Bevacizumab-treated pregnant rats may constitute an experimental model for studying preeclampsia.
Abstract
INTRODUCTION: To develop a rat model of preeclampsia by administering
bevacizumab, an angiogenesis inhibitor.
METHODS: Sixteen pregnant rats were randomly allocated to intraperitoneal
injection of 10 mg/kg bevacizumab or 0.1 cc intraperitoneal serum physiologic
on the 4th and 8th days of gestation. Blood pressure, body weight, and
proteinuria were measured on both day 0 (D0) and day 20 (D20). Blood samples
were collected on D20 for analysis, including for determining vascular
endothelial growth factor (VEGF) and soluble Fms-like tyrosine kinase 1
(sFlt-1) levels. On the same day, the mice were euthanized, the placentas and
pups were weighted, and the angiogenesis markers and microvessel density were
evaluated using immunohistochemical methods.
RESULTS: Lower serum VEGF (p = 0.038) and higher SFlt-1 (p = 0.015) levels were
observed in bevacizumab-treated pregnant rats. Bevacizumab-treated pregnant
rats had significantly higher systolic (p = 0.050) and diastolic (p = 0.046)
blood pressures compared to the controls. Additionally, the bevacizumab group
showed a significant increase in proteinuria on D20 compared to that on D0 (p =
0.026). Although higher serum AST, ALT, BUN, and creatinine levels and renal
glomerular endotheliosis scores as well as lower placental VEGF and microvessel
density were noted in bevacizumab-treated rats, these differences were not
statistically significant (p > 0.05 for each).
DISCUSSION AND CONCLUSION: The promising results of this trial show that
bevacizumab treatment in pregnant rats might provide a model to study human
preeclampsia
Keywords
References
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