In Vivo and in Vitro Study of the Effect of the Anti-Asthmatic Drug Montelukast on DNA and Activity of Free Radical Scavenging Enzymes

Abstract

This work aimed to investigate the potentiality of Montelukast to alter DNA and the activity of free radical scavenging enzymes (FRSE) in mammalian blood serum and mice liver tissues. DNA was extracted from Balb/c mice pretreated with different concentrations of Montelukast (1.25, 2.5 and 5.0 mg/kg body weight (BW)) and human blood treated with (2.5, 5.0 and 10.0) µg/ml solution to examine the effects of Montelukast in vivo and in vitro, respectively. DNA damage was assessed using gel electrophoresis of S1-nuclease digested DNA to detect the presence of single strand breaks. To determine the effect of Montelukast on FRSE, the activity of glutathione s-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) was measured in liver tissue and serum from Balb/c mice and in human blood treated with Montelukast as described above. Our investigation has shown that Montelukast may possess an indirect effect on DNA that is associated with decreased FRSE activity; the treatment was not associated with increased numbers of ss-breaks (single-strand breaks) in DNA in vivo or in vitro. However, GST, SOD, and CAT activity was significantly decreased compared to the untreated control (p < 0.05) in liver tissue in vivo from mice treated with 2.5 and 5.0 mg/kg BW Montelukast and in human tissue treated with 5 and 10.0 µg/ml Singular. Meanwhile, the enzymatic activity in vitro was significantly decreased (p < 0.05) in GST, SOD and CAT either mouse or human blood serum with increasing the concentration of Montelukast in liver tissue.