Mitochondrial dysfunction related to cell damage induced by 3-hydroxykynurenine and 3-hydroxyanthranilic acid: Non-dependent-effect of early reactive oxygen species production

Ocampo, Jazmin Reyes; Ramírez-Ortega, Daniela; Cervantes, Gustavo Ignacio Vázquez; Pineda, Benjamín; Balderas, Pavel Montes de Oca; González-Esquivel, Dinora F.; Sánchez-Chapul, Laura; Lugo-Huitrón, Rafael; Silva-Adaya, Daniela; Rı́os, Camilo; Jiménez-Anguiano, Anabel; Cruz, Verónica Pérez-De La

doi:10.1016/j.neuro.2015.08.003

Cited by 53 publications

(60 citation statements)

References 51 publications

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“…It is important to mention that the basal extracellular concentrations of 3-OH-L-KYN in the rat brain (2 nM) are far below the above mentioned levels [224]. A recent study assessing the effects of 3-OH-L-KYN and 3-OH-ANA with regard to mitochondrial dysfunction demonstrated that both compounds decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction in a concentration-dependent manner in association with an impairment of mitochondrial membrane potential [225]. However, these findings were not related to alterations in ROS production or lipid peroxidation, probably due to the demonstrated hydroxyl radical and peroxynitrite scavenging activities of both compounds [225].…”

Section: -Hydroxy-l-kynurenine and 3-hydroxyanthranilic Acidmentioning

confidence: 97%

“…A recent study assessing the effects of 3-OH-L-KYN and 3-OH-ANA with regard to mitochondrial dysfunction demonstrated that both compounds decreased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction in a concentration-dependent manner in association with an impairment of mitochondrial membrane potential [225]. However, these findings were not related to alterations in ROS production or lipid peroxidation, probably due to the demonstrated hydroxyl radical and peroxynitrite scavenging activities of both compounds [225]. Summarily, the concentrationand time-dependent toxic effects of 3-OH-L-KYN and 3-OH-ANA include the impairment of cellular energy metabolism, but the accompanying role of early ROS production is controversial.…”

Section: -Hydroxy-l-kynurenine and 3-hydroxyanthranilic Acidmentioning

confidence: 99%

See 1 more Smart Citation

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Zádori

Veres

Szalárdy

et al. 2018

JAD

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The pathomechanism of Alzheimer's disease (AD) certainly involves mitochondrial disturbances, glutamate excitotoxicity, and neuroinflammation. The three main aspects of mitochondrial dysfunction in AD, i.e., the defects in dynamics, altered bioenergetics, and the deficient transport act synergistically. In addition, glutamatergic neurotransmission is affected in several ways. The balance between synaptic and extrasynaptic glutamatergic transmission is shifted toward the extrasynaptic site contributing to glutamate excitotoxicity, a phenomenon augmented by increased glutamate release and decreased glutamate uptake. quinolinic acid, has been demonstrated to be neurotoxic, promoting glutamate excitotoxicity, reactive oxygen species production, lipid peroxidation, and microglial neuroinflammation, and its abundant presence in AD pathologies has been demonstrated. Finally, the neuroprotective metabolite, kynurenic acid, has been associated with antagonistic effects at glutamate receptors, free radical scavenging, and immunomodulation, giving rise to potential therapeutic implications. This review presents the multiple connections of KYN pathwayrelated alterations to three main domains of AD pathomechanism, such as mitochondrial dysfunction, excitotoxicity, and neuroinflammation, implicating possible therapeutic options.3

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Section: -Hydroxy-l-kynurenine and 3-hydroxyanthranilic Acidmentioning

confidence: 97%

Section: -Hydroxy-l-kynurenine and 3-hydroxyanthranilic Acidmentioning

confidence: 99%

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Zádori

Veres

Szalárdy

et al. 2018

JAD

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“…NO at high concentrations reacts rapidly in the peroxide microenvironment at the site of injury to produce peroxynitrite ion (ONOO-), directly or indirectly leading to the damage of target cells and tissues (9). Inflammatory reactions can markedly promote IRI (10).…”

Section: Introductionmentioning

confidence: 99%

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

et al. 2015

Molecular Medicine Reports

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Abstract. Honokiol is the predominant active ingredient in the commonly used traditional Chinese medicine, Magnolia, which has been confirmed in previous studies to exhibit anti-oxidation, antimicrobial, antitumor and other pharmacological effects. However, its effects on renal ischemia/reperfusion injury (IRI) remain to be elucidated. The present study aimed to examine the effects of honokiol on renal IRI, and to investigate its potential protective mechanisms in the heart. Male adult Wistar albino rats were induced into a renal IRI model. Subsequently, the levels of serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), and the levels of serum nitrite and the kidney nitrite were examined in the IRI group. The levels of oxidative stress, inducible nitric oxide synthase (iNOS), inflammatory factors and caspase-3 were evaluated using a series of commercially available kits. The levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the protein expression levels of STAT3 were determined using western blotting. Pretreatment with honokiol significantly reduced the levels of serum creatinine, BUN, ALT, AST and ALP, and the level of nitrite in the kidney of the IRI group, compared with the control group. The levels of malondialdehyde, the activity of myeloperoxidase, and the gene expression and activity of iNOS were reduced in the IRI rats, compared with the sham-operated rats, whereas the levels of superoxide dismutase and catalase were increased following treatment with honokiol in the IRI rats. In addition, the expression levels of tumor necrosis factor-α and interleukin-6 in the IRI rats were increased by honokiol. Treatment with honokiol suppressed the protein expression levels of p-STAT3 and caspase-3 in the IRI rats. These findings indicated that honokiol protects against renal IRI via the suppression of oxidative stress, iNOS, inflammation and STAT3 in the rat.

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“…This is possible because the measurement of both tests relies on different intracellular processes, the NR assay reflects the incorporation of NR dye into lysosomes of viable cells and the MTT assay determines the conversion of yellow MTT tetrazolium salt to a blue formazan by mitochondrial succinate dehydrogenase activity. Thus, the direct inhibitory influence of intermediate KYN pathway metabolites such as 3-hydroxykynurenine and 3-hydroxyanthranilic acid or final KYN metabolite NAD + on mitochondrial enzyme function independent of cell viability cannot be ruled out [31, 32]. …”

Section: Discussionmentioning

confidence: 99%

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

Matysik-Woźniak

Turski²,

Turska

et al. 2019

Ophthalmic Res

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Kynurenine (KYN) is a metabolite of tryptophan, proposed for the treatment of corneal diseases. Our goal was to evaluate the effects of KYN on normal human corneal and conjunctival epithelial cells in vitro and the re-epithelization of corneal erosion in rabbits. In our study, we used corneal (10.014 pRSV-T) and conjunctival (HC0597) epithelium cell cultures. KYN was applied at a concentration range of 1–100 µM for 24 and 48 h. We examined the effects on cellular metabolism, viability, interleukin-1β (IL-1β), IL-6, IL-10 secretion, cytoskeleton organization and transwell migration ability. Following a bilateral corneal de-epithelialization, the rabbits received drops containing 1% KYN and a saline solution to the contralateral control eye, 5 times daily. Digital images were analyzed using the EPCO 2000 software. The metabolic activity of cells was slightly decreased by KYN in the corneal but not in the conjunctival epithelium. The viability of both epithelia was improved by KYN; it caused alterations in the secretion of IL-6 and IL-10 but not IL-1β. It had no impact on both epithelia morphology and the organization of the cellular cytoskeleton. KYN stimulated the formation of pseudopodia projections in both epithelia in vitro, which may be important in terms of wound healing. However, there were no differences in the re-epithelization rate in vivo. At the tested concentrations, KYN was not toxic for the corneal and the conjunctival epithelium in vitro and did not affect corneal re-epithelization in rabbits in vivo. Our results suggest that KYN may be taken into consideration for the treatment of ocular disorders.

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Mitochondrial dysfunction related to cell damage induced by 3-hydroxykynurenine and 3-hydroxyanthranilic acid: Non-dependent-effect of early reactive oxygen species production

Cited by 53 publications

References 51 publications

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Alzheimer’s Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies

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