Toxicological evaluation of colloidal nano-sized silver stabilized polyvinylpyrrolidone. III. Enzymological, biochemical markers, state of antioxidant defense system
Nanosized colloidal silver (NCS) with primary nanoparticles (NPs) size in the range of 10–80 nm in aqueous suspension was administered to rats with initial weight 80±10 g for the first 30 day intragastrically and for lasting 62 days with the diet consumed in doses of 0.1; 1.0 and 10 mg/kg of body weight b.w.) per day based on silver (Ag). The control animals received deionized water and carrier of NPs – aqueous solution of stabilizer polyvinylpyrrolidone. Activity (Vmax) was determined in liver of microsomal mixed function monooxygenase isoforms CYP 1A1, 1A2 and 2B1 against their specific substrates, the activity of liver conjugating enzymes (glutathione-S-transferase and UDP-glucuronosyltransferase) in the microsomal fraction and a cytosol, and the overall and non-sedimentable activities of lysosomal hydrolases. In blood plasma there were evaluated malonic dialdehyde, PUFA diene conjugates, in erythrocytes – the activity of antioxidant enzymes. A set of standard biochemical indicators of blood serum was also determined. The studies revealed changes in a number of molecular markers of toxic action. Among them – the increase in the activity of key enzymes I and II stages of detoxification of xenobiotics, indicating its functional overvoltage; reducing the activity of glutathione peroxidase (GP), the total arylsulfatase A and B, β-galactosidase (in the absence of changes in their non-sedimentable activity), levels of uric acid, increased alkaline phosphatase activity. These changes occurred mainly at the dose Ag of 10 mg/kg b.w., except for the GP to which the threshold dose was 1 mg/kg b.w. No significant changes in the studied markers in a dose Ag 0,1 mg/kg b.w. were identified. Possible mechanisms of the toxic action of silver NPs are discussed.
Keywords:silver, nanoparticles, rats, subacute toxicity, microsomes, cytochrome P450, lysosomes, non-sedimentable activity, lipid peroxidation, trace elements