title: Alpha-lipoic acid restores tear production in an animal model of dry eye.
abstract: The tear film comprises a major mechanism for protection of the ocular surface against harmful external agents. Disruption of tear production can lead to dry eye syndrome, causing damage ranging from mild discomfort to scarring of the ocular surface with irreversible vision impairment. The production of tears by the lacrimal gland is influenced by neuroendocrine, hormonal, and immunological factors. Reactive oxygen and nitrogen species play an important role in its regulation. We assessed the effects of oxidative stress on antioxidant defenses in the lacrimal gland and ocular surface in ovariectomized rats supplemented with n-3 polyunsaturated fatty acids (n-3 PUFA) and alpha-lipoic acid (ALP). We found that n-3 PUFA did not measurably influence oxidative stress, but ALP had site-specific pro-oxidant and antioxidant effects, and was an important influence on ocular surface dry eye improvement. As an index of oxidative damage to proteins and lipids, we measured levels of carbonyl and malondialdehyde (MDA), respectively. Enzymatic antioxidant defenses were measured as total superoxide dismutase (tSOD) and glutathione peroxidase (GPx), and non-enzymatic defenses were estimated by vitamin C, total glutathione, and indirect oxide nitric levels. PUFA and ALP treatment restored lacrimal production with resulting improvement in the dry eye Schirmer test in all supplemented groups. The results indicated that reactive oxygen species resulting from oxidative stress in the lacrimal gland did not play an important role in dry eye through reactive oxygen species; however, alpha-lipoic acid altered the metabolism of reactive nitrogen species, causing increased activity of lacrimal peroxidase and improved lacrimal production.
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: alexey@fusion.med.br.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Andrade
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: tiago.salomon@hotmail.com.
authors.forename: Tiago B
authors.initials: TB
authors.lastname: Salomon
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: camilesaul@gmail.com.
authors.forename: Camile S
authors.initials: CS
authors.lastname: Behling
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: camila.mahl@gmail.com.
authors.forename: Camila D
authors.initials: CD
authors.lastname: Mahl
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: Fernanda.hackemhaar@hotmail.com.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Hackenhaar
authors.affiliation: Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: jojo.putti@gmail.com.
authors.forename: Jordana
authors.initials: J
authors.lastname: Putti
authors.affiliation: Graduate Program in Molecular and Cellular Biology, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Oxidative Stress Laboratory, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: mara.benfato@ufrgs.br.
authors.forename: Mara S
authors.initials: MS
authors.lastname: Benfato
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000378:metabolism; D003315:Cornea / Q000378:metabolism; D019587:Dietary Supplements; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000378:metabolism*; D019573:Epithelium, Corneal / Q000648:ultrastructure; D004958:Estradiol / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D013666:Tears / Q000378:metabolism*; D008063:Thioctic Acid / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D009566:Nitrates; D009573:Nitrites; D011374:Progesterone; D004958:Estradiol; D008315:Malondialdehyde; D008063:Thioctic Acid; D005978:Glutathione; D001205:Ascorbic Acid
keywords: Schirmer test; alpha-lipoic acid; dry eye; lacrimal peroxidase; n-3 PUFA; nitric oxide; oxidative stress