Alpha-lipoic acid restores tear production in an animal model of dry eye

Andrade, Alexey S.; Salomon, Tiago Boeira; Behling, Camile S.; Mahl, Camila D.; Hackenhaar, Fernanda Schäfer; Putti, Jordana Salete; Benfato, Mara da Silveira

doi:10.1016/j.exer.2013.12.014

Cited by 43 publications

(33 citation statements)

References 37 publications

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“…[40][41][42] The levels of HNE in tear and conjunctiva were observed to be significantly higher in Sjögren syndrome (SS) compared with healthy controls. 43,44 In the present study, L-carnitine was found to significantly suppress the ROS production as Oxidative biomarker for DNA damage. (A) Representative images showed 8-OHdG immunohistochemical staining in primary HCECs exposed to hyperosmotic media without or with L-carnitine.…”

Section: L-carnitine Protected Hcecs Against Overproduced Ros and Celmentioning

confidence: 50%

Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Hua

Deng

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Section: L-carnitine Protected Hcecs Against Overproduced Ros and Celmentioning

confidence: 50%

Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Hua

Deng

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Alpha‐lipoic acid (ALP) is an endogenously synthesized cofactor for mitochondrial enzyme complexes, and its biological effects include sequestration of ROS, interaction and regeneration of other antioxidants such as vitamin C and vitamin E and regulation of redox processes (Andrade et al. ).…”

Section: Preclinical Intervention Studiesmentioning

confidence: 99%

“…In a rat model of postmenopausal dry eye, ALP restored lacrimal function and improvements in the Schirmer test were noted in the treatment group. Alpha-lipoic acid (ALP) is an endogenously synthesized cofactor for mitochondrial enzyme complexes, and its biological effects include sequestration of ROS, interaction and regeneration of other antioxidants such as vitamin C and vitamin E and regulation of redox processes (Andrade et al 2014).…”

Section: Preclinical Intervention Studiesmentioning

confidence: 99%

Dry eye disease and oxidative stress

Seen

Tong

2017

Acta Ophthalmologica

207

149

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Dry eye, an age-related condition, is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability. Environmental factors are also often implicated in dry eye including exposure to pollutants, ultraviolet (UV) radiation and ozone as well as the chronic use of preserved eyedrops such as in the treatment of glaucoma. These factors increase oxidative stress and ocular surface inflammation. Here, we reviewed the cellular, animal and clinical studies that point to the role of oxidative stress in dry eye disease. The biomarkers used to indicate oxidative damage in ocular surface tissues include 8-hydroxy-2 deoxyguanosine (8-OHdG), 4-hydroxynonenal (HNE) and malondialdehyde (MDD). Antioxidative defences in the ocular surface occur in the form of tear proteins such as lactoferrin and S100A proteins, and enzymes such as superoxide dismutase (SOD), peroxidase, catalase and mitochondrial oxidative enzymes. An imbalance between the level of reactive oxygen species (ROS) and the action of protective enzymes will lead to oxidative damage, and possibly inflammation. A small number of interventional studies suggest that oxidative stress may be directly targeted in topical therapy of dry eye treatment. For example, in vitro studies suggest that L-carnitine and pterostilbene, a blueberry component may reduce oxidative stress, and in animal studies, alpha-lipoic acid (ALP) and selenoprotein P may be helpful. Examples of treatments used in clinical trials include vitamin B12 eyedrops and iodide iontophoresis. With recent emphasis on ageing medicine and preventive holistic health, as well as the role of environmental science, research on oxidative stress in the ocular surface is likely to have increasing impact in the coming years.

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“…Although BAC provides excellent antimicrobial properties in ophthalmic preparations, a large number of clinical and experimental investigations using in vitro or animal models suggested cytotoxic effects of even low BAC concentrations on several components of the eye (see [18]). The topical administration of BAC-containing eye drops may cause a variety of ocular surface changes, from ocular discomfort, redness, dryness, and tear film instability [19][20][21][22][23][24][25][26] to allergic, immune, inflammatory reactions [27][28][29], ocular irritation, scarring of the ocular surface with irreversible vision impairment [21,30,31], disruption of the blood-aqueous barrier inducing cystoid macular edema following cataract surgery [32,33], loss of goblet cells (see [27,34]) and, at higher concentrations, to the disruption of the corneal epithelium, induction of apoptosis or necrosis of Chang's conjunctival cells [31-33, 35, 36]. The proapoptotic effects were seen at very low concentrations of BAC with a threshold of toxicity found at about 0.005% (i.e., below the usual concentration used in most eye drops).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

Рогов

Goleva

Sukhanova

et al. 2020

Oxidative Medicine and Cellular Longevity

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Benzalkonium chloride (BAC) is currently the most commonly used antimicrobial preservative in ophthalmic solutions, nasal sprays, and cosmetics. However, a large number of clinical and experimental investigations showed that the topical administration of BAC-containing eye drops could cause a variety of ocular surface changes, from ocular discomfort to potential risk for future glaucoma surgery. BAC-containing albuterol may increase the risk of albuterol-related systemic adverse effects. BAC, commonly present in personal care products, in cosmetic products can induce irritation and dose-dependent changes in the cell morphology. The cationic nature of BAC (it is a quaternary ammonium) suggests that one of the major targets of BAC in the cell may be mitochondria, the only intracellular compartment charged negatively. However, the influence of BAC on mitochondria has not been clearly understood. Here, the effects of BAC on energy parameters of rat liver mitochondria as well as on yeast cells were examined. BAC, being a "weaker" uncoupler, potently inhibited respiration in state 3, diminished the mitochondrial membrane potential, caused opening of the Ca2+/Pi-dependent pore, blocked ATP synthesis, and promoted H 2 O 2 production by mitochondria. BAC triggered oxidative stress and mitochondrial fragmentation in yeast cells. BAC-induced oxidative stress in mitochondria and yeast cells was almost totally prevented by the mitochondria-targeted antioxidant SkQ1; the protective effect of SkQ1 on mitochondrial fragmentation was only partial. Collectively, these data showed that BAC acts adversely on cell bioenergetics (especially on ATP synthesis) and mitochondrial dynamics and that its prooxidant effect can be partially prevented by the mitochondria-targeted antioxidant SkQ1.

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Alpha-lipoic acid restores tear production in an animal model of dry eye

Cited by 43 publications

References 37 publications

Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Protective Effects of L-Carnitine Against Oxidative Injury by Hyperosmolarity in Human Corneal Epithelial Cells

Dry eye disease and oxidative stress

Mitochondrial Dysfunctions May Be One of the Major Causative Factors Underlying Detrimental Effects of Benzalkonium Chloride

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