Hepatic oxidative stress in pigmented P23H rhodopsin transgenic rats with progressive retinal degeneration

被引:24
作者
Perdices, Lorena [1 ,2 ]
Fuentes-Broto, Lorena [1 ,3 ]
Segura, Francisco [1 ,4 ]
Ben Gdara, Neyla [5 ]
Isabel Sanchez-Cano, Ana [1 ,4 ,6 ]
Insa, Gema [1 ,4 ,6 ]
Orduna, Elvira [1 ,4 ,6 ]
Pinilla, Isabel [1 ,4 ,7 ]
机构
[1] Aragon Inst Hlth Res IIS Aragon, Ave San Juan Bosco 13, E-50009 Zaragoza, Spain
[2] IACS, Ave San Juan Bosco 13, E-50009 Zaragoza, Spain
[3] Univ Zaragoza, Dept Pharmacol & Physiol, Pedro Cerbuna 12, E-50009 Zaragoza, Spain
[4] Univ Zaragoza, Dept Surg Gynecol & Obstet, Pedro Cerbuna 12, E-50009 Zaragoza, Spain
[5] Univ Tunis El Manar, Fac Sci Tunis, Dept Biol, Univ Campus El Manar, Tunis 2092, Tunisia
[6] Univ Zaragoza, Dept Appl Phys, Pedro Cerbuna 12, E-50009 Zaragoza, Spain
[7] Lozano Blesa Clin Univ Hosp, Dept Ophthalmol, Ave San Juan Bosco 15, E-50009 Zaragoza, Spain
关键词
Retinitis pigmentosa; Free radicals; Antioxidants; Systemic oxidative stress; CONE CELL-DEATH; RETINITIS-PIGMENTOSA; LIPID-PEROXIDATION; EPITHELIAL-CELLS; ANIMAL-MODEL; GLUTATHIONE; PATHWAYS; MECHANISMS; MICROGLIA; MUTATION;
D O I
10.1016/j.freeradbiomed.2018.07.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Retinitis pigmentosa (RP) comprises a group of inherited retinal degenerative conditions characterized by primary degeneration of the rod photoreceptors. Increased oxidative damage is observed in the retina, aqueous humor, and plasma of RP animal models and patients. The hepatic oxidative status may also be affected in RP due to oxidative damage influencing soluble macromolecules exiting the retina or to alterations in the melanopsin system resulting in chronic circadian desynchronization that negatively alters the oxidative stress defense system. P23H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical conditions of RP. We measured hepatic malondialdehyde and 4-hydroxyalkenal concentrations as oxidative stress markers; nitrite level as a total nitrosative damage marker; total antioxidant capacity; and the activities of catalase, superoxide dismutase (SOD), and glutathione S-transferase. Retinal visual function was assessed based on optomotor and electroretinogram responses. P23H transgenic rats exhibited diminished visual acuity, contrast sensitivity, and electroretinographic responses according to the level of retinal degeneration. P23H rats at 30 days of age already demonstrated only 47% of the hepatic total antioxidant capacity of wild-type animals. Hepatic catalase and SOD activities were also reduced in P23H rats after 120 days, but we detected no difference in glutathione S-transferase activity. P23H rats had increased hepatic oxidative and nitrosative damage markers. GSH/GSSG ratio showed a significant diminution in P23H rats at P120 compared to WT. We conclude that the liver is under increased oxidative stress in P23H rats. Further studies are required, however, to clarify the contribution of systemic oxidative damage to the pathogenesis of RP.
引用
收藏
页码:550 / 557
页数:8
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