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Low doses of folic acid can reduce hyperhomocysteinemia-induced glomerular injury in spontaneously hypertensive rats

Hypertension Research volume 43, pages 1182–1191 (2020)Cite this article

Abstract

Hypertension associated with hyperhomocysteinemia (HHcy) is associated with a high risk of vascular diseases. However, the mechanisms of HHcy-associated hypertensive renal damage and the efficacy of folic acid (FA) as a treatment have not been fully elucidated. The aim of the present study was to evaluate whether lowering the plasma homocysteine (Hcy) level using different doses of FA can reduce HHcy-associated glomerular injury in spontaneously hypertensive rats (SHRs) and to clarify the potential mechanisms of such effects. SHRs were randomized into a control group, HHcy group, HHcy + low-dose FA (LFA) group, and HHcy + high-dose FA (HFA) group. Compared with the control group, the HHcy group had reduced serum superoxide dismutase and GFR levels and elevated serum malondialdehyde and urinary albumin creatinine ratio levels. Increased extracellular matrix of the glomerulus and an increased glomerular sclerosis index, podocyte foot process effacement and fusion, as well as increased podocyte apoptosis, were observed in the HHcy group compared with the control group; these effects were associated with increased expression of NOX2 and NOX4 and decreased nephrin expression in renal tissue from SHRs with HHcy. HHcy-induced changes were counteracted by LFA and HFA treatment. Apart from lower levels of NOX2 in the HHcy + HFA group, there were no significant differences in other indicators between the HHcy + LFA and HHcy + HFA groups. These results suggest that even at a low dose, FA can reduce plasma Hcy and attenuate HHcy-induced glomerular injury by inhibiting oxidative stress and apoptosis.

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Acknowledgements

This study was supported by the Shandong Provincial Key Research and Development Programme Foundation, China (Grant No. 2018GSF118009), the Technology Programme Foundation of Jinan, China (Grant No. 201821007), and the Shandong Provincial Medical Science and Technology Development Programme Foundation, China (Grant No. 2017WS462).

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  1. These authors contributed equally: Ning Gao, Yuzhen Zhang

Authors and Affiliations

  1. Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China

    Ning Gao, Ping Cao, Xuan Zhao & Rui Xu

  2. Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China

    Yuzhen Zhang

  3. Department of Cardiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China

    Lei Lei, Lin Lin & Rui Xu

  4. Department of Clinical Nutrition, The People’s Hospital of Zhangqiu, Jinan, Shandong, China

    Li Li

  5. Department of Geriatric Medicine, Tai’an City Central Hospital, Tai’an, Shandong, China

    Ping Cao

  6. Department of Cardiovascular Medicine, People’s Hospital of Dongying, Dongying, Shandong, China

    Xuan Zhao

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Contributions

NG and RX designed the experiment; NG, YZZ, LLi, PC, and LLin performed the experiments; LLei, and XZ analyzed the data and prepared the figures; NG, YZZ, and RX wrote the manuscript; and RX had primary responsibility for the final content. All authors read and approved the final manuscript.

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Correspondence to Rui Xu.

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Gao, N., Zhang, Y., Lei, L. et al. Low doses of folic acid can reduce hyperhomocysteinemia-induced glomerular injury in spontaneously hypertensive rats. Hypertens Res 43, 1182–1191 (2020). https://doi.org/10.1038/s41440-020-0471-8

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