Biomedicine & Pharmacotherapy (Dec 2022)

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats

  • Tomislav Kostic,
  • Dejan Popović,
  • Zoran Perisic,
  • Dragana Stanojevic,
  • Sonja Dakic,
  • Sandra Saric,
  • Danijela Djordjevic Radojkovic,
  • Svetlana Apostolovic,
  • Nenad Bozinovic,
  • Snezana Ciric Zdravkovic,
  • Stefan Milutinovic,
  • Bojan Maricic,
  • Nikola Živković,
  • Mladjan Golubovic,
  • Miodrag Djordjevic,
  • Radomir Damjanović,
  • Abraham Bell,
  • Boris Đinđić

Journal volume & issue
Vol. 156
p. 113918

Abstract

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In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 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 CCl4, 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-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. 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 CCl4 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 CCl4 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 CCl4. The hepatoprotective mechanisms in CCl4 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.

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