PMID- 32439914
OWN - NLM
STAT- MEDLINE
DCOM- 20211011
LR  - 20211011
IS  - 1348-4214 (Electronic)
IS  - 0916-9636 (Linking)
VI  - 43
IP  - 11
DP  - 2020 Nov
TI  - Low doses of folic acid can reduce hyperhomocysteinemia-induced glomerular injury 
      in spontaneously hypertensive rats.
PG  - 1182-1191
LID - 10.1038/s41440-020-0471-8 [doi]
AB  - 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.
FAU - Gao, Ning
AU  - Gao N
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan, Shandong, China.
FAU - Zhang, Yuzhen
AU  - Zhang Y
AD  - Department of Neurosurgery, The First Affiliated Hospital of Shandong First 
      Medical University, Jinan, Shandong, China.
FAU - Lei, Lei
AU  - Lei L
AD  - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan, Shandong, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Clinical Nutrition, The People's Hospital of Zhangqiu, Jinan, 
      Shandong, China.
FAU - Cao, Ping
AU  - Cao P
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan, Shandong, China.
AD  - Department of Geriatric Medicine, Tai'an City Central Hospital, Tai'an, Shandong, 
      China.
FAU - Zhao, Xuan
AU  - Zhao X
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan, Shandong, China.
AD  - Department of Cardiovascular Medicine, People's Hospital of Dongying, Dongying, 
      Shandong, China.
FAU - Lin, Lin
AU  - Lin L
AD  - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan, Shandong, China.
FAU - Xu, Rui
AU  - Xu R
AD  - Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jinan, Shandong, China. xuruicn@hotmail.com.
AD  - Department of Cardiology, The First Affiliated Hospital of Shandong First Medical 
      University, Jinan, Shandong, China. xuruicn@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200521
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Membrane Proteins)
RN  - 0 (nephrin)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 12001-76-2 (Vitamin B Complex)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.6.3.- (Cybb protein, rat)
RN  - EC 1.6.3.- (NADPH Oxidase 2)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (Nox4 protein, rat)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Drug Evaluation, Preclinical
MH  - Folic Acid/*administration & dosage
MH  - Homocysteine/metabolism
MH  - Hyperhomocysteinemia/*complications/drug therapy
MH  - Hypertension/complications
MH  - Kidney Cortex/*drug effects/enzymology
MH  - Kidney Diseases/blood/*etiology/pathology/prevention & control
MH  - Male
MH  - Malondialdehyde/blood
MH  - Membrane Proteins/metabolism
MH  - NADPH Oxidase 2/metabolism
MH  - NADPH Oxidase 4/metabolism
MH  - Podocytes/metabolism/ultrastructure
MH  - Random Allocation
MH  - Rats, Inbred SHR
MH  - Superoxide Dismutase/blood
MH  - Vitamin B Complex/*administration & dosage
OTO - NOTNLM
OT  - Folic acid
OT  - Glomerular injury
OT  - HHcy
OT  - Hypertension
OT  - NADPH oxidase
EDAT- 2020/05/23 06:00
MHDA- 2021/10/12 06:00
CRDT- 2020/05/23 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2020/04/22 00:00 [accepted]
PHST- 2020/04/10 00:00 [revised]
PHST- 2020/05/23 06:00 [pubmed]
PHST- 2021/10/12 06:00 [medline]
PHST- 2020/05/23 06:00 [entrez]
AID - 10.1038/s41440-020-0471-8 [pii]
AID - 10.1038/s41440-020-0471-8 [doi]
PST - ppublish
SO  - Hypertens Res. 2020 Nov;43(11):1182-1191. doi: 10.1038/s41440-020-0471-8. Epub 
      2020 May 21.