PMID- 35504734
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230504
IS  - 2168-8370 (Electronic)
IS  - 2168-8362 (Print)
IS  - 2168-8362 (Linking)
VI  - 11
IP  - 1
DP  - 2023 Jan 2
TI  - The therapeutic prospect of zinc oxide nanoparticles in experimentally induced 
      diabetic nephropathy.
PG  - 2069966
LID - 10.1080/21688370.2022.2069966 [doi]
LID - 2069966
AB  - Diabetic nephropathy (DN) is the most frequent cause of end-stage renal failure. 
      Zinc oxide nanoparticles (ZnO-NPs) are promising antidiabetic agents. Our aim was 
      to evaluate the prospective efficacy of ZnO-NPs in treating DN in 
      streptozotocin-induced diabetic rats. Rats were randomly dispersed into three 
      sets: control group, DN group and DN + ZnO-NPs group. ZnO-NPs were given at a 
      dose of 10 mg/kg/day by oral gavage for 4 weeks. Urine and blood samples were 
      processed for biochemical analyses. Kidney samples were managed for light and 
      electron microscopy studies. Immune histochemical staining of P53, aquaporin11 
      (AQP11) and mechanistic target of rapamycin (mTOR) were performed. Gene analyses 
      of nephrin, podocin, beclin-1, LC3 and p62 were done. Administration of ZnO-NPs 
      ameliorated the functional and histopathological alterations of the kidney in a 
      rat model of diabetic nephropathy. ZnO-NPs retained the constancy of the 
      glomerular filtration barrier and restored almost normal renal structure. This 
      was confirmed by upregulation of mRNA expression of podocyte markers (nephrin and 
      podocin) and AQP11 immune histochemical expression in the renal tubules. The 
      beneficial outcomes of ZnO-NPs might be attributed to activation of autophagy 
      through inhibiting mTOR signaling pathway. ZnO-NPs enhanced beclin-1 and LC3 mRNA 
      expressions and reduced p62 mRNA expression. ZnO-NPs also exerted anti-apoptotic 
      potential (evidenced by the decrease in p53 immune expression), anti-inflammatory 
      and anti-oxidant effect [endorsed by suppression of serum cyclooxygenase-2 
      (COX-2) enzyme activity, tissue nuclear factor kappa beta (NF-kappaB) level and blood 
      hypoxia-inducible factors (HIF-1alpha) level]. These results may point the way to an 
      effective therapy of DN.Abbreviations: AQP11 Aquaporin11; BUN: Blood urea 
      nitrogen; COX-2: Cyclooxygenase-2; DAB: 3, 3'-diaminobenzidine; DM: Diabetes 
      mellitus; DN: Diabetic nephropathy; ELISA: Enzyme-linked immunosorbent assay; 
      H&E: Hematoxylin & eosin; HIF-1alpha: Hypoxia-inducible factors; iNOS: inducible 
      nitric oxide synthase; LC3: Microtubule-associated protein 1 light chain 3; mTOR: 
      Mechanistic target of rapamycin; NF-kappaB: Nuclear factor kappa beta; NPs: 
      Nanoparticles; PAS: Periodic acid Schiff; PCR: Polymerase chain reaction; PGE2: 
      Prostaglandin E2; ROS: Reactive oxygen species; STZ: Streptozotocin; X +/- SEM: 
      Mean +/- standard error of means; Zn: Zinc; ZnO-NPs: Zinc oxide nanoparticles.
FAU - Abd El-Baset, Samia A
AU  - Abd El-Baset SA
AUID- ORCID: 0000-0003-4147-3632
AD  - Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig 
      University, Zagazig Egypt.
FAU - Mazen, Nehad F
AU  - Mazen NF
AUID- ORCID: 0000-0002-2942-2763
AD  - Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig 
      University, Zagazig Egypt.
FAU - Abdul-Maksoud, Rehab S
AU  - Abdul-Maksoud RS
AUID- ORCID: 0000-0002-2241-1586
AD  - Department of Medical Biochemistry, Faculty of Medicine, Zagazig University, 
      Zagazig Egypt.
FAU - Kattaia, Asmaa A A
AU  - Kattaia AAA
AUID- ORCID: 0000-0002-7188-0100
AD  - Department of Medical Histology and Cell Biology, Faculty of Medicine, Zagazig 
      University, Zagazig Egypt.
LA  - eng
PT  - Journal Article
DEP - 20220503
PL  - United States
TA  - Tissue Barriers
JT  - Tissue barriers
JID - 101601065
RN  - SOI2LOH54Z (Zinc Oxide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - 0 (NF-kappa B)
RN  - 5W494URQ81 (Streptozocin)
RN  - 0 (Beclin-1)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Diabetic Nephropathies/drug therapy
MH  - *Zinc Oxide/pharmacology/therapeutic use/metabolism
MH  - Cyclooxygenase 2/metabolism/therapeutic use
MH  - NF-kappa B/metabolism
MH  - Streptozocin/pharmacology/therapeutic use
MH  - *Diabetes Mellitus, Experimental/drug therapy/metabolism
MH  - Beclin-1/metabolism
MH  - Prospective Studies
MH  - Tumor Suppressor Protein p53
MH  - TOR Serine-Threonine Kinases/metabolism/therapeutic use
MH  - *Nanoparticles
MH  - Sirolimus/therapeutic use
MH  - Hypoxia
MH  - RNA, Messenger/therapeutic use
PMC - PMC9870014
OTO - NOTNLM
OT  - Autophagy
OT  - diabetic nephropathy
OT  - mTOR
OT  - rats
OT  - zinc oxide nanoparticles
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/05/04 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/05/03
CRDT- 2022/05/03 21:52
PHST- 2022/05/04 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2022/05/03 21:52 [entrez]
PHST- 2023/05/03 00:00 [pmc-release]
AID - 2069966 [pii]
AID - 10.1080/21688370.2022.2069966 [doi]
PST - ppublish
SO  - Tissue Barriers. 2023 Jan 2;11(1):2069966. doi: 10.1080/21688370.2022.2069966. 
      Epub 2022 May 3.