Effect of Long-Term Isatin Administration on Daily Physical Activity and Cardiac Performance in Female Rats.

BACKGROUND

Isatin, an endogenous indole found in the brain and peripheral tissues, has a wide spectrum of physiological and pharmacological effects. This study aims to disclose the impact of long-term isatin administration on daily voluntary running, cardiac performance, and the expression of genes and proteins involved in signaling pathways in left ventricular tissue in rats.

METHODS

Wistar Albino rats were housed in standard cages or cages with running wheels for 28 days and received either intraperitoneally saline or isatin at 20 mg/kg/day or isatin 100 mg/kg/day from day 14 until 28. The hearts were perfused with Krebs-Henseleit solution ex vivo to measure developed left ventricular pressure and rate of contraction and relaxation. Protein kinase B (AKT), extracellular signal-regulated kinase1/2 (ERK1/2), and pyruvate dehydrogenase kinase-4 (PDK4) gene and protein expressions were determined in the ventricle.

RESULTS

Isatin did not alter daily running activity, cardiac performance, or AKT gene expression in groups (P > .05 for all). Ventricular weight/body weight and ERK1/2 gene expression were higher in the physically active group administered a high dose of isatin (100 mg/kg/day) than in the inactive group administered the same dose (P = .007, P = .042, respectively). PDK-4 protein level was lower in the physically active group administered a low dose of isatin compared with the inactive control group.

CONCLUSION

Long-term isatin administration is well tolerated in female rats without negatively affecting daily physical activity and ex vivo cardiac performance. In physically active rats, the ERK1/2- and PDK-4-mediated effects of isatin on the left ventricle may differ depending on its dose.