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The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an l-NAME model of pre-eclampsia

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Abstract

We investigated the effects of sildenafil citrate (SC) on podocyturia in N ω-nitro-l-arginine methyl ester hydrochloride (l-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague–Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of l-NAME in drinking water for 4–8 days for EOPE and 8–14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of l-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.

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Acknowledgements

The authors would like to extend our deepest gratitude to Ms. K. Moodley, Dr. S.D. Singh, Dr. L. Bester and the staff of the Biomedical Resource Unit for technical assistance with the animal study. This project was funded by the National Research Foundation, South Africa (Grant Number: 91544).

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Authors and Affiliations

  1. Department of Human Physiology, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa

    Sooraj Baijnath, Saravanakumar Murugesan & Irene Mackraj

  2. Department of Family Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    Prem Gathiram

  3. Department of Obstetrics and Gynaecology and Women’s Health and HIV Research Group, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

    Jagidesa Moodley

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  1. Sooraj Baijnath
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  2. Saravanakumar Murugesan
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  5. Jagidesa Moodley
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Correspondence to Saravanakumar Murugesan or Irene Mackraj.

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Baijnath, S., Murugesan, S., Mackraj, I. et al. The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an l-NAME model of pre-eclampsia. Mol Cell Biochem 427, 59–67 (2017). https://doi.org/10.1007/s11010-016-2897-5

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