Effect of General Anesthesia Duration on Recovery of Secretion and Biochemical Properties of Tear Fluid in the Post-Anesthetic Period

Zernii, Evgeni Yu; Baksheev, V. E.; Kabanova, E. I.; Tiulina, Veronika V.; Golovastova, Marina O.; Gancharova, Olga; Savchenko, M. A.; Sotikova, L. F.; Zamyatnin, Andrey A.; Filippov, P. P.; Senin, Ivan I.

doi:10.1007/s10517-018-4145-3

Cited by 9 publications

(15 citation statements)

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“…We speculate that in intact retinas the intrinsic antioxidant components were engaged in scavenging ROS and the remainder was insufficient to noticeably inhibit luminol oxidation in the assay. In any case, our data indicate that AOA of healthy retina is considerably lower than in the other ocular tissues measured by the same method [34,38,39]. Meanwhile, the high-intensity light illumination clearly enhances AOA.…”

Section: Discussionmentioning

confidence: 51%

“…Total antioxidant activity of retinal extracts was analyzed by means of hemoglobin/H 2 O 2 /luminol assay according to the standard procedure [37] with modifications described previously [34,38,39]. Briefly, 1–8 μM Trolox or retinal extract (4 mg/mL of total protein) was added to the reaction mixture, containing 0.01 mM luminol and 0.5 mM hemoglobin in PBS.…”

Section: Methodsmentioning

confidence: 99%

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Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant

et al. 2018

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Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD. Here, we examine oxidative processes induced in rabbit retina by excessive light illumination with or without premedication using mitochondria-targeted antioxidant SkQ1 (10-(6’-plastoquinonyl)decyltriphenyl-phosphonium). The retinal extracts obtained from animals euthanized within 1–7 days post exposure were analyzed for H2O2, malondialdehyde (MDA), total antioxidant activity (AOA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) using colorimetric and luminescence assays. Oxidation of visual arrestin was monitored by immunoblotting. The light exposure induced lipid peroxidation and H2O2 accumulation in the retinal cells. Unexpectedly, it prominently upregulated AOA in retinal extracts although SOD and GPx activities were compromised. These alterations were accompanied by accumulation of disulfide dimers of arrestin revealing oxidative stress in the photoreceptors. Premedication of the eyes with SkQ1 accelerated normalization of H2O2 levels and redox-status of lipids and proteins, contemporarily enhancing AOA and, likely, sustaining normal activity of GPx. Thus, SkQ1 protects the retina from light-induced oxidative stress and could be employed to suppress oxidative damage of proteins and lipids contributing to AMD.

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Section: Discussionmentioning

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant

et al. 2018

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“…These species are well suited for ophthalmological research due to many similarities in biomechanical properties of rabbit and human eyes [34]. Indeed, in our previous works rabbits were successfully employed for monitoring anesthesia-induced damage and oxidative stress in cornea on clinical, histological and biochemical levels [24, 27, 28].…”

Section: Discussionmentioning

confidence: 99%

Mitochondria-targeted antioxidant SKQ1 protects cornea from oxidative damage induced by ultraviolet irradiation and mechanical injury

et al. 2018

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BackgroundCornea protects the eye against natural and anthropogenic ultraviolet (UV) damage and mechanical injury. Corneal incisions produced by UV lasers in ophthalmic surgeries are often complicated by oxidative stress and inflammation, which delay wound healing and result in vision deterioration. This study trialed a novel approach to prevention and treatment of iatrogenic corneal injuries using SkQ1, a mitochondria-targeted antioxidant approved for therapy of polyethiological dry eye disease.MethodsRabbit models of UV-induced and mechanical corneal damage were employed. The animals were premedicated or treated with conjunctival instillations of 7.5 μM SkQ1. Corneal damage was assessed by fluorescein staining and histological analysis. Oxidative stress in cornea was monitored by measuring malondialdehyde (MDA) using thiobarbituric acid assay. Total antioxidant activity (AOA) was determined using hemoglobin/H2O2/luminol assay. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured using colorimetric assays.ResultsIn both models corneas exhibited fluorescein-stained lesions, histologically manifesting as basal membrane denudation, apoptosis of keratocytes, and stromal edema, which were accompanied by oxidative stress as indicated by increase in lipid peroxidation and decline in AOA. The UV-induced lesions were more severe and long healing as corneal endothelium was involved and GPx and SOD were downregulated. The treatment inhibited loss of keratocytes and other cells, facilitated re-epithelialization and stromal remodeling, and reduced inflammatory infiltrations and edema thereby accelerating corneal healing approximately 2-fold. Meanwhile the premedication almost completely prevented development of UV-induced lesions. Both therapies reduced oxidative stress, but only premedication inhibited downregulation of the innate antioxidant activity of the cornea.ConclusionsSkQ1 efficiently prevents UV-induced corneal damage and enhances corneal wound healing after UV and mechanical impacts common to ocular surgery. Its therapeutic action can be attributed to suppression of mitochondrial oxidative stress, which in the first case embraces all corneal cells including epitheliocytes, while in the second case affects residual endothelial cells and stromal keratocytes actively working in wound healing. We suggest SkQ1 premedication to be used in ocular surgery for preventing iatrogenic complications in the cornea.

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“…The rabbits were divided into 17 groups, 6 animals in each group (Table 1), and treated as described in Section 3. DES was induced by introducing rabbits into prolonged general anesthesia as described in previous studies [6,30]. Particularly, the animals were placed in prone position in a restraining device and subjected to repeating intramuscular injection of anesthetic preparation containing 1:2 mixture of 50 mg/mL tiletamine/zolazepam and 20 mg/mL xylazine hydrochloride to achieve continuous narcotic sleep for 6 h. For the anti-inflammation therapy, the animals received conjunctival instillations of the eye drops, consisting of either 50% dimethyl sulfoxide (DMSO) in normal saline (0.90% w/v of NaCl), or the same solution containing 0.5 mg/mL (0.05% (w/v)) zileuton.…”

Section: Experimental Modelmentioning

confidence: 99%

“…Tear secretion in animals was measured without topical or general anesthesia according to the following procedure [6,30]. Schirmer's test tear strips were placed under the lower eyelid the restrained animal for 5 min, and the length of the moistened paper (in mm) was recorded.…”

Section: Schirmer's Testmentioning

confidence: 99%

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

et al. 2020

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Dry eye syndrome (DES) is characterized by decreased tear production and stability, leading to desiccating stress, inflammation and corneal damage. DES treatment may involve targeting the contributing inflammatory pathways mediated by polyunsaturated fatty acids and their derivatives, oxylipins. Here, using an animal model of general anesthesia-induced DES, we addressed these pathways by characterizing inflammatory changes in tear lipidome, in correlation with pathophysiological and biochemical signs of the disease. The decline in tear production was associated with the infiltration of inflammatory cells in the corneal stroma, which manifested one to three days after anesthesia, accompanied by changes in tear antioxidants and cytokines, resulting in persistent damage to the corneal epithelium. The inflammatory response manifested in the tear fluid as a short-term increase in linoleic and alpha-linolenic acid-derived oxylipins, followed by elevation in arachidonic acid and its derivatives, leukotriene B4 (5-lipoxigenase product), 12-hydroxyeicosatetraenoic acid (12-lipoxigeanse product) and prostaglandins, D2, E2 and F2α (cyclooxygenase products) that was observed for up to 7 days. Given these data, DES was treated by a novel ophthalmic formulation containing a dimethyl sulfoxide-based solution of zileuton, an inhibitor of 5-lipoxigenase and arachidonic acid release. The therapy markedly improved the corneal state in DES by attenuating cytokine- and oxylipin-mediated inflammatory responses, without affecting tear production rates. Interestingly, the high efficacy of the proposed therapy resulted from the synergetic action of its components, namely, the general healing activity of dimethyl sulfoxide, suppressing prostaglandins and the more specific effect of zileuton, downregulating leukotriene B4 (inhibition of T-cell recruitment), as well as upregulating docosahexaenoic acid (activation of resolution pathways).

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Effect of General Anesthesia Duration on Recovery of Secretion and Biochemical Properties of Tear Fluid in the Post-Anesthetic Period

Cited by 9 publications

References 10 publications

Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant

Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant

Mitochondria-targeted antioxidant SKQ1 protects cornea from oxidative damage induced by ultraviolet irradiation and mechanical injury

Inflammation in Dry Eye Syndrome: Identification and Targeting of Oxylipin-Mediated Mechanisms

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