The treatment of preeclampsia in a rat model employing Digibind.
Preeclampsia (PE) is a disorder that results in significant fetomaternal morbidity and mortality with yet no definitive pharmacological intervention. It involves the development of de novo hypertension and proteinuria after 20 weeks of pregnancy. All too often, intrauterine growth restriction (IUGR) occurs. Evidence has accrued that implicates the cardiac glycosides (the cardenolides and the bufadienolides) as potentially involved in the pathophysiology of PE. These compounds act by inhibiting Na(+)/K(+) ATPase. Digibind (digoxin immune Fab) antagonizes this action of the cardenolides. It also has cross-reactivity against the bufadienolides, including marinobufagenin. This study investigated the effects of Digibind in a rat model of PE. We induced a syndrome in rats, which includes many of the phenotypic characteristics of human PE. Digibind, in escalating doses, was given on days 10 to 20 of pregnancy. Digibind produced significant lowering of the blood pressure and reduced proteinuria in our rat model of PE. However, it also did not avert IUGR. In view of these findings, in our experimental model of human PE, further studies in the quest for effective treatment of PE need to focus on pharmaceuticals that can remedy the syndrome without compromising the fetus.
Agunanne
Enoch
E
The Nephrology/Hypertension Division, Department of Medicine, Texas A&M Health Science Center/Scott & White, Temple, Texas 76508, USA.
Horvat
Darijana
D
Uddin
Mohammad N
MN
Puschett
Jules
J
D000818:Animals; D000831:Animals, Newborn; D001795:Blood Pressure Determination; D002018:Bufanolides / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced / Q000503:physiopathology; D007140:Immunoglobulin Fab Fragments / Q000009:adverse effects / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000188:drug therapy*; D011247:Pregnancy; D011270:Pregnancy, Animal; D011336:Probability; D011507:Proteinuria; D011897:Random Allocation; D051381:Rats; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome; D016482:Urinalysis
D002018:Bufanolides; D007140:Immunoglobulin Fab Fragments; C050199:digoxin antibodies Fab fragments; C093896:marinobufagenin