Pharmaceutical Regulatory Affairs

Biography

Biography: Hayam I Gad

Abstract

Introduction: Investigate the potential role of anti TNF- antibodies on some renal functions and release of vasoregulatory peptides using nitric oxide synthase deprived pregnant rats. Methods: The study was carried out at King Khalid university Hospital, King Saud University, Riyadh. Forty female Wistar rats were divided into four groups (10 rats each); Group I: Included virgin non-pregnant rats. Groups II: Included pregnant rats that received saline, gropuIII included pregnant rats that received NG-nitro- L- arginine methyl ester (L-NAME) while group IV included pregnant rats that received both L-NAME and anti TNF- antibodies respectively. Treatment of pregnant rats started from day 7 up to day 20 of gestation.Mean arterial blood pressure, urine volume, creatinine clearance and 24 hours urinary albumin excretion were measured on day20 of gestation. Blood samples were taken on day 20 of gestation for measurement of plasma endothelin-1 (ET-1), angiotensin II (Ag II) and serum levels of total nitric oxide (NO) products, interleukin-6 (IL-6) and soluble vascular cell adhesion molecule (sVCAM-1). Viable pups were also weighed. Results: Treatment of pregnant rats with anti TNF-α antibodies restored the urine volume, creatinine clearance, the plasma ET-1, the serum IL-6, and the serum sVCAM-1 to normal levels on day 20 of gestation. However, it showed no effect regarding serum NO. Also pup weight was insignificantly changed in anti TNF-α antibodies treated rats when compared to non treated pregnant rats. In fact administration of anti TNF-α antibodies to rats from day 7 up to day 20 of gestation decreased significantly the 24 hour urinary albumin excretion and the plasma Ag II when compared to L-NAME treated rats but still showed significant increase as compared to controls (P<0.001). Conclusion: Preeclampsia is associated with disturbed renal function, overproduction of cytokines and vasoregulatory factors, and fetal growth restriction. Treatment of pregnant rats with anti TNF-α antibodies restored urine volume, creatinine clearance, plasma ET-1, serum IL-6 and sVCAM-1 to normal levels. Hence, anti TNF-α antibodies may have beneficial effects in preeclampsia. Additional studies are warranted to confirm these results.