Spermicidal Activity of Oxovanadium: DISCUSSION(4)
In sperm, an NADPH-depen-dent superoxide-generating system has been demonstrated. In addition, the ability of H2O2 generating Lactobacillus acidophilus, which is present in the vaginas of most normal women, can further potentiate the spermicidal activity of intravaginally applied oxovanadium(IV) complex. This is in contrast to the commercial vaginal detergent spermicide, N-9, which is selectively toxic to Lactobacilli. Furthermore, unlike N-9, the spermicidal activity of the oxovanadium(IV) complexes was not concomitantly associated with membrane disruption. buy cheap antibiotics
We ascribe the irreversible nature of the sperm-immobilizing activity of oxovanadium(IV) complexes to their ability to induce apoptosis. We used three independent methods that quantitatively assess apoptotic changes in the mitochondria, surface membrane, and nuclear compartment. Mitochondria are the primary targets for apoptosis, and alterations in mitochondrial structure and function are early events of apoptotic cell death. Our studies demonstrated that spermicidal oxovanadium(IV) complexes induced depolarization of sperm mitochondria, an early marker for apoptotic cell death. Prolonged exposure of sperm to these spermicidal complexes also resulted in increased FITC-Annexin V binding to sperm surface due to membrane changes during apoptosis, as well as increased dUTP incorporation in the nuclei of treated sperm. Since vana-dium(IV) compounds by themselves do not cleave DNA, the dramatic uptake of dUTP observed in our study appears to be due to the cleavage of the DNA polymer as a result of cytotoxicity induced by ROS-mediated effects of oxovanadium(IV) complexes. The fact that human sperm are exquisitely sensitive to oxidative stress, and the ability of oxovanadium(IV) complexes to potentiate these effects establishes these oxovanadium(IV) complexes as a new class of gentle contraceptive agents. In addition, our unpublished observations indicate that some of these oxova-nadium(IV) complexes selectively inhibit the growth of human testicular cancer cells via the induction of apoptosis. This activity profile indicates that oxovanadium(IV) complexes could be useful as male antifertility agents as well as anticancer agents against testicular germ cell tumors.