Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models

Hinkle, Louis; Le, Duong; Nguyên, Tam; Tran, Vy; Amankwa, Charles; Weston, Courtney; Shen, Haifa; Nguyen, Kytai T.; Rahimi, Maham; Acharya, Suchismita

doi:10.1016/j.nano.2021.102400

Cited by 4 publications

(3 citation statements)

References 39 publications

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“…In summary, SA-10 has previously been shown to reverse hyperinflammation and lung edema and significantly improve blood perfusion and physical endurance in acute and chronic ischemia models ( p < 0.05) [ 16 ]. Here we demonstrated that, SA-10 exerts antioxidant effects, immunomodulatory properties and functional preservation of the retina in the in vitro and in vivo ischemia/reperfusion retinal injury models.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the sulfone compound SA-10 was found to be a potent broad-spectrum (superoxides (O 2 − ) and hypoxyl radicals (HOCl)) ROS scavenger and NO donor [ 15 ]. In addition, SA-10 and a nano-encapsulated formulation of SA-10 showed significant protective effects on endothelial cells, and decreased inflammation and increased blood perfusion in a mouse hind limb ischemia model [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models

Amankwa,

Acha,

Dibas

et al. 2024

Cells

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Embolism, hyperglycemia, high intraocular pressure-induced increased reactive oxygen species (ROS) production, and microglial activation result in endothelial/retinal ganglion cell death. Here, we conducted in vitro and in vivo ischemia/reperfusion (I/R) efficacy studies of a hybrid antioxidant–nitric oxide donor small molecule, SA-10, to assess its therapeutic potential for ocular stroke. Methods: To induce I/R injury and inflammation, we subjected R28 and primary microglial cells to oxygen glucose deprivation (OGD) for 6 h in vitro or treated these cells with a cocktail of TNF-α, IL-1β and IFN-γ for 1 h, followed by the addition of SA-10 (10 µM). Inhibition of microglial activation, ROS scavenging, cytoprotective and anti-inflammatory activities were measured. In vivo I/R-injured mouse retinas were treated with either PBS or SA-10 (2%) intravitreally, and pattern electroretinogram (ERG), spectral-domain optical coherence tomography, flash ERG and retinal immunocytochemistry were performed. Results: SA-10 significantly inhibited microglial activation and inflammation in vitro. Compared to the control, the compound SA-10 significantly attenuated cell death in both microglia (43% vs. 13%) and R28 cells (52% vs. 17%), decreased ROS (38% vs. 68%) production in retinal microglia cells, preserved neural retinal function and increased SOD1 in mouse eyes. Conclusion: SA-10 is protective to retinal neurons by decreasing oxidative stress and inflammatory cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models

Amankwa,

Acha,

Dibas

et al. 2024

Cells

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“…In addition, 1% of SA-2 and 2% SA-9 encapsulated in poly lactic co-glycolic acid (PLGA) nanoparticle (NP) formulation was reported to exert sustained IOP-lowering effect with considerable bioavailability in the choroid, sclera, retina, and lens [82,84]. In a separate experiment, SA-10NP restored blood perfusion in a peripheral arterial disease (PAD) model of chronic ischemia using Balb/c mice [85]. As expected, SA-2 was also neuroprotective against endothelin-3, tertbutyl hydroperoxide (TBHP)-mediated insults and in trophic factor deprivation models of rat as well as human RGCs by reducing apoptosis and decreasing ROS levels (Table 1) [86].…”

Section: Synthetic Antioxidantsmentioning

confidence: 99%

Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future

Amankwa,

Kodati,

Donkor

et al. 2023

Biomedicines

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Reactive oxygen species play a significant role in the pathogenesis of various ocular neurodegenerative diseases especially glaucoma, age-related macular degeneration (AMD), and ocular ischemic stroke. Increased oxidative stress and the accumulation of ROS have been implicated in the progression of these diseases. As a result, there has been growing interest in exploring potential therapeutic and prophylactic strategies involving exogenous antioxidants. In recent years, there have been significant advancements in the development of synthetic therapeutic antioxidants for targeting reactive oxygen species (ROS) in neurodegenerative diseases. One area of focus has been the development of hybrid TEMPOL derivatives. In the context of ocular diseases, the application of next-generation hybrid TEMPOL antioxidants may offer new avenues for neuroprotection. By targeting ROS and reducing oxidative stress in the retina and optic nerve, these compounds have the potential to preserve retinal ganglion cells and trabecular meshwork and protect against optic nerve damage, mitigating irreversible blindness associated with these diseases. This review seeks to highlight the potential impact of hybrid TEMPOL antioxidants and their derivatives on ocular neurodegenerative disorders.

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Novel Small Molecules with Anti-Inflammatory and Anti-Angiogenic Activity in a Mouse Model of Oxygen-Induced Retinopathy

Dayoub,

Acharya,

Dibas

et al. 2024

Cells

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Retinopathy of prematurity (ROP) has a dual-phase disease pathology; in phase 1, hyperoxia-induced vaso-obliteration occurs in the retinal vasculature due to increased oxidative stress (OS) and inflammation, followed by phase 2, where hypoxia increases the overproduction of growth factors, inducing retinal neovascularization. Toll-like receptor 2 and -4 (TLR2 and TLR4) overactivation, hyper-inflammation, macrophages, and neutrophil infiltration contribute to the developing ROP. AVR-121 and AVR-123 are novel classes of small-molecule dual inhibitors of TLR2/4 tested in a human leukemia monocytic cell line (THP-1) and cord-blood-derived mononuclear cells (CBMCs). Both compounds inhibited TLR2/4 signaling-related inflammatory cytokines in THP-1 cells and inhibited VEGF-induced neovascularization in human retinal endothelial cells (HRECs), which are hallmarks of ROP. In an oxygen-induced retinopathy (OIR) murine model, the intraperitoneal injection of AVR-123 in the hyperoxia phase (P7–P12) or a nanosuspension eyedrop of AVR-123 in the hypoxic phase (P12–P17) significantly reduced vaso-obliteration, angiogenesis, and inflammatory cytokine profiles while not inhibiting the necessary growth factor VEGF in the juvenile mouse eyes. The results are consistent with our hypothesis that targeting the dual TLR2/4 pathway will reduce inflammation, angiogenesis, and vaso-obliteration in vitro and in vivo and reduce cytotoxic immune cells. AVR-123 has the potential to be developed as a therapy for ROP.

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Nano encapsulated novel compound SA-10 with therapeutic activity in both acute and chronic murine hindlimb ischemia models

Cited by 4 publications

References 39 publications

Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models

Neuroprotective and Anti-Inflammatory Activities of Hybrid Small-Molecule SA-10 in Ischemia/Reperfusion-Induced Retinal Neuronal Injury Models

Therapeutic Potential of Antioxidants and Hybrid TEMPOL Derivatives in Ocular Neurodegenerative Diseases: A Glimpse into the Future

Novel Small Molecules with Anti-Inflammatory and Anti-Angiogenic Activity in a Mouse Model of Oxygen-Induced Retinopathy

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