Cardiac oxidative damage and mitochondrial dysfunction induced by manganese deficiency are probably associated with the inhibition of the Nrf2 signaling pathway.

Manganese is an essential trace element for the human body, yet its role in heart function remains inadequately understood, this study aimed to reveal the influence of Mn deficiency on the heart, and uncover underlying mechanisms involved. A manganese-deficient diet was provided to weaned mice, to which manganese chloride (MnCl2) was administered intraperitoneally to correct Mn deficiency. The pathological changes in the heart were evaluated through histological examination. Cardiac oxidative stress levels were assessed using flow cytometry and biochemical assay kits. The adenosine triphosphate (ATP) content and the levels of mitochondrial respiratory chain (MRC) complexes I-IV were measured with biochemical assay kits. Real-time PCR and Western blotting were performed to determine protein expression related to the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Mn deficiency induced significant cardiac structural damage and elevated serum levels of cardiac injury markers. It also promoted oxidative stress and compromised antioxidant defenses. Mitochondrially, Mn deficiency impaired function, evidenced by reduced ATP levels and suppressed activities of MRC complexes I-IV. Crucially, Mn deficiency inhibited the Nrf2 pathway, demonstrated by decreased Nrf2, HO-1, and NQO1 expression and increased Keap1 expression. However, MnCl2 supplementation significantly improved these alterations. Research results indicated the association of myocardial damage caused by Mn deficiency with mitochondrial dysfunction and oxidative damage, both of which show close correlations with the Nrf2 signaling pathway.