Syringic acid pretreatment potentiates antioxidant mechanism and downregulates inflammatory signaling towards doxorubicin-related oxidoinflammatory hepatorenal damage in rats

Fig. 1. (A-D). Effect of oral SA pretreatment on LPO and antioxidant profile in the liver DOX-treated rats. Each bar represents the mean ± SD of 6 rats. The significance level was set at p < 0.05. DOX: doxorubicin; SA: syringic acid; MDA: malondialdehyde; GSH: glutathione; SOD: superoxide dismutase; CAT: catalase.

Fig. 2. (A-D). Effect of oral SA pretreatment on LPO and antioxidant profile in the kidney DOX-treated rats. Each bar represents the mean ± SD of 6 rats. The significance level was set at p < 0.05. DOX: doxorubicin; SA: syringic acid; MDA: malondialdehyde; GSH: glutathione; SOD: superoxide dismutase; CAT: catalase.

Fig. 3. Effect of oral SA pretreatment on serum 8-OHdG levels in DOX-treated rats. Each bar represents the mean ± SD of 6 rats. The significance level was set at p < 0.05. DOX: doxorubicin; SA: syringic acid; 8-OHdG: 8-hydroxy-2’ -deoxyguanosine.

Fig. 4. (A-D). Effect of oral SA pretreatment on hepatic and renal function parameters in the serum DOX-treated rats. Each bar represents the mean ± SD of 6 rats. The significance level was set at p < 0.05. DOX: doxorubicin; SA: syringic acid; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen; Cre: creatinine.

Fig. 5. (A-G). The liver’s representative photographic section from control, SA alone, DOX alone, and DOX + SA experimental rats. Control (A) and SA (B) alone indicate no important lesion, characterized by structurally and functionally normal hepatocytes. The hepatic structure of rats administered with DOX alone demonstrated severe mononuclear cell infiltration in the periportal areas (bold arrow), severe necrosis (arrow), and moderate hydropic degeneration (arrowhead) (C). The morphological attributes of the liver treated with SA + DOX appeared to be improving with mild mononuclear cell infiltration in the periportal areas (bold arrow), moderate necrosis (arrow), and mild hydropic degeneration (arrowhead) (D). Histopathological scores (E–G). Each bar represents the mean ± SD. Hematoxylin and Eosin stained, DOX: doxorubicin; SA: syringic acid.

Fig. 6. (A-F). The kidney’s representative photographic section from control, SA alone, DOX alone, and DOX + SA experimental rats. Control (A) and SA (B) alone indicate no important lesion. The renal structure of rats administered with DOX alone demonstrated severe mononuclear cell infiltrations in the interstitial areas (arrow) and severe tubular degeneration (asterisk) (C). The morphological attributes of the kidney treated with SA + DOX appeared to improve with mild mononuclear cell infiltration in the interstitial areas (arrow), and mild tubular degeneration (asterisk) (D). Histopathological scores (E–F). Each bar represents the mean ± SD. Hematoxylin and Eosin stained, DOX: doxorubicin; SA: syringic acid.

Fig. 7. (A-D). Effect of SA on TNF-α and IL-6 mRNA expression levels in the liver and kidney of DOX-treated rats. Each bar represents the mean ± SD of 6 rats. The significance level was set at p < 0.05. DOX: doxorubicin; SA: syringic acid; TNF-α: tumour necrosis factor-alpha; IL-6: interleukin-6.

Fig. 8. (A-J). Immunohistochemical analysis of TNF-α and IL-6 in the liver tissues of experimental groups. Scale bar = 50 µm. (A-D): Immunnegativity in control (A, B) and SA-only treated (C, D) groups. (E–F): DOX group. Severe TNF-α and moderate IL-6 immunopositivity (arrows). (G-H): SA + DOX group. Mild TNF-α and mild IL-6 immunopositivity (arrows). (I, J): Immunohistochemical score. Each bar represents the mean ± SD. DOX: doxorubicin; SA: syringic acid; TNF-α: tumour necrosis factor-alpha; IL-6: interleukin-6.

Fig. 9. (A-J). Immunohistochemical analysis of TNF-α and IL-6 in the kidney tissues of experimental groups. Scale bar = 50 µm. (A-D): Immunnegativity in control (A, B) and SA-only treated (C, D) groups. (E–F): DOX group. Severe TNF-α and moderate IL-6 immunopositivity (arrows). (G-H): SA + DOX group. Mild TNF-α and moderate IL-6 immunopositivity (arrows). (I, J): Immunohistochemical score. Each bar represents the mean ± SD. DOX: doxorubicin; SA: syringic acid; TNF-α: tumour necrosis factor-alpha; IL-6: interleukin-6.