Lactoferrin (LF) administered enterally increases serum glucagon-like peptide-1 (GLP-1) levels, showing cardioprotective effects against myocardial ischemia-reperfusion (IR) injury in rats. However, the mediation of the effects by enteral LF-induced GLP-1 remains unclear. The aim is to investigate the cardioprotective effects of enteral LF-induced GLP-1 using the GLP-1 receptor antagonist exendin (Ex) (9–39).

Random sampling divided the hearts (n = 32) into four groups: cont (control), LF, contEx, and LFEx. In the cont and LF rats, intravenous saline was administered; saline or LF (1000 mg/kg) was provided by gavage 15 min later. In the contEx and LFEx rats, intravenous Ex (9–39) was administered, followed by saline or LF by gavage 15 min later. The hearts were excised 15 min after the gavage. During heart excision, blood samples were collected to measure serum GLP-1 levels. Hearts were perfused using the Langendorff system for 20 min before 15 min of no-flow ischemia, followed by 20 min of reperfusion. Protein kinase A (PKA) and phospho-protein kinase B (p-Akt) levels in the myocardium were measured using western blotting. The primary outcome was the maximum left ventricular pressure derivative (LV dP/dt max) 10 min after reperfusion.

Enteral LF significantly increased serum GLP-1 levels. LV dP/dt max in the LF group at 45 min (10 min after reperfusion) was significantly higher than that in the cont group. This effect was diminished by Ex (9–39). Western blotting showed that enteral LF significantly activated PKA but not p-Akt.

Enteral LF mitigates myocardial IR via enteral LF-induced GLP-1.