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

• Published in: Nutrients Vol. 14; no. 4; p. 733
• Main Authors: Sirwi, Alaa, Shaik, Rasheed A, Alamoudi, Abdulmohsin J, Eid, Basma G, Elfaky, Mahmoud A, Ibrahim, Sabrin R M, Mohamed, Gamal A, Abdallah, Hossam M, Abdel-Naim, Ashraf B
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.02.2022; MDPI
• Subjects: 4-Butyrolactone - analogs & derivatives; Animals; Anthracycline; Anti-Inflammatory Agents - therapeutic use; Antibiotics; Antioxidants; Antioxidants - metabolism; Apoptosis; BAX protein; Bcl-2 protein; Calcium-binding protein; Cancer therapies; Carbonyl compounds; Carbonyls; Cardiomyopathy; Cardiotoxicity; Cardiotoxicity - prevention & control; Caspase-3; Catalase; Creatine; Creatine kinase; Dehydrogenases; Depletion; Doxorubicin; Doxorubicin - toxicity; Drug dosages; Electrocardiography; Gene expression; heart; Heart failure; Heme; Heme oxygenase (decyclizing); Inflammation; Injury prevention; Interleukin 6; Kinases; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Malondialdehyde; mokko lactone; Myocardium - metabolism; Natural products; Nuclear transport; Oxidative Stress; Oxygenase; Pharmacy; Rats; Sesquiterpenes - therapeutic use; Superoxide dismutase; Translocation; Troponin; Tumor necrosis factor-TNF; Tumor necrosis factor-α; United Kingdom > UK; United States > US; mokko lactone; heart; doxorubicin
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14040733

Doxorubicin (DOX), a commonly utilized anthracycline antibiotic, suffers deleterious side effects such as cardiotoxicity. Mokko lactone (ML) is a naturally occurring guainolide sesquiterpene with established antioxidant and anti-inflammatory actions. This study aimed at investigating the protective effects of ML in a DOX-induced cardiotoxicity model in rats. Our results indicated that ML exerted protection against cardiotoxicity induced by DOX as indicated by ameliorating the rise in serum troponin and creatine kinase-MB levels and lactate dehydrogenase activity. Histological assessment showed that ML provided protection against pathological alterations in heart architecture. Furthermore, treatment with ML significantly ameliorated DOX-induced accumulation of malondialdehyde and protein carbonyl, depletion of glutathione, and exhaustion of superoxide dismutase and catalase. ML's antioxidant effects were accompanied by increased nuclear translocation of NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. Moreover, ML exhibited significant anti-inflammatory activities as evidenced by lowered nuclear factor κB, interleukin-6, and tumor necrosis factor-α expression. ML also caused significant antiapoptotic actions manifested by modulation in mRNA expression of Bax, Bcl-2, and caspase-3. This suggests that ML prevents heart injury induced by DOX via its antioxidant, anti-inflammatory, and antiapoptotic activities.