Moringa oleifera Leaves Extract Ameliorates Doxorubicin-Induced Cardiotoxicity via Its Mitochondrial Biogenesis Modulatory Activity in Rats

Figures

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  Figure 1. Experimental procedure of doxorubicin-induced cardiotoxicity treated with Moringa oleifera leaves extract. Group 1 (normal) was injected with NaCl once weekly for four (4) weeks and given the vehicle (1% CMC) every 28 days, except on the injection day. Group 2 (Dox) was injected with Doxorubicin once weekly for four weeks (the total dose was 16 mg/kg BW) and given the vehicle (1% CMC) every day for 28 days, except on the injection day. Group 3 (Dox + MO 200) was injected with Doxorubicin once weekly for four (4) weeks (the total dose was 16 mg/kg BW) and given the Moringa oleifera aqueous leaves extract 200 mg/kg BW every day for 28 days, except on the injection day. Group 4 (Dox + MO 400) was injected with Doxorubicin once weekly for four (4) weeks (the total dose was 16 mg/kg BW) and given the Moringa oleifera aqueous leaves extract 400 mg/kg BW every day for 28 days, except on the injection day.

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  Figure 2. Plasma CK-MB (A) and LDH (B) activities in rats after treatment of doxorubicin or doxorubicin with Moringa oleifera leaves extracts.

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  Figure 3. (A) Histopathological of the rats’ cardiac tissues stained with Hematoxylin-Eosin after treatment of doxorubicin or doxorubicin with Moringa oleifera leaves extracts; (B) Score of cardiac tissues’ abnormalities using modified Gibson-Corley’s criteria. The levels of myocarditis were classified as 0 (none, very little), +1 (mild), +2 (moderate), or +3 (severe). Bar = 50 μm. The normal group showed normal histological features, such as normal cardiac muscle fiber arrangement and no inflammatory cell infiltration. The doxorubicin group showed acute cardiotoxicity characterized by myocarditis. Reduced cardiac muscle cell size, foci of necrotizing myocarditis characterized by inflammatory cell infiltration, myocardial necrosis, and bleeding between myocardial fibers were observed. Both treatment groups (MO-200 and MO-400) showed nearly normal structure, little inflammatory cell infiltration, and no bleeding between myocardial fibers.

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  Figure 4. mRNA expressions of Caspase-3/β-actin in rats after treatment of doxorubicin or doxorubicin with Moringa oleifera leaves extracts.

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  Figure 5. (A) 8-hydroxy-2’-deoxyguanosine concentration, (B) malondialdehyde concentration, (C) glutathione peroxidase from cardiac tissues of rats after treatment of doxorubicin or doxorubicin with Moringa oleifera leaves extracts.

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  Figure 6. mRNA expressions of PGC-1α/β-actin (A); PGC-1α/β-actin (B); SOD2/β-actin (C) and mtDNA/nDNA copy number (D) in rats after treatment of doxorubicin or doxorubicin with Moringa oleifera leaves extracts.

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  Figure 7. Proposed mechanism of Moringa oleifera (MO) leaves extract in doxorubicin-induced cardiotoxicity. The beneficial effect of MO is facilitated through its ability to restore the degrees of apoptosis and regulate mitochondrial biogenesis. This is evidenced by normalizing mitochondrial DNA copy number and mRNA expressions of PGC-1α and Nrf2, reducing oxidative stress and DNA damage in cardiac tissue.