Kostic, Tomislav, Popović, Dejan, Perisic, Zoran, Stanojevic, Dragana, Dakic, Sonja, Saric, Sandra, Radojkovic, Danijela Djordjevic, Apostolovic, Svetlana, Bozinovic, Nenad, Zdravkovic, Snezana Ciric, Milutinovic, Stefan, Maricic, Bojan, Živković, Nikola, Golubovic, Mladjan, Djordjevic, Miodrag, Damjanović, Radomir, Bell, Abraham, and Đinđić, Boris
In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl 4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl 4 , at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H 2 O 2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl 4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1β, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl 4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl 4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl 4. The hepatoprotective mechanisms in CCl 4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis. [Display omitted] • Aminoguanidine ameliorates the acute hepatotoxicdamage caused by CCl4. • Aminoguanidine prevents lipid peroxidation anddecreases oxidative stress. • Aminoguanidine prevents the diversion of the arginine metabolism towards citrulline. • Aminoguanidine decreases the pro-inflammatory markers (NGAL, TNF-α, IL-1β, IL-6, NO). • Aminoguanidine induces cell damage into apoptosis in CCl4 acute liver damage. [ABSTRACT FROM AUTHOR]