Assessment of Genotoxicity of Levosimendan in Human Cultured Lymphocytes

Abstract

Background and Objective: Levosimendan is a positive inotropic and a vasodilator agent with pleotropic characteristics that include antioxidation, anti-inflammation and smooth muscle vasodilation. Methods: In this study, the effects of levosimendan (0, 0.1, 1, 10, and 20 µg/ml) on oxidative DNA damage and sister-chromatid exchanges (SCEs) were evaluated in human cultured lymphocytes. Results: The results showed that levosimendan increased the frequency of SCEs in all examined concentrations (P<0.01) except for 0.1 µg/ml. On the other hand, levosimendan did not induce oxidative DNA damage as measured by the 8-OHdG biomarker (P > 0.05). In addition, neither mitotic arrest nor proliferation index was affected by levosimendan at all examined doses (P > 0.05). Conclusion: In conclusion, levosimendan might be associated with increases in sister-chromatid exchanges in cultured human lymphocytes. In vivo studies are required to confirm the present findings.

Ameliorative effect of metformin on methotrexate-induced genotoxicity: An in vitro study in human cultured lymphocytes

“…Each sample of freshly drained blood (1 ml) was mixed with 9 ml culture medium (PB-MAX™ Karyotyping Medium; Gibco; Thermo Fisher Scientific, Inc.). PB-Max (Gibco; Thermo Fisher Scientific, Inc.) is an optimized fully supplemented RPMI-1640 medium that includes 15% FBS, L-glutamine and phytohaemagglutinin (a mitogen that stimulates the division of blood lymphocytes) (10,(27)(28)(29).…”

“…477-30-5; Sigma-Aldrich; Merck KGaA) was added to arrest mitosis at the metaphase stage. The procedure of human lymphocyte cell culture preparation was performed according to previously published protocols (10,29,32).…”

“…Chromosomes in the M3 phase were differentiated by exhibiting a combination of differentially stained chromatids, whereas chromosomes in the M4 phase had both chromatids lightly stained (10). To perform the cell kinetics analysis, the proliferative index (PI) was calculated via scoring 100 metaphases from each donor using the following formula: (1 x M1 + 2 x M2 + 3 x ≥M3)/100; where M1, M2 and M3 represent the number of cells at the first, second and third metaphases, respectively (29).…”