS treatment
reduced generation of reactive oxygen species in neutrophils,
as evidenced by a decrease in the percentage of formazanpositive
cells and the cytochemical index. The content of
cationic proteins and inflammatory mediators, according to
the average cytochemical coefficient, was also decreased. In
addition, administration of Ge citrate resulted in a reduce of
the degree of DNA damage in thymus and lymph node cells,
as well as in weakening necrotic and apoptotic cell death.
Thus, the use of Ge citrate had a protective effect on thymus
and lymph node cells reducing their DNA damage and death,
which can be mediated by the normalization of neutrophil
functions revealed in our experiments. The data obtained
indicate the promise of the use of Ge citrate in the complex
prevention and treatment of endotoxin induced diseases in
humans and animals.
germanium citratе; lipopolysaccharide; immune cells; DNA damage; apoptosis; necrosis.
- Shen S, Han F, Yuan A, Wu L, Cao J, Qian J, Qi X, Yan Y, Ge Y. Engineered nanoparticles disguised as macrophages for trapping lipopolysaccharide and preventing endotoxemia. Biomaterials. 2019;189:60-8.
- Ajuwon OR, Oguntibeju OO, Marnewick JL. Amelioration of lipopolysaccharide-induced liver injury by aqueous rooibos (Aspalathus linearis) extract via inhibition of pro-inflammatory cytokines and oxidative stress. BMC Complementary and Alternative Medicine. 2014;14:392.
- Buttenschoen K, Radermacher P, Bracht H. Endotoxin elimination in sepsis: physiology and therapeutic application. Langenbecks Arch Surg. 2010;395(6):597-605.
- Fedoruk RS, Tesarivska UI, Khrabko MI, Tsap MM, Dolaychuk OP, Kropyvka SI. Haematological and biochemical parameters of the F2 rats' organism in a period of prolonged watering of nano-Ge citrate. Animal Biol. 2017;19(3):115-21. [Ukrainian].
- Li L, Ruan T, Lyu Y, Wu B. Advances in effect of germanium or germanium compounds on animals A review. Biosci and Med. 2017;5(7):56-73.
- Nakamura T, Takeda T, Tokuji Y. The oral intake of organic germanium, Ge-132, elevates α-Tocopherol levels in the plasma and modulates hepatic gene expression profiles to promote immune activation in mice. Int J Vitam Nutr Res. 2014;84(3-4):183-95.
- Fedoruk RS, Khrabko MI, Tsap MM, Martsynko OE. Growth, development and reproductive function of female rats and their offspring viability at the conditions of the watering of different doses of citrate germanium. Animal Biol. 2016;18(3):97-106. [Ukrainian].
- Dolaychuk OP, Fedoruk RS, Kropyvka SJ. Physiological reactivity and antioxidant defense system of the animal organism induced by germanium, chromium, and selenium "Nanoaquacitrates". Agricult Sci Pract. 2015;2(2):50-5.
- Kosinov MV, Kaplunenko VG. Pat. of Ukraine No. 38391. 2009. Method for metal carboxylates obtaining "Nanotechnology of obtaining metal carboxylates". N a 200810939; appl. 08.09.2008; publ. 12.01.2009; Bull. N 1:5 p.
- Lymphocytes: Methods: Edited by J. Claus. Publishing house "Mir", Moscow, 1990. [Russian].
- Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26(3):249-61.
- Shepel E, Grushka N, Makogon N, Sribna V, Pavlovych S, Yanchii R. Changes in DNA integrity and gene expression in ovarian follicular cells of lipopolysaccharide-treated female mice. Pharmacol Rep. 2018;70(6):1146-9.
- Grushka N.G. The effect of poly(ADP-ribose) polymerase inhibitor 4-hydroxyquinazoline on death of immune cells under immune complex-mediated injury in mice. Fiziol Zh. 2017;63(1):43-50. [Ukrainian].
- Metcalf JA, Gallin JI. Nauseef WM. Root RK. Laboratory manual of neutrophil function. NY; Raven Press; 1986.
- Nagalievska M, Sabadashka M, Hachkova H, Sybirna N. Galega officinalis extract regulate the diabetes mellitus related violations of proliferation, functions and apoptosis of leukocytes. BMC Complement Altern Med. 2018;18(1):4.
- Kuzmich NN, Sivak KV, Chubarev VN, Porozov YB, Savateeva-Lyubimova TN, Peri F. TLR4 signaling pathway modulators as potential therapeutics in inflammation and sepsis. Vaccines (Basel). 2017;5(4). pii: E34.