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

Abstract

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.

Keywords: Isatin; cardiac hypertrophy; extracellular-regulated kinase 1, 2; natriuretic peptide; voluntaryrunning.

Figure 1.

Study design. IBW, Initial body weight; FBW, Final body weight; C-V, control-vehicle; C-IL, control-isatin-low-dose; and C-IH, control-isatin-high-dose. PA-V, physical activity-vehicle; PA-IL, physical activity-isatin-low-dose; PA-IH, physical activity-isatin-high-dose groups.

Figure 2.

Effect of low- and high-dose isatin administration on heart rate and cardiac contractility of ex vivo perfused hearts, and cGMP concentration in the perfusate collected during the 15-minute perfusion; C-V, control-vehicle (n = 6); C-IL, control-isatin-low-dose (n = 5); C-IH, control-isatin-high-dose (n = 5); PA-V, physical activity-vehicle (n = 6); PA-IL, physical activity-isatin-low-dose (n = 3); PA-IH, physical activity-isatin-high-dose (n = 4) groups. Values are expressed as mean ± SD. ^*P < .05, ^***P < .001.

Figure 3.

Effect of low- and high-dose isatin administration on the protein kinase B (AKT), extracellular-regulated kinase 1/2 (ERK1/2), pyruvate dehydrogenase kinase-4 (PDK-4), and B-type natriuretic peptide (BNP) gene expressions in left ventricle tissue in C-V, control-vehicle (n = 7); C-IL, control-isatin-low-dose (n = 7); C-IH, control-isatin-high-dose (n = 7); PA-V, physical activity-vehicle (n = 6); PA-IL, physical activity-isatin-low-dose (n = 6); and PA-IH, physical activity-isatin-high-dose (n = 6) groups. Values are expressed as mean ± SD. ^*P < .05.

Figure 4.

Effect of low and high dose isatin administration on the protein kinase B (AKT), extracellular-regulated kinase 1/2 (ERK1/2), pyruvate dehydrogenase kinase-4 (PDK-4) protein expressions in left ventricle tissue in the C-V, control-vehicle (n = 7); C-IL, control-isatin-low-dose (n = 7) and C-IH, control-isatin-high-dose (n = 7); PA-V, physical activity-vehicle (n = 6); PA-IL, physical activity-isatin-low-dose (n = 6); PA-IH, physical activity-isatin-high-dose (n = 6) groups. Values are expressed as mean ± SD. ^*P< .05.