Urolithin A’s Antioxidative, Anti-Inflammatory, and Antiapoptotic Activities Mitigate Doxorubicin-Induced Liver Injury in Wistar Rats

Figures

• 

  Figure 1. Experimental design of the proposed work.

• 

  Figure 2. Effect of URO A on serum biomarkers of hepatotoxicity induced by DOX in rats: (A) AST activity, (B) ALT activity, and (C) GGT activity. Data are presented as mean ± SEM (n = 6); * indicates significantly different at p < 0.05 and **** at p < 0.0001; ns: nonsignificant.

• 

  Figure 3. Representative histopathological examination of hematoxylin-and-eosin-stained photomicrographs of rat livers: (A) Normal liver histology showing no evidence of necrosis or inflammatory cell infiltration. (B) DOX-treated group with intralobular mononuclear inflammatory infiltrations, congestion of pericentral vessels and sinuses, and degeneration of hepatocytes increasing vacuolation in the cytoplasm of hepatocytes and appearing as indistinct, clear vacuoles. (C) DOX with URO A (2.5 mgkg−1) treatment group exhibiting considerable improvement in necrosis, inflammatory cells, and glycogen infiltration. (D) DOX with URO A (5 mgkg−1) treatment group showing marked improvement in vacuolization and inflammatory cells with moderate improvement in necrosis extending from the central zone to the midzone. (E) Semiquantitative pathologic score depending on the severity and tissue damage.

• 

  Figure 4. Effect of URO A on oxidative status in DOX-induced hepatotoxicity in rats: (A) effect on MDA levels, (B) effect on SOD activity, and (C) effect on catalase activity. Data are presented as mean ± SEM (6 rats per group); * p < 0.05; **** p < 0.001; ns: non-significant (one-way ANOVA followed by Holm–Šídák’s multiple comparisons test; p < 0.05).

• 

  Figure 5. Effect of URO A on apoptotic markers in DOX-induced hepatotoxicity in rats: (A) effect on caspase 3 levels and (B) effect on mitochondrial cytochrome c oxidase. Data are presented as mean ± SEM (6 rats per group); * p < 0.05 and **** p < 0.001; ns: non-significant (one-way ANOVA followed by Holm–Šídák’s multiple comparisons test).