Protective Role of Menthol Against Doxorubicin-Induced Cardiac Injury Through Suppression of TLR4/MAPK/NF-κB Signaling and Oxidative Stress

Figure 1. Effect of menthol on serum Troponin-1 (A) level. Data were expressed as mean ± S.E.M (n = 10). Menthol was given at a dose (100 mg/kg/p.o./daily) for 7 days. Blood and tissue samples were collected on day 8. Cardiotoxicity was induced by DOX (15 mg/kg, IP, once). Statistical analysis was performed using ANOVA followed by Turkey’s multiple comparison test. (n = 10) a: substantially varied from the control group, b: substantially varied from DOX group at p < 0.05.

Figure 2. Effect of menthol on MDA (A), SREBP1C (B), and GSH (C) contents. Data were presented as mean ± S.E.M (n = 10). Menthol was given at a dose (100 mg/kg/p.o./daily) for 7 days. Blood and tissue samples were collected on day 8. DIC (15 mg/kg, IP, once). Statistical analysis was performed using ANOVA followed by Turkey’s multiple comparison test. a: substantially varied from the control group, b: substantially varied from DOX group at p < 0.05.

Figure 3. Effect of menthol on MAPK (A), TLR4 (B), and PPAR-α (C) contents. Data were expressed as mean ± S.E.M (n = 10). Menthol was given at a dose (100 mg/kg/p.o./daily) for 7 days. Blood and tissue samples were collected on day 8. Statistical analysis was performed using ANOVA followed by Turkey’s multiple comparison test. a: substantially varied from the control group, b: substantially varied from DOX group at p < 0.05.

Figure 4. Photomicrographs of heart tissues showed weak Caspase-3, p53, and NF-κB expression in control and menthol groups. The DOX group exhibited severe p53 but moderate Caspase-3 and NF-κB expression, while the DOX + menthol group revealed weak, near-normal expression (DAB, ×400). Values are mean ± SEM at p <0.05. a: substantially varied against control, b: substantially varied against DOX group.

Figure 5. The photomicrographs show the cardiac tissue from various groups of experiments. The control group shows normal myocardium. In contrast, the DOC group reveals myocardial necrosis with fragmentation (blue arrows), infiltration of mononuclear cells (black arrow) at both magnifications, and congested blood vessels (*). The DOX + menthol group showed small focal aggregations of mononuclear inflammatory cells (arrows) at both magnifications and apparently normal myocardium. The menthol-alone group exhibits clearly normal myocardium. (H&E, ×400).

Figure 6. Graphical abstract illustrates the pathway for DIC through crosstalk between CAMP, PI3K/AKT, and FOXO.1, PTP.1B /p53/caspase-3.