A study on the inhibition of rat myocardium glutathione peroxidase and glutathione reductase by moniliformin.

In preparations of Wistar rat myocardium, Km values of GSH-Px to the substrates, H2O2 and GSH, as determined by the DTNB method, were 1.9 x 10(-4) mol/L and 2.0 x 10(-3) mol/L respectively. The Km value of GSSG-R to GSSG was 6.0 x 10(-5) mol/L by UV spectrophotometric assay. In vitro, the activity of GSH-Px was inhibited by 1.0, 6.0 and 16.0 mmol/L synthetic moniliformin (MF) with the corresponding activities of 89.4%, 65.2% and 47.9% of control values (n = 6). The activities of GSSG-R in the presence of 16.0 and 32.0 mmol/L MF were 74.4% and 61.9% of controls (n = 5) respectively. These results revealed that the inhibition of GSH-Px by MF was stronger than that of GSSG-R. As determined by Lineweaver-Burk and of Dixon plots, the inhibition of GSH-Px and GSSG-R by MF was competitive and noncompetitive, respectively. The affinity of GSH-Px to MF was higher than that of GSSG-R because the inhibition constant Ki of the former (6.0 mmol/L) was less than that of the latter (39 mmol/L). We suggest that the mechanism of toxic-damaging effects of MF on myocardium, may be closely related to the failure of remove of free radicals by some enzymes, as GSH-Px and GSSG-R, and that MF may be involved in keshan disease.