PMID- 35806147
OWN - NLM
STAT- MEDLINE
DCOM- 20220712
LR  - 20220716
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 13
DP  - 2022 Jun 27
TI  - Blocking of SGLT2 to Eliminate NADPH-Induced Oxidative Stress in Lenses of 
      Animals with Fructose-Induced Diabetes Mellitus.
LID - 10.3390/ijms23137142 [doi]
LID - 7142
AB  - Chronic hyperglycemia triggers an abnormal rise in reactive oxygen species (ROS) 
      that leads to blindness in patients with diabetes mellitus (DM) and cataracts. In 
      this study, the effects of dapagliflozin, metformin and resveratrol on ROS 
      production were investigated in lens epithelial cells (LECs) of animals with 
      fructose-induced DM. LECs were isolated from patients without DM, or with DM 
      devoid of diabetic retinopathy. Animals were treated with 10% fructose for 8 
      weeks to induce DM, which was verified by monitoring blood pressure and serum 
      parameters. For drug treatments, 1.2 mg/day of dapagliflozin was given for 2 
      weeks, 500 mg/kg/day of metformin was given, and 10 mg/kg/day of resveratrol was 
      given. Dihydroethidium was used to stain endogenous O(2) (-) production in vivo 
      of the LECs. Superoxide production was expressed in the cataract of DM, or 
      patients without DM. Sodium-glucose cotransporter 2 (SGLT2), glucose transporter 
      1 (GLUT1), GLUT5, the reduced form of nicotinamide adenine dinucleotide phosphate 
      (NADPH) oxidase subunit p47/p67-phox, NOX4 and RAGE were significantly increased 
      in LECs with DM. In addition, the dapagliflozin treatment reduced GLUT5, 
      p47/p67-phox, NADPH oxidase 4 (NOX4) and receptor for advanced glycation end 
      products (RAGE) expressions. On the contrary, metformin or resveratrol inhibited 
      p47-phox, GLUT5, and SGLT2 expressions, but not nuclear factor erythroid 
      2-related factor 2 (NRF2). In summary, dapagliflozin, metformin or resveratrol 
      down-regulated p47-phox expression through SGLT2 inactivation and ROS reduction. 
      These important findings imply that SGLT2 can be blocked to ameliorate oxidative 
      stress in the cataracts of DM patients.
FAU - Chen, Ying-Ying
AU  - Chen YY
AD  - Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 
      81362, Taiwan.
AD  - School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
FAU - Wu, Tsung-Tien
AU  - Wu TT
AD  - Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 
      81362, Taiwan.
AD  - School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
FAU - Ho, Chiu-Yi
AU  - Ho CY
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 81362, Taiwan.
AD  - Department of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 
      80424, Taiwan.
FAU - Yeh, Tung-Chen
AU  - Yeh TC
AD  - Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans 
      General Hospital, Kaohsiung 81362, Taiwan.
FAU - Sun, Gwo-Ching
AU  - Sun GC
AUID- ORCID: 0000-0001-7626-8896
AD  - Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung 
      81362, Taiwan.
FAU - Tseng, Ching-Jiunn
AU  - Tseng CJ
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 81362, Taiwan.
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung 40402, Taiwan.
FAU - Cheng, Pei-Wen
AU  - Cheng PW
AUID- ORCID: 0000-0002-5997-9247
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 81362, Taiwan.
AD  - Department of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 
      80424, Taiwan.
LA  - eng
GR  - KSVGH110-141/Kaohsiung Veterans General Hospital/
PT  - Journal Article
DEP - 20220627
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Sodium-Glucose Transporter 2)
RN  - 30237-26-4 (Fructose)
RN  - 53-59-8 (NADP)
RN  - 9100L32L2N (Metformin)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - *Cataract
MH  - *Diabetes Mellitus
MH  - Fructose/adverse effects
MH  - *Metformin/pharmacology
MH  - NADP/metabolism
MH  - NADPH Oxidases/metabolism
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor for Advanced Glycation End Products/metabolism
MH  - Resveratrol/pharmacology
MH  - Sodium-Glucose Transporter 2/metabolism
PMC - PMC9266761
OTO - NOTNLM
OT  - NADPH oxidase
OT  - cataract
OT  - glucose transporter
OT  - resveratrol
OT  - type 2 diabetes mellitus
COIS- The authors of this study declare no competing interest.
EDAT- 2022/07/10 06:00
MHDA- 2022/07/14 06:00
PMCR- 2022/06/27
CRDT- 2022/07/09 01:11
PHST- 2022/05/25 00:00 [received]
PHST- 2022/06/20 00:00 [revised]
PHST- 2022/06/24 00:00 [accepted]
PHST- 2022/07/09 01:11 [entrez]
PHST- 2022/07/10 06:00 [pubmed]
PHST- 2022/07/14 06:00 [medline]
PHST- 2022/06/27 00:00 [pmc-release]
AID - ijms23137142 [pii]
AID - ijms-23-07142 [pii]
AID - 10.3390/ijms23137142 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Jun 27;23(13):7142. doi: 10.3390/ijms23137142.