Effect of Nitric Oxide on<i>Acanthamoeba castellanii</i>

Yim, Bora; Park, Joo Hee; Jeong, Hyejoong; Hong, Jinkee; Kim, Martha; Chang, Minwook; Chuck, Roy S.; Park, Keun

doi:10.1167/iovs.18-23786

Cited by 6 publications

(5 citation statements)

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“… 13 – 15 Exogenous delivery of NO by adding NO donors, sodium nitrite (NaNO 2 ) and sodium nitroprusside (SNP), in planktonic cultures of A. castellanii demonstrated that killing Acanthamoeba was concentration dependent for both trophozoite and cyst forms. 11 However, we also found that the anti- Acanthamoeba effect and human corneal epithelial cell (HCEC) toxicity were proportional: NaNO 2 showed a weak anti- Acanthamoeba effect and less corneal epithelial toxicity, while SNP showed a strong anti- Acanthamoeba effect and severe HCEC toxicity. 11 …”

Section: Introductionmentioning

confidence: 85%

“… 11 However, we also found that the anti- Acanthamoeba effect and human corneal epithelial cell (HCEC) toxicity were proportional: NaNO 2 showed a weak anti- Acanthamoeba effect and less corneal epithelial toxicity, while SNP showed a strong anti- Acanthamoeba effect and severe HCEC toxicity. 11 …”

Section: Introductionmentioning

confidence: 85%

“…We previously reported the anti- Acanthamoeba effect of nitric oxide (NO). 11 NO is a radical gas and a key player in a common antibacterial mechanism in mammalian hosts. 12 NO synthesized by activated macrophages is a broad-spectrum bactericidal agent that can kill both gram-positive and gram-negative bacteria.…”

Section: Introductionmentioning

confidence: 99%

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Effects of In Vitro Combination of Nitric Oxide Donors and Hypochlorite on Acanthamoeba castellanii Viability

Park,

Park

2023

Trans. Vis. Sci. Tech.

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Purpose To investigate the combined anti- Acanthamoeba effects of nitric oxide (NO) donors and hypochlorite to maximize amoebicidal outcomes while minimizing damage to human corneal epithelial cells (HCECs). Methods Acanthamoeba castellanii and primary cultured HCECs and keratocytes were treated with sodium hypochlorite (NaOCl), NO donors (sodium nitroprusside [SNP] and sodium nitrite [NaNO 2 ]), or a combination of hypochlorite and NO donors. The viability of A. castellanii , HCECs, and keratocytes was assessed. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration of NaOCl and NO donors were determined. The activation of mammalian targets of rapamycin (mTOR) and ERK and the expression of nitrite reductase and Nrf2 were assessed in HCECs using Western blot analysis. The cysticidal effects of combined NaOCl and NO donors were also evaluated. Results A dose-dependent toxicity was observed in A. castellanii , HCECs, and keratocytes when treated with NaOCl and SNP. The range of tested NaNO 2 concentrations showed no significant toxicity to HCECs; however, dose-dependent toxicity to A. castellanii was observed. The MIC of NaOCl against HCECs and A. castellanii was 8.0 mg/mL. The MIC of NaNO 2 and SNP was 500 mM and 10 mM in both HCECs and A. castellanii , respectively . Weak attenuation of the mTOR and ERK phosphorylation was observed and Nrf2 expression decreased slightly after exposure of HCECs to 2.0 mg/mL NaOCl. For the combination treatment, NaOCl (0.125 mg/mL) was selected based on the safety of HCECs and the toxicity of A. castellanii. A more potent anti- Acanthamoeba effect and HCEC toxicity were observed when NaOCl was combined with SNP rather than NaNO 2 . Conclusions Combined NaOCl and NO donors had a stronger anti- Acanthamoeba effect compared to either drug alone. Translational Relevance This study demonstrates that the combined use of various drugs for the treatment of Acanthamoeba infection can enhance the anti- Acanthamoeba effect while minimizing the toxicity of the individual drug.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 85%

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Effects of In Vitro Combination of Nitric Oxide Donors and Hypochlorite on Acanthamoeba castellanii Viability

Park,

Park

2023

Trans. Vis. Sci. Tech.

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“…Acanthamoeba keratitis is among the most intractable of corneal infectious diseases leading to blindness ( 107 ). Recently, Yim et al ( 108 ) demonstrated the anti-Acanthamoeba effect using NO donors.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide: an old drug but with new horizons in ophthalmology—a narrative review

Lee,

Park

2023

Ann Transl Med

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Background and Objective Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed. Methods A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. Key Content and Findings NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate. Three types of NOS (eNOS, nNOS, and iNOS) are abundantly expressed in the eye under normal physiologic or pathologic conditions. The biological effect of NO in the eye is dose dependent. Low intraocular NO concentrations, produced by eNOS or nNOS, have various cellular effects, including vasodilation, intraocular pressure (IOP) regulation, and neuroprotection. iNOS induced under pathologic ocular conditions produces high NO concentrations in the local environment and mediates tissue inflammation, ocular cell apoptosis, and neurodegeneration. In particular, increased iNOS has been reported in glaucoma and retinal ischemic or degenerative diseases. NO plays a vital role in ocular injury. NO can facilitate ocular surface wound healing while eradicating pathogens such as bacteria and Acanthamoeba in chemical burns or infectious keratitis. Furthermore, NO has antifibrotic activity via the cyclic guanosine monophosphate (cGMP) signaling pathway. NO causes smooth muscle relaxation, which can be used to inhibit myopia progression in children. NO can be a stem cell modulator and may help in treating ocular stem cell disorders. Conclusions Because of its diverse biologic effects, NO can be a key player in regulating ocular inflammation in various ocular diseases, aiding ocular surface wound healing, controlling IOP in glaucoma, alleviating retinal disease, and suppressing myopia progression. Although there remain limitations to the effective use of highly unstable state, gaseous NO, the role of NO in the field of ophthalmology can be greatly expanded through the development of novel NO donors and effective delivery platforms.

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“…Nitric oxide coated with SiNPs showed toxicity on corneal epithelial cells at 100 µg/mL. (Yim et al, 2018) Nanoemulsions Coumarin rich Pterocaulon balansae (methanol extract)…”

Section: A Castellaniimentioning

confidence: 99%

Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba

et al. 2020

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Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major endproduct in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time.

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Effect of Nitric Oxide onAcanthamoeba castellanii

Abstract: Our results demonstrated the anti-Acanthamoeba effect of exogenous NO. This finding suggests that NO-releasing drug platforms, including nano-carriers, can be a promising therapeutic strategy for Acanthamoeba keratitis.

Cited by 6 publications

References 50 publications

Effects of In Vitro Combination of Nitric Oxide Donors and Hypochlorite on Acanthamoeba castellanii Viability

Effects of In Vitro Combination of Nitric Oxide Donors and Hypochlorite on Acanthamoeba castellanii Viability

Nitric oxide: an old drug but with new horizons in ophthalmology—a narrative review

Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba

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