Damira F. Avgustinovich

The widespread use of nanotechnology means that humans contact with nanoparticles every day: orally, through the skin and lungs, or via medical treatment. Silicon dioxide (SiO₂) is one of the most commonly used nanoparticles. The intake of SiO₂ nanoparticles against the background of parasitic infections is a special case. We model the combination of two factors: consumption of water containing amorphous SiO₂ nanoparticles by mice along with infection by Opisthorchis felineus (OF). The states of the liver, major opisthorchiasis target, and of immunocompetent organs, the spleen and thymus, were assessed. Changes in the blood, which connects all organs and systems in the body, were also considered. Prolonged consumption of the nanoparticles caused no significant changes in the assessed parameters in uninfected animals. Pronounced hepatomegaly and splenomegaly were caused by OF infection. Inflammatory infiltration and extensive fibrosis of the bile ducts persisted during the concurrent consumption of SiO₂ nanoparticles. The enlarged spleen of OF + SiO₂ mice showed most pronounced changes. In contrast, the consumption of silicon water normalized the relative levels of certain blood parameters that had changed during the OF infection. We infer that the action of amorphous SiO₂ nanoparticles depends on the organ and the body’s overall physiological state.

Our purpose was to model a combination of a prolonged consumption of ethanol with Opisthorchis felineus infection in mice. Four groups of C57BL/6 mice were compiled: OF, mice infected with O. felineus for 6 months; Eth, mice consuming 20 % ethanol; Eth+OF, mice subjected to both adverse factors; and CON, control mice not exposed to these factors. In the experimental mice, especially in Eth+OF, each treatment caused well-pronounced periductal and cholangio fibrosis, proliferation of bile ducts, and enlargement of areas of inflammatory infiltration in the liver parenchyma. Simultaneously with liver disintegration, the infectious factor caused – in the frontal cerebral cortex – the growth of pericellular edema (OF mice), which was attenuated by the administration of ethanol (Eth+OF mice). Changes in the levels of some proteins (Iba1, IL-1β, IL-6, and TNF) and in mRNA expression of genes Aif1, Il1b, Il6, and Tnf were found in the hippocampus and especially in the frontal cortex, implying region-specific neuroinflammation. Behavioral testing of mice showed that ethanol consumption influenced the behavior of Eth and Eth+OF mice in the forced swimming test and their startle reflex. In the open field test, more pronounced changes were observed in OF mice. In mice of all three experimental groups, especially in OF mice, a disturbance in the sense of smell was detected (fresh peppermint leaves). The results may reflect an abnormality of regulatory mechanisms of the central nervous system as a consequence of systemic inflammation under the combined action of prolonged alcohol consumption and helminth infection.

Opisthorchiosis is a parasitic liver disease found in mammals that is widespread throughout the world and causes systemic inflammation. Praziquantel remains the drug of choice for the treatment of opisthorchiosis, despite its many adverse effects. An anthelmintic effect is attributed to the main curcuminoid of Curcuma longa L. roots—curcumin (Cur)—along with many other therapeutic properties. To overcome the poor solubility of curcumin in water, a micellar complex of curcumin with the disodium salt of glycyrrhizic acid (Cur:Na₂GA, molar ratio 1:1) was prepared via solid-phase mechanical processing. In vitro experiments revealed a noticeable immobilizing effect of curcumin and of Cur:Na₂GA on mature and juvenile Opisthorchis felineus individuals. In vivo experiments showed that curcumin (50 mg/kg) had an anthelmintic effect after 30 days of administration to O. felineus-infected hamsters, but the effect was weaker than that of a single administration of praziquantel (400 mg/kg). Cur:Na₂GA (50 mg/kg, 30 days), which contains less free curcumin, did not exert this action. The complex, just as free curcumin or better, activated the expression of bile acid synthesis genes (Cyp7A1, Fxr, and Rxra), which was suppressed by O. felineus infection and by praziquantel. Curcumin reduced the rate of inflammatory infiltration, whereas Cur:Na₂GA reduced periductal fibrosis. Immunohistochemically, a decrease in liver inflammation markers was found, which is determined by calculating the numbers of tumor-necrosis-factor-positive cells during the curcumin treatment and of kynurenine-3-monooxygenase-positive cells during the Cur:Na₂GA treatment. A biochemical blood test revealed a normalizing effect of Cur:Na₂GA (comparable to that of curcumin) on lipid metabolism. We believe that the further development and investigation of therapeutics based on curcuminoids in relation Opisthorchis felineus and other trematode infections will be useful for clinical practice and veterinary medicine.

Background Praziquantel (PZQ) is the most commonly used anthelmintic drug for treating trematodiases. It was shown here that PZQ in complex with disodium glycyrrhizinate (PZQ-Na₂GA, in the 1:10 ratio) has higher bioavailability than PZQ alone. Our aim was to determine the effects of three-time administration of PZQ-Na₂GA in an experimental opisthorchiasis felinea model. Methods The PZQ-Na₂GA complex (1:10) at a 400 mg/kg dose (meaning 36.4 mg/kg PZQ) was administered to Opisthorchis felineus-infected hamsters three times under a “9:00 am–6:00 pm–9:00 am” regimen (PZQ-Na₂GA × 3). Effects of treatment were assessed as a reduction of helminth load in the hamsters and as changes in physiological, hematological, and blood biochemical parameters. The helminths extracted from the liver of the hamsters that received PZQ-Na₂GA thrice were assayed for sensitivity to PZQ in vitro. Results PZQ-Na₂GA × 3 reduced the number of O. felineus helminths in the liver by 87%, which is 30% better than a previously reported effect of one-time administration of the complex. Meanwhile, relative weights of the liver and thymus diminished, and some hematological parameters improved. The helminths extracted from the hamsters 1 month after the PZQ-Na₂GA × 3 treatment showed elevated sensitivity to PZQ, as determined in vitro. Conclusion Compared with previously published data on the effectiveness of various drugs in experimental opisthorchiasis felinea, PZQ-Na₂GA × 3 exerts the most potent anthelmintic effect. In addition, PZQ-Na₂GA × 3 improves physiological status of O. felineus-infected hamsters and sensitizes the surviving parasites to subsequent PZQ treatment.

Background Nowadays, it is still important to develop effective anti-opisthorchiasis agents. In this work, we tested a complex of praziquantel (PZQ) with a plant origin compound—disodium...