L-theanine abates oxidative stress and mitochondrial dysfunction in myocardial ischemia-reperfusion injury by positively regulating the antioxidant response.

L-theanine (L-THE), a non-protein amino acid isolated from Camelia sinensis, has antioxidant properties that could prevent oxidative damage and mitochondrial dysfunction generated by myocardial ischemia and reperfusion (I/R) injury. The present study aimed to identify the effects of pretreatment with L-THE in rat hearts undergoing I/R. Wistar rats received vehicle or 250 mg/Kg L-THE intragastrically for 10 days. On day 11, hearts were removed under anesthesia and exposed to I/R injury in the Langendorff system. Measurement of left ventricular developed pressure and heart rate ex vivo demonstrates that L-THE prevents I/R-induced loss of cardiac function. Consequently, the infarct size of hearts subjected to I/R was significantly decreased when L-THE was administered. L-THE also mitigated I/R-induced oxidative injury in cardiac tissue by decreasing reactive oxygen species and malondialdehyde levels, while increasing the activity of antioxidant enzymes, SOD and CAT. Additionally, L-THE prevents oxidative phosphorylation breakdown and loss of inner mitochondrial membrane potential caused by I/R, restoring oxygen consumption levels, increasing respiratory control and phosphorylation efficiency, as well as buffering calcium overload. Finally, L-THE modifies the expression of genes involved in the antioxidant response through the overexpression of SOD1, SOD2 and CAT; as well as the transcriptional factors PPARα and Nrf2 in hearts undergoing I/R. In conclusion, L-THE confers cardioprotection against I/R injury by preventing oxidative stress, protecting mitochondrial function, and promoting overexpression of antioxidant genes. More studies are needed to place L-THE at the forefront of cardiovascular research and recommend its therapeutic use.