Protective Effect of Prostaglandin E1 on Renal Microvascular Injury in Rats of Acute Aristolochic Acid Nephropathy

Abstract

Background: To investigate the renal microvascular injury in acute aristolochic acid nephropathy (AAN) and the protective effects of prostaglandin E1 (PGE1) in acute AAN. Methods: Female Sprague-Dawley rats were randomly divided into three groups. The rats in PGE1 group received Caulis Aristolochia manshuriensis (CAM) decoction by gavage for 5 days, and PGE1 was given by vena caudalis before gavage. The rats in model group were gavaged with CAM for 5 days, and the same dose of 0.9% physiologic saline was given by vena caudalis. The rats in control group only received an equal daily volume of saline solution by gavage. Animals were killed at days 3, 5, and 7. Blood urea nitrogen (BUN), serum creatinine, and urinary protein were monitored before killing. Microvascular density was determined by JG12 immunostaining. The expression of angiogenic factor was assessed by vascular endothelial growth factor (VEGF). Tubulointerstitial hypoxia was assessed by hypoxia-inducible factor-1a (HIF-1a) expression. Results: CAM induced a significant decrease in VEGF expression and microvascular density in the kidney tissue, accompanied by a significant increase in HIF-1a, which reduced renal function and increased 24-h urinary protein excretion rates. PGE1 lessened the capillary loss, relieved hypoxia, and protected renal function. No significant pathological changes were found in control rats. Conclusion: The renal microvascular injury in acute AAN is severe. PGE1 can significantly ameliorate the renal microvascular injury, relieve hypoxia, and protect renal function.

Inhibition of insulin resistance by PGE1 via autophagy-dependent FGF21 pathway in diabetic nephropathy

“…However, the onset of these drugs needs at least 4–5 years 23 and the benefit seems limited 24 . Recent studies showed that PGE1 had protective effects on renal function by reducing vascular resistance in ischemia-reperfusion 25 , inhibiting the production of transforming growth factor-β (TGF-β) and interleukin-1 (IL-1) in immune-mediated glomerular disease 26 , and increasing microvessel density in acute toxic renal injury 27 . But it is currently unclear if PGE1 could be used for preventing the progression of DN.…”

“…Our findings provide further evidences that PGE1 contributed to improve renal dysfunction in T2DM patients 48 . The renoprotective role of PGE1 has also been reported extensively in the treatment of ischemic renal reperfusion injury, toxic kidney injury, immune-mediated glomerular injury, and contrast-induced nephropathy, consequently resulting in slow progression of ESRD 27 , 49 – 51 . Thus, the present study provided new mechanisms for renoprotective role of PGE1 in clinical research.…”

Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats

“…The serum creatinine (Scr) was measured using a picric acid method and blood urea nitrogen (BUN) was measured using a urease assay as previously described ( 20 , 21 ). Serum was obtained from blood samples collected in non-heparinized vacuum tubes, then centrifuged at 3,500 x g for 15 min.…”

Aristolochic Acid-Induced Nephrotoxicity: Molecular Mechanisms and Potential Protective Approaches

“…In a Sprague-Dawley rat model of AAN, treatment with PGE1 increased vascular endothelial growth factor (VEGF) expression and microvascular density. PGE1 also prevented capillary loss and relieved hypoxia, resulting in kidney protection against AA-induced nephrotoxicity [110].…”