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Basic Clin Pharmacol Toxicol. 2019 Oct 19. doi: 10.1111/bcpt.13340. [Epub ahead of print]

β-LAPachone ameliorates doxorubicin-induced cardiotoxicity via regulating autophagy and Nrf2 signalling pathways in mice.

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Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Infectious and Tropical Diseases Research Center, Department of Clinical Biochemistry, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.


β-LAPachone (B-LAP) is a naphthoquinone that possesses antioxidant properties. In the present investigation, the protective effect of B-LAP against doxorubicin (DOX)-induced cardiotoxicity was examined in mice. Thirty-five mice were divided into 5 groups; control group, B-LAP (5 mg/kg) group, DOX (15 mg/kg) group, DOX+B-LAP (2.5 mg/kg) group and DOX+B-LAP (5 mg/kg) group. B-LAP was administered orally for 14 days of experimental period. A single dose of DOX (15 mg/kg) was injected intraperitoneally on day 3. Cardiac function, histoarchitecture, indices of oxidative stress, as well as circulating markers of cardiac injury were examined. B-LAP (5 mg/kg) decreased serum levels of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) and cardiac troponin I (cTnI), and ameliorated cardiac histopathological alterations. In addition to increasing cellular NAD+ /NADH ratio, B-LAP upregulated the cardiac levels of SIRT1, beclin-1, p-LKB1 and p-AMPK, and reduced the cardiac levels of p-mTOR, interleukin (IL)-1β, TNF (tumour necrosis factor)-α and caspase-3. B-LAP also elevated the nuclear accumulation of Nrf2 and simultaneously upregulated the protein levels of heme oxygenase (HO-1) and glutathione S-transferase (GST) in the hearts of DOX mice. While B-LAP reduced malondialdehyde concentrations in heart of DOX-treated mice, it further promoted the activities of cardiac superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT). In accordance with increased cell survival, B-LAP significantly improved the cardiac function of DOX mice. Collectively, these findings underline the protective potential of B-LAP against DOX-induced cardiotoxicity by regulating autophagy and AMPK/Nrf2 signalling pathway in mice.


Cardiotoxicity; Doxorubicin; Mice; Nrf2; β-LAPachone


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