Mokko Lactone Alleviates Doxorubicin-Induced Cardiotoxicity in Rats via Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities

Figure 1. Effect of ML on DOX-induced on ECG patterns: (A) control group; (B) DOX group; (C) DOX + ML (15 mg/kg); and (D) DOX + ML (30 mg/kg), DOX = Doxorubicin, ML = Mokko Lactone.

Figure 2. Effect of ML on DOX-induced histopathological changes on cardiac tissues: (A) control group demonstrating normal architecture of the heart tissues; (B) DOX group exhibiting mononuclear inflammatory cells infiltration and widespread necrosis of cardiac tissues (black arrow); (C) DOX + ML (15 mg/kg) treated group showing limited inflammatory areas and degenerated cardiomyocytes; (D) DOX + ML (30 mg/kg) treated group with restoration of a nearly normal cardiac histology. DOX = Doxorubicin, ML = Mokko Lactone.

Figure 3. Effect of ML on serum cardiac markers in DOX-treated rats: (A) serum troponin level; (B) serum CK-MB level; (C) serum LDH activity. Background dotted lines represent range of corresponding control values. Data are displayed as mean ± SD (n = 6). DOX = Doxorubicin, ML = Mokko Lactone. a, significantly different than control (p < 0.05); b, significantly different than DOX (p < 0.05); c, significantly different than DOX + ML (15 mg/kg) (p < 0.05).

Figure 4. Effect of ML on oxidative status of on DOX-induced cardiotoxicity in rats: (A) cardiac MDA content; (B) cardiac CAT activity; (C) cardiac SOD activity; (D) cardiac GSH; and (E) cardiac protein carbonyl content. Data are displayed as mean ± SD (n = 6). DOX = Doxorubicin, ML = Mokko Lactone. a, significantly different compared with control (p < 0.05); b, significantly different compared with DOX (p < 0.05); c, significantly different compared with DOX + ML (15 mg/kg) (p < 0.05).

Figure 5. Effect of ML on Nrf2 expression as determined immunohistochemically (A–E) and mRNA expression of Nrf2 (F) and HO-1 (G) in cardiac tissues of DOX-treated rats. Data shown as bar charts are mean ± SD (n = 6). DOX = Doxorubicin, ML = Mokko Lactone. a, b, or c: statistically different from control, DOX, or DOX + ML (15 mg/kg), respectively (p < 0.05).

Figure 6. Effect of ML on NFκB, IL-6, and TNF-α, as determined by immunohistochemistry (A) or ELISA (B) in cardiac tissues of DOX-treated rats. Data in bar charts are mean ± SD (n = 6). DOX = Doxorubicin, ML = Mokko Lactone. a, b or c: statistically significant compared with control, DOX, or DOX + ML (15 mg/kg), respectively (p < 0.05).

Figure 7. Effect of ML on cardiac mRNA expression of Bax (A), Bcl-2 (B), and caspase-3 (C) in DOX-treated rats. Data shown in bar charts are mean ± SD (n = 6). DOX = Doxorubicin, ML = Mokko Lactone. a, b or c: statistically significant compared with control, DOX, or DOX + ML (15 mg/kg), respectively (p < 0.05).