TOCOLYTIC EFFECT OF MAGNESIUM-SULFATE AND OR URINARY TRYPSIN-INHIBITOR AGAINST LIPOPOLYSACCHARIDE-INDUCED PRETERM DELIVERY IN MICE/

Background. The purpose of this investigation was to evaluate the effe ct of magnesium sulfate (magnesium) alone or along with urinary trypsi n inhibitor (UTI) in a mouse model in the prevention of preterm delive ry. Methods. On day 17 of pregnancy, female C3H/HeN mice impregnated b y male B6D2F(1) mice were given two intraperitoneal injections of lipo polysaccharide (LPS; 50 mu g/kg) at a 3-hour interval, which treatment induced a 100% incidence of preterm delivery within 25 hours of the s econd dose. Magnesium (4, 5, 6, 7, or 8 mg/hr, sc), UTI (25 x 10(4) un its/kg, ip), magnesium (5 mg/hr, sc) plus UTI(25 x 10(4) units/kg, ip) , saline solution (0.3 ml/hr, sc), or saline solution (0.1 ml/hr, sc a nd 2.5 ml/kg, ip) was administered to pregnant animals on day 18 of ge station. UTI was intraperitoneally given 5 times at 2-hour intervals f rom 8:00 am to 4:00 pm, and magnesium was infused subcutaneously and c onstantly from 8:00 am to 6:00 pm. In addition, the preventive effect of magnesium on LPS-induced contraction of uterine muscle strips and t hat of magnesium, UTI, or magnesium plus UTI on LPS-induced calcium in flux in uterine smooth muscle cells were examined using muscle tissue isolated from pregnant mice on day 17 of gestation. Results. The incid ence of preterm delivery decreased significantly in a dose-dependent f ashion with magnesium treatment, and there was a significant and syner gistic decrease after combined treatment with magnesium plus UTI. The in vitro uterine contraction and calcium influx induced by LPS were si gnificantly suppressed by magnesium. The latter was significantly supp ressed by UTI and additively reduced by magnesium plus UTI. Conclusion s. Combination therapy with magnesium plus UTI may possibly be helpful for preventing preterm delivery in humans without the severe side eff ects induced by hypermagnesemia.