Cobalt protoporphyrin promotes heme oxygenase 1 expression and ameliorates cardiac dysfunction in long-term fasting...

The association between malnutrition and cardiac dysfunction has been reported. Heme oxygenase (HO)-1 played protective roles in the animals functioning as a myocardial infarction, heart failure, or cardiomyopathy model. We hypothesized that the administration of HO-1 inducer, cobalt protoporphyrin (CoPP) reduces oxidative stress and ameliorates cardiac systolic dysfunction in long-term fasting mice.

C57BL/6 J mice were classified into three groups: fed mice (fed group), 48-h fasting mice with a single intraperitoneal injection of the corresponding vehicle (fasting group), and 48-h fasting mice with a single intraperitoneal injection of 5 mg/kg CoPP (CoPP group).

The fasting group showed a significant increase in heme and 4-hydroxy-2-nonenal (4HNE) protein in the heart tissue, and reduced left ventricular ejection fraction (LVEF) when compared with the fed group. The CoPP group showed significantly increased protein levels of nuclear factor-erythroid 2-related factor 2 and HO-1, and increased mRNA expression levels of HO-1, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, forkhead box protein O1, sirtuin-1, cyclooxygenase 2, and superoxide dismutase 2, and reduced levels of heme and 4HNE protein when compared with the fasting group. LVEF were significantly higher in the CoPP group than in the fasting group.

Administration of CoPP reduced heme accumulation and oxidative stress, and ameliorated cardiac systolic dysfunction in long-term fasting mice. This study suggests that heme accumulation may be associated with impaired cardiac function induced by long-term fasting and that HO-1 may be a key factor or therapeutic target.