Dual therapy with allicin and metformin provides superior cardioprotection against doxorubicin-induced cardiotoxicity in rats compared to monotherapy

Figures

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  FIGURE 1. Allicin, metformin, and their combination as modulators of body and relative heart weights in doxorubicin-induced cardiotoxicity in rats statistical analysis for body weight (A) was performed using two-way repeated-measures ANOVA (time × treatment) followed by Tukey’s post hoc test. Relative heart weight (B) was analyzed using one-way ANOVA followed by Tukey’s post hoc test. Data are presented as mean ± SD (n = 10). *p < 0.05 vs. control group.

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  FIGURE 2. Allicin, metformin, and their combination attenuate cardiac enzyme alterations in a rat model of doxorubicin-induced cardiotoxicity. (A) Creatine kinase-MB (CK-MB), (B) lactate dehydrogenase (LDH), and (C) cardiac troponin I (cTn-I). Data are presented as mean ± SD (n = 10). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05 vs. control group, #p < 0.05 vs. DOX group.

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  FIGURE 3. Ameliorative role of allicin, metformin, and their combination on antioxidant biomarkers in doxorubicin-induced cardiotoxicity in rats. (A) Glutathione reductase (GSH), (B) Glutathione peroxidase (GPx), (C) Superoxidase dismutase, (D) Catalase (CAT). Data are presented as mean ± SD (n = 10). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05 vs. control group, #p < 0.05 vs. DOX group, $p < 0.05 vs. DOX + Allicin group, @p < 0.05 vs. DOX + MET group.

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  FIGURE 4. Allicin, metformin, and their combination reduce lipid peroxidation (MDA levels) in a rat model of doxorubicin-induced cardiotoxicity. Data are presented as mean ± SD (n = 10). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05 vs. control group, #p < 0.05 vs. DOX group, $p < 0.05 vs. DOX + Allicin group.

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  FIGURE 5. Allicin, metformin, and their combination restore nitric oxide levels in a rat model of doxorubicin-induced cardiotoxicity. Data are presented as mean ± SD (n = 10). Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. *p < 0.05 vs. control group, #p < 0.05 vs. DOX group, $ p < 0.05 vs. DOX+ Allicin group.

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  FIGURE 6. Histological photomicrographs of cardio sections of tissue from experimental rats were stained with Hematoxylin and Eosin (H&E), showing: (A) Normal Control Group showed: The myocardial architecture was well-preserved, with regular, parallel alignment of cardiac muscle fibers. There were no signs of cellular infiltration, necrosis, or interstitial edema [400×] Scale bar (50 µm). (B) Doxorubicin (DOX)-Treated Group showed: pathological alterations. These included widespread degeneration (Green arrow); a moderate nuclear pyknosis (Yellow arrows); inflammatory cell infiltration (Black arrows); cytoplasmic vacuolization (Blue arrow) and necrosis cells (N) and moderate of cardiac fibers fragmentation (Red arrow); were observed [400×] [100×] Scale bars (50 µm). (C) Doxorubicin (DOX) + Allicin Group showed: moderate histological improvement compared to the DOX-only group. Partial restoration of fiber alignment and some structural alterations persisted, such as a few scattered inflammatory cells (Blue arrow) were observed; pyknotic nuclei (Black arrows); necrosis cells (N); and loss of myocardial cellular constituents (Black circle) [400×] Scale bars B= (50 µm). (D) Doxorubicin (DOX) +…