Toxicological assessment of nanostructured silica. II. Enzymatic, biochemical indices, state of antioxidative defence
Nanostructured silica (SiO2) ≪Aerosil≫ with the size of the primary nanoparticles (NPs) of 5–30 nm, in the form of ultrasound treated water suspension was administered to rats of 80Ѓ}4 g initial body weight for the first 30 days by intragastric gavage and then for 62 days with diets consumed in doses of 0,1; 1,0; 10 and 100 mg/kg body weight per day. The control group received vehicle of nanomaterial (NM) – deionized water. There were measured in liver of animals the content of total cytochromes P450 and b5 in the microsomal fraction of liver, activity (Vmax) of microsomal monooxygenases with the mixed function of isoforms CYP1A1, 1A2 and 2B1 on their specific substrates, the activity of conjugating liver enzymes glutathione-S-transferase and UDP-glucuronosyltransferase in microsomal fraction and cytosol, the total and non sedimentable activity of lysosomal hydrolases (β-glucuronidase, β-galactozydase, arylsulphatase А, В). The content of PUFA’s diene conjugates and TBA-reactive substances in the blood plasma and the activity of antioxidative enzymes (glutathionperoxidase, superoxidedismutase, glutathionreductase, katalase) in erytrocytes were estimated. A set of standard biochemical parameters of blood serum was also examined (total protein, albumin, glucose, creatinine, urea, uric acid, activities of hepatic transaminases). The studies revealed changes of a number of molecular markers that could be interpreted as unfavorable. These include isoforms of CYP2B1 activity decrease at a dose HM 1–10 mg/kg of body weight, decrease in the serum content of total protein, albumin and glucose levels in a dose range of 0,1–10 mg/kg. These changes were absent at the maximum dose of NM, which did not allow to clearly establish the dose-response. The remaining studied figures resided in the normal range or experienced changes that could not be interpreted as toxic.
Keywords:silica, nanoparticles, rats, subacute toxicity, microsomes, CYP450, lysosomes, non sedementable activity, lipid peroxidation