One of the key proinflammatory cytokines in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) is the transforming growth factor beta (TGFβ), since it promotes the accumulation of lipids by dysregulation of lipid metabolism and amplification of apoptosis of lipid-accumulation hepatocytes. TGF-β1 is encoded by the Tgfb1 gene and affects different types of cells and is involved in the remodeling of the extracellular matrix. In the process of development of nonalcoholic steatohepatitis, resident immune cells of the liver are activated, and additional immune cells penetrate into the tissue. These cells produce and release cytokines, as well as small molecules of inflammatory mediators, including prostaglandin E2 (PGE2). Involvement of PGE2 and overexpression of mRNA the Ptgs2 gene encoding PGE2 in inflammatory processes in the liver is beyond doubt.

To evaluate expression of Tgfb1, Ptgs2 genes in rats hepatocytes upon development monosodium glutamate-induced steatohepatosis and after use cerium dioxide nanoparticles.

The study was done on 30 newborn Wistar male rats, divided into 3 groups, 10 animals in each: intact rats, monosodium glutamate (MSG-) and MSG + cerium dioxide nanoparticles.

Rats of intact group were administered with saline (8 μl/g, subcutaneously (s.c.)). Newborn rats of MSG-group and MSG + cerium dioxide nanoparticles were injected with a solution of MSG (4 mg/g) s.c. at 2nd – 10th postnatal days. In a month the MSG + cerium dioxide nanoparticles group periodically (2 week in a month to the end of 4th month) was treated with cerium dioxide nanoparticles (4 mg/kg).

RNA we obtained by Chomczynski (1987). Synthesis of kDNA and real-time quantitative polymerase chain reaction (Real-time PCR, kPLR) were performed using commercial kit Thermo Scientific Verso SYBR Green 1-Step qRT-PCR ROX Mix (Lithuania).

In rats with glutamate-induced steatohepatosis expression of Tgfb1 gene in hepatocytes was increased by 1,7 times (p < 0,001) in comparison with control. In rats with glutamate-induced steatohepatosis upon periodical treatment by cerium dioxide nanoparticles, expression of Tgfb1 gene in hepatocytes was almost 1,3 times (р < 0,01) less than in animals with glutamate-induced steatohepatosis against the background of periodical treatment of saline. At the same time, it remained elevated by 1,35 times (p < 0,01) relative to control. The level of expression of Ptgs2 gene in hepatocytes in rats with steatohepatosis was higher by 8,2 times (p < 0,001) compared to control rats. In rats with steatohepatosis which were treated by cerium dioxide nanoparticles this means was lower by 4,8 time (р < 0,001) than in animals with glutamate-induced steatohepatosis without treatment. However, expression of Ptgs2 gene did not return to the level of control and was increased by 1,7 time in comparison with intact control rats.

Glutamate-induced steatohepatosis is accompanied by the changes in expression of the Tgfb1, Ptgs2 genes in rat hepatocytes, whereas upon administration of cerium dioxide nanoparticles the pattern of studied gene expression was significantly smaller, although it did not return to the level of control.

Recieved: 09.02.2019

Keywords: steatohepatosis, expression of Tgfb1, Ptgs2 genes, cerium dioxide nanoparticles

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