Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Hiroyoshi Kawada is active.

Publication


Featured researches published by Hiroyoshi Kawada.


PLOS ONE | 2011

Orally Active Multi-Functional Antioxidants Are Neuroprotective in a Rat Model of Light-Induced Retinal Damage

James Randazzo; Zifeng Zhang; Michael Hoff; Hiroyoshi Kawada; Andrew J. Sachs; Yang Yuan; Neena B. Haider; Peter F. Kador

Background Progression of age-related macular degeneration has been linked to iron dysregulation and oxidative stress that induce apoptosis of neural retinal cells. Since both antioxidants and chelating agents have been reported to reduce the progression of retinal lesions associated with AMD in experimental animals, the present study evaluates the ability of multi-functional antioxidants containing functional groups that can independently chelate redox metals and quench free radicals to protect the retina against light-induced retinal degeneration, a rat model of dry atrophic AMD. Methods/Results Proof of concept studies were conducted to evaluate the ability of 4-(5-hydroxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 4) and 4-(5-hydroxy-4,6-dimethoxypyrimidin-2-yl)-N,N-dimethyl-3,5-dioxopiperazine-1-sulfonamide (compound 8) to reduce retinal damage in 2-week dark adapted Wistar rats exposed to 1000 lx of light for 3 hours. Assessment of the oxidative stress markers 4- hydroxynonenal and nitrotyrosine modified proteins and Thioredoxin by ELISA and Western blots indicated that these compounds reduced the oxidative insult caused by light exposure. The beneficial antioxidant effects of these compounds in providing significant functional and structural protection were confirmed by electroretinography and quantitative histology of the retina. Conclusions/Significance The present study suggests that multi-functional compounds may be effective candidates for preventive therapy of AMD.


PLOS ONE | 2012

Novel Diabetic Mouse Models as Tools for Investigating Diabetic Retinopathy

Peter F. Kador; Peng Zhang; Jun Makita; Zifeng Zhang; Changmei Guo; James Randazzo; Hiroyoshi Kawada; Neena B. Haider; Karen Blessing

Objective Mouse models possessing green fluorescent protein (GFP) and/or human aldose reductase (hAR) in vascular tissues have been established and crossed with naturally diabetic Akita mice to produce new diabetic mouse models. Research Design and Methods Colonies of transgenic C57BL mice expressing GFP (SMAA-GFP), hAR (SMAA-hAR) or both (SMAA-GFP-hAR) in vascular tissues expressing smooth muscle actin were established and crossbred with C57BL/6-Ins2Akita/J (AK) mice to produce naturally diabetic offspring AK-SMAA-GFP and AK-SMAA-GFP-hAR. Aldose reductase inhibitor AL1576 (ARI) was administered in chow. Retinal and lenticular sorbitol levels were determined by HPLC. Retinal functions were evaluated by electroretinography (ERGs). Growth factor and signaling changes were determined by Western Blots using commercially available antibodies. Retinal vasculatures were isolated from the neural retina by enzymatic digestion. Flat mounts were stained with PAS-hematoxylin and analyzed. Results Akita transgenics developed DM by 8 weeks of age with blood glucose levels higher in males than females. Sorbitol levels were higher in neural retinas of AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice also had higher VEGF levels and reduced ERG scotopic b-wave function, both of which were normalized by AL1576. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors bFGF, IGF-1, and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK and P-44/42 MAPK that were also reduced by ARI treatment. Quantitative analysis of flat mounts in 18 week AK-SMAA-GFP-hAR mice revealed increased loss of nuclei/capillary length and a significant increase in the percentage of acellular capillaries present which was not seen in AK-SMAA-GFP-hAR treated with ARI. Conclusions/Significance These new mouse models of early onset diabetes may be valuable tools for assessing both the role of hyperglycemia and AR in the development of retinal lesions associated with diabetic retinopathy.


Experimental Eye Research | 2014

Novel transgenic mouse models develop retinal changes associated with early diabetic retinopathy similar to those observed in rats with diabetes mellitus.

Changmei Guo; Zifeng Zhang; Peng Zhang; Jun Makita; Hiroyoshi Kawada; Karen Blessing; Peter F. Kador

Retinal capillary pericyte degeneration has been linked to aldose reductase (AR) activity in diabetic retinopathy (DR). Since the development of DR in mice and rats has been reported to differ and that this may be linked to differences in retinal sorbitol levels, we have established new murine models of early onset diabetes mellitus as tools for investigating the role of AR in DR. Transgenic diabetic mouse models were developed by crossbreeding diabetic C57BL/6-Ins2(Akita)/J (AK) with transgenic C57BL mice expressing green fluorescent protein (GFP), human aldose reductase (hAR) or both in vascular tissues containing smooth muscle actin-α (SMAA). Changes in retinal sorbitol levels were determined by HPLC while changes of growth factors and signaling were investigated by Western Blots. Retinal vascular changes were quantitatively analyzed on elastase-digestion flat mounts. Results show that sorbitol levels were higher in neural retinas of diabetic AK-SMAA-GFP-hAR compared to AK-SMAA-GFP mice. AK-SMAA-GFP-hAR mice showed induction of the retinal growth factors VEGF, IGF-1, bFGF and TGFβ, as well as signaling changes in P-Akt, P-SAPK/JNK, and P-44/42 MAPK. Increased loss of nuclei per capillary length and a significant increase in the percentage of acellular capillaries presented in 18 week old AK-SMAA-GFP-hAR mice. These changes are similar to those observed in streptozotocin-induced diabetic rats. Retinal changes in both mice and rats were prevented by inhibition of AR. These studies confirm that the increased expression of AR in mice results in the development of retinal changes associated with the early stages of DR that are similar to those observed in rats.


Journal of Alzheimer's Disease | 2015

Effects of multifunctional antioxidants on mitochondrial dysfunction and amyloid-β metal dyshomeostasis.

Hiroyoshi Kawada; Karen Blessing; Tomomi Kiyota; Theodor Woolman; Lee C. Winchester; Peter F. Kador

BACKGROUND Redox-active metal dyshomeostasis and oxidative stress are associated with mitochondrial dysfunction and amyloid-β (Aβ) neurotoxicity that are linked to both the development of age-related macular degeneration (AMD) and Alzheimers disease (AD). As potential therapeutic agents, orally active multifunctional antioxidants (MFAOs) possessing two independent functional groups capable of binding redox-active metals and scavenging free radicals have been synthesized. OBJECTIVE To determine whether MFAOs affect mitochondrial function and reduce the presence of Aβ plaque formation. METHODS The MFAOs were evaluated in cultured SH-SY5Y cells and ARPE-19 cells. MFAO effects on mitochondrial function were investigated using rhodamine 123 staining after 2 hour exposure to MnCl2. MFAO effects on Aβ:Zn complex formation were evaluated with Zinquin staining and the ability of the Aβ:Zn complex to be degraded by matrix metalloproteinase-2 (MMP-2). The ability of MFAOs to reduce Aβ plaque in the brain was determined by orally feeding MFAO for one year to B6;129-Psen1tm1Mpm Tg(AβPPSwe,tauP301L) 1Lfa/Mmjax transgenic mice. Aβ levels were determined by ELISA. RESULTS MFAOs neither adversely affected mitochondrial signaling nor labile cytoplasmic zinc levels. MFAOs protected cells against Mn2+-induced mitochondrial dysfunction. MFAOs also removed zinc from the Aβ:Zn complex so that Aβ plaque could be degraded by MMP-2. Zinquin staining indicated that the removed zinc was present in the cytoplasm as labile zinc. Orally administered MFAOs reduced the brain levels of both Aβ40 and Aβ42 isoforms of Aβ. CONCLUSION These studies demonstrate that these MFAOs have metal attenuating properties with therapeutic potential in the treatment of both AMD and AD.


Journal of Medicinal Chemistry | 2015

Orally Bioavailable Metal Chelators and Radical Scavengers: Multifunctional Antioxidants for the Coadjutant Treatment of Neurodegenerative Diseases

Hiroyoshi Kawada; Peter F. Kador


Investigative Ophthalmology & Visual Science | 2012

Molecular Parameters Associated With Uptake Of Multi-functional Antioxidants For The Lens, Retina, And Brain

Hiroyoshi Kawada; Zifeng Zhang; Karen Blessing; Peter F. Kador


Investigative Ophthalmology & Visual Science | 2013

MULTIFUNCTIONAL ANTIOXIDANTS PROTECT CELLS FROM MITOCHONDRIAL DYSFUNCTION AND ABETA NEUROTOXICITY

Hiroyoshi Kawada; Peter F. Kador


Investigative Ophthalmology & Visual Science | 2013

TRANSGENIC AK-SMAA-GFP-HAR MICE SUPPORT THE PREMISE THAT ALDOSE REDUCTASE INITIATES DIABETIC RETINOPATHY

Changmei Guo; Peng Zhang; Zifeng Zhang; Hiroyoshi Kawada; Karen Blessing; Peter F. Kador


Investigative Ophthalmology & Visual Science | 2011

Comparative Studies Of High Hexose-induced Changes In Growth Factors And Mapk Signaling Of Rat Lenses In Vivo And In Vitro

Hiroyoshi Kawada; Zifeng Zhang; Peng Zhang; James Randazzo; Peter F. Kador


Investigative Ophthalmology & Visual Science | 2011

Orally Active Multi-functional Antioxidants Reduce Light-induced Retinal Damage In Rats

Peter F. Kador; J. Randazzo; Zifeng Zhang; Andrew Sachs; Yang Yuang; Hiroyoshi Kawada; Neena B. Haider

Collaboration


Dive into the Hiroyoshi Kawada's collaboration.

Top Co-Authors

Avatar

Peter F. Kador

University of Nebraska–Lincoln

View shared research outputs
Top Co-Authors

Avatar

Zifeng Zhang

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Karen Blessing

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Peng Zhang

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Changmei Guo

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

James Randazzo

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Neena B. Haider

University of Nebraska–Lincoln

View shared research outputs
Top Co-Authors

Avatar

Jun Makita

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Andrew J. Sachs

University of Nebraska Medical Center

View shared research outputs
Top Co-Authors

Avatar

Andrew Sachs

University of Nebraska–Lincoln

View shared research outputs
Researchain Logo
Decentralizing Knowledge