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.