Pyrroloquinoline quinone protects against doxorubicin-induced cardiotoxicity in mice by modulating Nrf2 and NF-kB activities

Pyrroloquinoline quinone (PQQ) is a potent antioxidant cofactor that is widely distributed in the animal and plant tissues and is considered to be an indispensable nutrient in the mammals. In the present investigation, we examined PQQ effects on doxorubicin (DOX)-induced cardiotoxicity in mice. The animals received a single 15-mg/kg intraperitoneal dose of DOX injection at day 1. A daily oral dose of 10 mg/kg PQQ were administered to the mice in the study group. Nuclear factor kappa beta (NF-kB) and nuclear factor erythroid 2related factor 2 (Nrf2) activities were measured in the nuclear fractions of cardiac tissue homogenates. Cardiac histopathology and function, as well as serum markers of cardiac injury and tissue markers of inflammation and oxidative stress were examined. PQQ improved Nrf2 activity and at the same time suppressed NF-kB activity. PQQ reduced cardiac levels of tumor necrosis factor alpha (TNF alpha) and malondialdehyde (MDA), and elevated tissue activities of superoxide dismutase (SOD). PQQ decreased serum levels of creatinine kinase MB (CK-MB) and cardiac troponin I (cTnI), and improved histopathological indices of cardiac injury as well as cardiac function. Altogether, these findings emphasize that PQQ is protective against DOX-induced cardiotoxicity in mice by modulating NF-kB and Nrf2 pathways.